Leslie S. Baumann, MD

During the last 25 years, green tea, which is derived from Camellia sinensis (an evergreen member of the Theaceae family), has gained considerable attention because of its purported antioxidant and anticarcinogenic properties. Believed to have been used by human beings for 4,000 years,¹ green tea is now one of the most heavily researched of the antioxidants, with numerous studies of its cutaneous effects appearing in the literature.² Laden with plant polyphenols, orally administered or topically applied green tea has been shown to display significant antioxidant, chemopreventive, immunomodulatory, and anti-inflammatory activity, affecting the biochemical pathways important in cell proliferation.^3-6 For this reason, and due to its global popularity as a beverage, green tea polyphenols are among the most frequently studied herbal agents used in medicine.

Polyphenols, many of which are potent antioxidants, are a large diverse family of thousands of chemical compounds present in plants. The four major polyphenolic catechins present in green tea include: ECG [(-)EpiCatechin-3-O-Gallate], GCG [(-)GalloCatechin-3-O-Gallate], EGC [(-)EpiGalloCatechin], and EGCG [(-)EpiGalloCatechin-3-O-Gallate], the most abundant and biologically active green tea constituent. In fact, EGCG is the component associated with the greatest anticarcinogenic and chemopreventive properties.⁶

A wide-ranging evidence-based review of the use of botanicals in dermatology, published in 2010, showed that the oral administration, in particular, as well as topical application of antioxidant plant extracts of green tea, among other botanicals, can protect skin against the harmful effects of UV exposure, including erythema, premature aging, and cancer.⁷

Green tea is thought to be challenging to formulate because of the inherent hydrophilicity of EGCG, which limits penetration into human skin.^8,9 Nevertheless, green tea is thought to have great potential in traditional sunscreens to enhance photoprotection.^10,11 The photoprotective activity of orally administered or topically applied green tea has been supported in various studies.^12-15

The remainder of this column will focus on recent studies of topically applied green tea polyphenols in human beings as well as clinical uses of this agent.

Topical uses

Topical green tea appears to reduce skin inflammation and neutralize free radicals, which explains its popularity as an additive in rosacea and antiaging skin care products. The antiaging effects of green tea are difficult to measure because it functions as an antioxidant that prevents aging and does not have the capacity to increase collagen synthesis or ameliorate already existing wrinkles. However, there is relatively good evidence, in comparison to other antioxidants, suggesting that topically applied green tea can help protect skin from UV radiation.¹⁶

Investigators performed a thorough literature search of all in vitro, in vivo, and controlled clinical trials involving green tea formulations and their dermatologic applications, which was published in 2012. They evaluated 20 studies, with evidence suggesting that orally administered green tea displays a broad range of healthy activity, and supportive data for the use of topically applied green tea extract for treatment of various cutaneous conditions, including acne, rosacea, atopic dermatitis, androgenetic alopecia, hirsutism, candidiasis, keloids, leishmaniasis, and genital warts.¹⁷

Also, a green tea topical formulation, green tea sinecatechin Polyphenon E (Veregen) ointment, has recently been shown to exert antioxidant, antiviral, and antitumor activity, and has demonstrated efficacy in treating Condylomata acuminata (external anogenital warts).¹⁸ In addition, topically applying green tea catechins in the morning in combination with traditional sunscreens is believed to have the potential to protect the skin from UV-induced damage. Topical green tea may improve rosacea, prevent retinoid dermatitis, and play a role in managing pigmentation disorders. Few of the many over-the-counter products that contain green tea catechins have been tested in controlled clinical trials and the concentration of polyphenols in these products is too low to demonstrate efficacy. It is necessary to know the amount of green tea catechins in a formulation to judge its efficacy.

Acne

In 2009, in a 6-week study investigating the efficacy of 2% green tea lotion for the treatment of mild-to-moderate acne vulgaris in 20 patients, researchers reported statistically significant reductions in mean total lesion count and mean severity index (devised by the authors to correlate with total lesion count in increasing intensity, scaled from 1 to 3). They concluded that 2% green tea lotion is both an effective and cost effective approach for treating mild-to-moderate acne lesions.¹⁹

A 2012 study revealed that ethanol extracts of several herbs, including green tea, exhibited the potential for inhibiting acne when incorporated into a topical moisturizer, specifically acting against acne-causing bacteria without provoking irritation.²⁰ Earlier that year, other investigators conducted in vitro and in vivo experiments to evaluate the effects against acne of polyphenon-60, which contains various green tea catechins (now referred to as sinecatechins in the United States.).²¹ In this clinical study, patients exhibited improvement in acne symptoms, including a reduction in the number of pustules and comedones.²²

A study published in 2013, a single-blind, placebo-controlled, split-face comparative study in 22 individuals over 60 days, evaluated the efficacy of green tea, as well as green tea plus lotus, compared with placebo for controlling casual sebum secretions in healthy adults. Compared with placebo, consistent and statistically significant decreases in sebum secretions were observed in both treatment groups. The combination of green tea and lotus extracts also achieved statistically sounder results than green tea alone. The investigators concluded that a synergistic interaction between green tea and lotus extract constituents appears to hold promise for the treatment of skin conditions in which elevated sebum levels are involved.²³

Anogenital warts

In 2006, the Food and Drug Administration approved for the first time a botanical drug formulation for the topical treatment of genital and perianal warts: sinecatechins, derived from green tea catechins and other C. sinensis constituents in a topical 15% ointment (Veregen).^{21, 24-28}

Two years later, Tatti et al. conducted a randomized, double-blind, vehicle-controlled trial to evaluate the efficacy of topical sinecatechins in 502 male and female patients (aged 18 years and older) for the treatment of anogenital warts. For 16 weeks or until complete clearance, subjects applied sinecatechins ointment 15% or 10% or vehicle (placebo) three times daily. Complete clearance was achieved in 57.2% of patients treated with 15% ointment, 56.3% using 10% ointment, and 33.7% who used only the vehicle. Respective recurrence rates, after 12 weeks, were 6.5%, 8.3%, and 8.8%. The investigators concluded that topical sinecatechins in 15% and 10% concentrations represent effective and well-tolerated options for anogenital wart treatment.²⁹

Similarly favorable results regarding polyphenon E 15% were reported in reference to three placebo-controlled clinical studies in 1,400 patients with genital warts from Europe, North and South America, and South Africa,^30,31 and by Tatti et al. again in 2010 after randomized, double-blind, vehicle-controlled safety and efficacy trials in nearly 1,000 patients treated with polyphenon E 15% and 10% formulations.²¹

Two years later, investigators evaluated sinecatechins (Polyphenon E) 10% ointment in two double-blind, multinational studies in adults with external genital and perianal warts. Polyphenon E 10% was found to be significantly more effective than vehicle in completely or partially clearing all warts.³²

Earlier that year, a review of the use of sinecatechins ointment for the treatment of external anogenital warts noted that while clearance rates are similar among sinecatechins and other indicated topical medications such as imiquimod and podophyllotoxin, recurrence rates are lower for patients treated with sinecatechins. The authors concluded that the use of sinecatechins for condylomata acuminata was safe and effective and its various molecular activities suggest broader applications to other viral and tumor lesions.³³

In 2015, Gupta and Daigle reported that sinecatechins 10% ointment for the treatment of external genital warts was found in phase III trials to display greater efficacy and lower rates of recurrence in comparison to patient-applied treatments now available.²⁸ Later that year, in a systematic PubMed and Embase review of clinical trials involving the use of polyphenol-based therapies, Tuong et al. identified cogent evidence suggesting the effectiveness of green tea polyphenols for the treatment of anogenital warts.³⁴

Antiaging activity

Green tea has been shown to work in combination with red light to exert a rejuvenating effect on the skin, as Sommer and Zhu reported in 2009 that green tea filled cotton pads applied once daily for 20 minutes prior to treatment with light-emitting diodes (central wavelength 670 nm, dermal dose 4 J/cm²) reduced wrinkles in 1 month comparably to 10 months of light treatment alone.³⁵

In 2013, Hong et al. studied the antiwrinkle effects of topically applied green tea extract with high antioxidant activity after tannase treatment. Study participants were randomly divided to receive either green tea extract or tannase-converted green tea extract on their crow’s feet for an 8-week period. The investigators found that tannase treatment elevated the antioxidant activity of green tea and imparted antiwrinkle effects.³⁶

At around the same time, Gianeti conducted clinical studies in 24 volunteers to assess the effects of a cosmetic formulation containing 6% C. sinensis glycolic leaf extracts. Skin moisture was enhanced after 30 days of topical application as was the viscoelastic-to-elastic ratio compared with vehicle and control (a forearm area left untreated). Skin roughness was significantly diminished after 30 days. The investigators concluded that the topical cosmetic formulation with green tea yielded salient moisturizing and cutaneous microrelief benefits.³⁷

Also in 2013, oral intake of green tea catechins in 16 healthy human subjects (with 14 completing the study) appeared to result in the integration of catechin metabolites into human skin linked to the negation of UV-induced 12-hydroxyeicosatetraenoic acid (12-HETE). The investigators speculated that this incorporation of catechins may render protection against sunburn inflammation and even cumulative UV-induced harm.³⁸

After earlier showing the efficacy of green tea and lotus extracts in skin disorders involving excess sebum in a single-blinded, placebo-controlled, split-face comparative study,²³ Mahmood and Akhtar conducted a 60-day placebo-controlled comparative split-face study in 33 healthy Asian men to evaluate the efficacy of two cosmetic formulations (green tea and lotus extract) for facial wrinkles. All of the formulations yielded improvements in skin roughness, scaliness, smoothness, and wrinkling, with the greatest reduction in wrinkling conferred by the combination formulation. The investigators concluded that the synergistic activity of green tea and lotus extracts exerted significant improvement along several skin parameters, suggesting the potential for these ingredients in antiaging products.³⁸

In 2014, the synergistic effects of green tea and ginkgo biloba were explored in preclinical and clinical studies. In the clinical study, 48 participants applied the formulations on forearm skin and were evaluated before and after 3 hours and following 15- and 30-day use periods. Results showed a moisturizing effect and enhancement in skin microrelief, as well as improvements in skin elasticity and barrier function.³

Conclusion

Green tea remains one of the most researched antioxidants as benefits from its use continue to emerge. Indeed, green tea polyphenols are in use for a growing number of indications, especially acne and anogenital warts, and there is reason for optimism that topically applied green tea will gain momentum as an increasingly selected therapeutic option. More clinical studies are necessary to further establish the potential role of green tea for a wider range of cutaneous indications. Green tea holds particular promise in relation to photoprotection against UV-induced skin cancer and skin aging.

Dr. Baumann is chief executive officer of the Baumann Cosmetic & Research Institute in the Design District in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann wrote the textbook “Cosmetic Dermatology: Principles and Practice” (New York: McGraw-Hill, 2002), and a book for consumers, “The Skin Type Solution” (New York: Bantam Dell, 2006). Her latest book, “Cosmeceuticals and Cosmetic Ingredients,” was published in November 2014. Dr. Baumann has received funding for clinical grants from Allergan, Aveeno, Avon Products, Evolus, Galderma, GlaxoSmithKline, Kythera Biopharmaceuticals, Mary Kay, Medicis Pharmaceuticals, Neutrogena, Philosophy, Topix Pharmaceuticals, and Unilever. She also developed and owns the Baumann Skin Type Solution skin typing systems and related products

References:

1. Cancer Lett. 1997 Mar 19;114(1-2):315-7.

2. J Am Acad Dermatol. 2005 Jun;52(6):1049-59.

3. Arch Dermatol. 2000 Aug;136(8):989-94.

4. Photochem Photobiol. 1995 Nov;62(5):855-61.

5. Oxid Med Cell Longev. 2012:2012:560682.

6. J Dtsch Dermatol Ges. 2015 Aug;13(8):768-75.

7. Am J Clin Dermatol. 2010;11(4):247-67.

8. Dermatol Ther. 2007 Sep-Oct;20(5):322-9.

9. J Clin Aesthet Dermatol. 2010 Feb;3(2):22-41.

10. Photodermatol Photoimmunol Photomed. 2007 Feb;23(1):48-56.

11. Skin Res Technol. 2009 Aug;15(3):338-45.

12. Exp Dermatol. 2009 Jan;18(1):69-77.

13. Exp Dermatol. 2009 Jun;18(6):522-6.

14. Arch Biochem Biophys. 2011 Apr 15;508(2):152-8.

15. Cancer Prev Res (Phila). 2010 Feb;3(2):179-89.

16. Complement Ther Clin Pract. 2014 Feb;20(1):11-5.

17. Skinmed. 2012 Nov-Dec;10(6):352-5.

18. J Eur Acad Dermatol Venereol. 2011 Mar;25(3):345-53.

19. J Drugs Dermatol. 2009 Apr;8(4):358-64.

20. Pak J Pharm Sci. 2012 Oct;25(4):867-70.

21. Br J Dermatol. 2010 Jan;162(1):176-84.

22. Arch Dermatol Res. 2012 Oct;304(8):655-63.

23. Hippokratia. 2013 Jan;17(1):64-7.

24. Food Chem Toxicol. 2008 Aug;46(8):2606-10.

25. Nat Biotechnol. 2008 Oct;26(10):1077-83.

26. Skin Therapy Lett. 2012 Apr;17(4):5-7.

27. J Clin Aesthet Dermatol. 2012 Jan;5(1):19-26.

28. Skin Therapy Lett. 2015 Jan-Feb;20(1):6-8.

29. Obstet Gynecol. 2008 Jun;111(6):1371-9.

30. Hautarzt. 2008 Jan;59(1):31-5.

31. J Eur Acad Dermatol Venereol. 2007 Nov;21(10):1404-12.

32. Am J Clin Dermatol. 2012 Aug 1:13(4):275-81.

33. Expert Opin Biol Ther. 2012 Jun;12(6):783-93.

34. J Dermatolog Treat. 2015;26(4):381-8.

35. Photomed Laser Surg. 2009 Dec;27(6):969-71.

36. J Cosmet Dermatol. 2013 Jun;12(2):137-43.

37. Dermatol Ther. 2013 May-Jun;26(3):267-71.

38. Rejuvenation Res. 2013 Apr;16(2):91-7.

39. J Drugs Dermatol. 2014 Sep;13(9):1092-7.

During the last 25 years, green tea, which is derived from Camellia sinensis (an evergreen member of the Theaceae family), has gained considerable attention because of its purported antioxidant and anticarcinogenic properties. Believed to have been used by human beings for 4,000 years,¹ green tea is now one of the most heavily researched of the antioxidants, with numerous studies of its cutaneous effects appearing in the literature.² Laden with plant polyphenols, orally administered or topically applied green tea has been shown to display significant antioxidant, chemopreventive, immunomodulatory, and anti-inflammatory activity, affecting the biochemical pathways important in cell proliferation.^3-6 For this reason, and due to its global popularity as a beverage, green tea polyphenols are among the most frequently studied herbal agents used in medicine.

Polyphenols, many of which are potent antioxidants, are a large diverse family of thousands of chemical compounds present in plants. The four major polyphenolic catechins present in green tea include: ECG [(-)EpiCatechin-3-O-Gallate], GCG [(-)GalloCatechin-3-O-Gallate], EGC [(-)EpiGalloCatechin], and EGCG [(-)EpiGalloCatechin-3-O-Gallate], the most abundant and biologically active green tea constituent. In fact, EGCG is the component associated with the greatest anticarcinogenic and chemopreventive properties.⁶

A wide-ranging evidence-based review of the use of botanicals in dermatology, published in 2010, showed that the oral administration, in particular, as well as topical application of antioxidant plant extracts of green tea, among other botanicals, can protect skin against the harmful effects of UV exposure, including erythema, premature aging, and cancer.⁷

Green tea is thought to be challenging to formulate because of the inherent hydrophilicity of EGCG, which limits penetration into human skin.^8,9 Nevertheless, green tea is thought to have great potential in traditional sunscreens to enhance photoprotection.^10,11 The photoprotective activity of orally administered or topically applied green tea has been supported in various studies.^12-15

The remainder of this column will focus on recent studies of topically applied green tea polyphenols in human beings as well as clinical uses of this agent.

Topical uses

Topical green tea appears to reduce skin inflammation and neutralize free radicals, which explains its popularity as an additive in rosacea and antiaging skin care products. The antiaging effects of green tea are difficult to measure because it functions as an antioxidant that prevents aging and does not have the capacity to increase collagen synthesis or ameliorate already existing wrinkles. However, there is relatively good evidence, in comparison to other antioxidants, suggesting that topically applied green tea can help protect skin from UV radiation.¹⁶

Investigators performed a thorough literature search of all in vitro, in vivo, and controlled clinical trials involving green tea formulations and their dermatologic applications, which was published in 2012. They evaluated 20 studies, with evidence suggesting that orally administered green tea displays a broad range of healthy activity, and supportive data for the use of topically applied green tea extract for treatment of various cutaneous conditions, including acne, rosacea, atopic dermatitis, androgenetic alopecia, hirsutism, candidiasis, keloids, leishmaniasis, and genital warts.¹⁷

Also, a green tea topical formulation, green tea sinecatechin Polyphenon E (Veregen) ointment, has recently been shown to exert antioxidant, antiviral, and antitumor activity, and has demonstrated efficacy in treating Condylomata acuminata (external anogenital warts).¹⁸ In addition, topically applying green tea catechins in the morning in combination with traditional sunscreens is believed to have the potential to protect the skin from UV-induced damage. Topical green tea may improve rosacea, prevent retinoid dermatitis, and play a role in managing pigmentation disorders. Few of the many over-the-counter products that contain green tea catechins have been tested in controlled clinical trials and the concentration of polyphenols in these products is too low to demonstrate efficacy. It is necessary to know the amount of green tea catechins in a formulation to judge its efficacy.

Acne

In 2009, in a 6-week study investigating the efficacy of 2% green tea lotion for the treatment of mild-to-moderate acne vulgaris in 20 patients, researchers reported statistically significant reductions in mean total lesion count and mean severity index (devised by the authors to correlate with total lesion count in increasing intensity, scaled from 1 to 3). They concluded that 2% green tea lotion is both an effective and cost effective approach for treating mild-to-moderate acne lesions.¹⁹

A 2012 study revealed that ethanol extracts of several herbs, including green tea, exhibited the potential for inhibiting acne when incorporated into a topical moisturizer, specifically acting against acne-causing bacteria without provoking irritation.²⁰ Earlier that year, other investigators conducted in vitro and in vivo experiments to evaluate the effects against acne of polyphenon-60, which contains various green tea catechins (now referred to as sinecatechins in the United States.).²¹ In this clinical study, patients exhibited improvement in acne symptoms, including a reduction in the number of pustules and comedones.²²

A study published in 2013, a single-blind, placebo-controlled, split-face comparative study in 22 individuals over 60 days, evaluated the efficacy of green tea, as well as green tea plus lotus, compared with placebo for controlling casual sebum secretions in healthy adults. Compared with placebo, consistent and statistically significant decreases in sebum secretions were observed in both treatment groups. The combination of green tea and lotus extracts also achieved statistically sounder results than green tea alone. The investigators concluded that a synergistic interaction between green tea and lotus extract constituents appears to hold promise for the treatment of skin conditions in which elevated sebum levels are involved.²³

Anogenital warts

In 2006, the Food and Drug Administration approved for the first time a botanical drug formulation for the topical treatment of genital and perianal warts: sinecatechins, derived from green tea catechins and other C. sinensis constituents in a topical 15% ointment (Veregen).^{21, 24-28}

Two years later, Tatti et al. conducted a randomized, double-blind, vehicle-controlled trial to evaluate the efficacy of topical sinecatechins in 502 male and female patients (aged 18 years and older) for the treatment of anogenital warts. For 16 weeks or until complete clearance, subjects applied sinecatechins ointment 15% or 10% or vehicle (placebo) three times daily. Complete clearance was achieved in 57.2% of patients treated with 15% ointment, 56.3% using 10% ointment, and 33.7% who used only the vehicle. Respective recurrence rates, after 12 weeks, were 6.5%, 8.3%, and 8.8%. The investigators concluded that topical sinecatechins in 15% and 10% concentrations represent effective and well-tolerated options for anogenital wart treatment.²⁹

Similarly favorable results regarding polyphenon E 15% were reported in reference to three placebo-controlled clinical studies in 1,400 patients with genital warts from Europe, North and South America, and South Africa,^30,31 and by Tatti et al. again in 2010 after randomized, double-blind, vehicle-controlled safety and efficacy trials in nearly 1,000 patients treated with polyphenon E 15% and 10% formulations.²¹

Two years later, investigators evaluated sinecatechins (Polyphenon E) 10% ointment in two double-blind, multinational studies in adults with external genital and perianal warts. Polyphenon E 10% was found to be significantly more effective than vehicle in completely or partially clearing all warts.³²

Earlier that year, a review of the use of sinecatechins ointment for the treatment of external anogenital warts noted that while clearance rates are similar among sinecatechins and other indicated topical medications such as imiquimod and podophyllotoxin, recurrence rates are lower for patients treated with sinecatechins. The authors concluded that the use of sinecatechins for condylomata acuminata was safe and effective and its various molecular activities suggest broader applications to other viral and tumor lesions.³³

In 2015, Gupta and Daigle reported that sinecatechins 10% ointment for the treatment of external genital warts was found in phase III trials to display greater efficacy and lower rates of recurrence in comparison to patient-applied treatments now available.²⁸ Later that year, in a systematic PubMed and Embase review of clinical trials involving the use of polyphenol-based therapies, Tuong et al. identified cogent evidence suggesting the effectiveness of green tea polyphenols for the treatment of anogenital warts.³⁴

Antiaging activity

Green tea has been shown to work in combination with red light to exert a rejuvenating effect on the skin, as Sommer and Zhu reported in 2009 that green tea filled cotton pads applied once daily for 20 minutes prior to treatment with light-emitting diodes (central wavelength 670 nm, dermal dose 4 J/cm²) reduced wrinkles in 1 month comparably to 10 months of light treatment alone.³⁵

In 2013, Hong et al. studied the antiwrinkle effects of topically applied green tea extract with high antioxidant activity after tannase treatment. Study participants were randomly divided to receive either green tea extract or tannase-converted green tea extract on their crow’s feet for an 8-week period. The investigators found that tannase treatment elevated the antioxidant activity of green tea and imparted antiwrinkle effects.³⁶

At around the same time, Gianeti conducted clinical studies in 24 volunteers to assess the effects of a cosmetic formulation containing 6% C. sinensis glycolic leaf extracts. Skin moisture was enhanced after 30 days of topical application as was the viscoelastic-to-elastic ratio compared with vehicle and control (a forearm area left untreated). Skin roughness was significantly diminished after 30 days. The investigators concluded that the topical cosmetic formulation with green tea yielded salient moisturizing and cutaneous microrelief benefits.³⁷

Also in 2013, oral intake of green tea catechins in 16 healthy human subjects (with 14 completing the study) appeared to result in the integration of catechin metabolites into human skin linked to the negation of UV-induced 12-hydroxyeicosatetraenoic acid (12-HETE). The investigators speculated that this incorporation of catechins may render protection against sunburn inflammation and even cumulative UV-induced harm.³⁸

After earlier showing the efficacy of green tea and lotus extracts in skin disorders involving excess sebum in a single-blinded, placebo-controlled, split-face comparative study,²³ Mahmood and Akhtar conducted a 60-day placebo-controlled comparative split-face study in 33 healthy Asian men to evaluate the efficacy of two cosmetic formulations (green tea and lotus extract) for facial wrinkles. All of the formulations yielded improvements in skin roughness, scaliness, smoothness, and wrinkling, with the greatest reduction in wrinkling conferred by the combination formulation. The investigators concluded that the synergistic activity of green tea and lotus extracts exerted significant improvement along several skin parameters, suggesting the potential for these ingredients in antiaging products.³⁸

In 2014, the synergistic effects of green tea and ginkgo biloba were explored in preclinical and clinical studies. In the clinical study, 48 participants applied the formulations on forearm skin and were evaluated before and after 3 hours and following 15- and 30-day use periods. Results showed a moisturizing effect and enhancement in skin microrelief, as well as improvements in skin elasticity and barrier function.³

Conclusion

Green tea remains one of the most researched antioxidants as benefits from its use continue to emerge. Indeed, green tea polyphenols are in use for a growing number of indications, especially acne and anogenital warts, and there is reason for optimism that topically applied green tea will gain momentum as an increasingly selected therapeutic option. More clinical studies are necessary to further establish the potential role of green tea for a wider range of cutaneous indications. Green tea holds particular promise in relation to photoprotection against UV-induced skin cancer and skin aging.

Dr. Baumann is chief executive officer of the Baumann Cosmetic & Research Institute in the Design District in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann wrote the textbook “Cosmetic Dermatology: Principles and Practice” (New York: McGraw-Hill, 2002), and a book for consumers, “The Skin Type Solution” (New York: Bantam Dell, 2006). Her latest book, “Cosmeceuticals and Cosmetic Ingredients,” was published in November 2014. Dr. Baumann has received funding for clinical grants from Allergan, Aveeno, Avon Products, Evolus, Galderma, GlaxoSmithKline, Kythera Biopharmaceuticals, Mary Kay, Medicis Pharmaceuticals, Neutrogena, Philosophy, Topix Pharmaceuticals, and Unilever. She also developed and owns the Baumann Skin Type Solution skin typing systems and related products

References:

1. Cancer Lett. 1997 Mar 19;114(1-2):315-7.

2. J Am Acad Dermatol. 2005 Jun;52(6):1049-59.

3. Arch Dermatol. 2000 Aug;136(8):989-94.

4. Photochem Photobiol. 1995 Nov;62(5):855-61.

5. Oxid Med Cell Longev. 2012:2012:560682.

6. J Dtsch Dermatol Ges. 2015 Aug;13(8):768-75.

7. Am J Clin Dermatol. 2010;11(4):247-67.

8. Dermatol Ther. 2007 Sep-Oct;20(5):322-9.

9. J Clin Aesthet Dermatol. 2010 Feb;3(2):22-41.

10. Photodermatol Photoimmunol Photomed. 2007 Feb;23(1):48-56.

11. Skin Res Technol. 2009 Aug;15(3):338-45.

12. Exp Dermatol. 2009 Jan;18(1):69-77.

13. Exp Dermatol. 2009 Jun;18(6):522-6.

14. Arch Biochem Biophys. 2011 Apr 15;508(2):152-8.

15. Cancer Prev Res (Phila). 2010 Feb;3(2):179-89.

16. Complement Ther Clin Pract. 2014 Feb;20(1):11-5.

17. Skinmed. 2012 Nov-Dec;10(6):352-5.

18. J Eur Acad Dermatol Venereol. 2011 Mar;25(3):345-53.

19. J Drugs Dermatol. 2009 Apr;8(4):358-64.

20. Pak J Pharm Sci. 2012 Oct;25(4):867-70.

21. Br J Dermatol. 2010 Jan;162(1):176-84.

22. Arch Dermatol Res. 2012 Oct;304(8):655-63.

23. Hippokratia. 2013 Jan;17(1):64-7.

24. Food Chem Toxicol. 2008 Aug;46(8):2606-10.

25. Nat Biotechnol. 2008 Oct;26(10):1077-83.

26. Skin Therapy Lett. 2012 Apr;17(4):5-7.

27. J Clin Aesthet Dermatol. 2012 Jan;5(1):19-26.

28. Skin Therapy Lett. 2015 Jan-Feb;20(1):6-8.

29. Obstet Gynecol. 2008 Jun;111(6):1371-9.

30. Hautarzt. 2008 Jan;59(1):31-5.

31. J Eur Acad Dermatol Venereol. 2007 Nov;21(10):1404-12.

32. Am J Clin Dermatol. 2012 Aug 1:13(4):275-81.

33. Expert Opin Biol Ther. 2012 Jun;12(6):783-93.

34. J Dermatolog Treat. 2015;26(4):381-8.

35. Photomed Laser Surg. 2009 Dec;27(6):969-71.

36. J Cosmet Dermatol. 2013 Jun;12(2):137-43.

37. Dermatol Ther. 2013 May-Jun;26(3):267-71.

38. Rejuvenation Res. 2013 Apr;16(2):91-7.

39. J Drugs Dermatol. 2014 Sep;13(9):1092-7.

During the last 25 years, green tea, which is derived from Camellia sinensis (an evergreen member of the Theaceae family), has gained considerable attention because of its purported antioxidant and anticarcinogenic properties. Believed to have been used by human beings for 4,000 years,¹ green tea is now one of the most heavily researched of the antioxidants, with numerous studies of its cutaneous effects appearing in the literature.² Laden with plant polyphenols, orally administered or topically applied green tea has been shown to display significant antioxidant, chemopreventive, immunomodulatory, and anti-inflammatory activity, affecting the biochemical pathways important in cell proliferation.^3-6 For this reason, and due to its global popularity as a beverage, green tea polyphenols are among the most frequently studied herbal agents used in medicine.

Polyphenols, many of which are potent antioxidants, are a large diverse family of thousands of chemical compounds present in plants. The four major polyphenolic catechins present in green tea include: ECG [(-)EpiCatechin-3-O-Gallate], GCG [(-)GalloCatechin-3-O-Gallate], EGC [(-)EpiGalloCatechin], and EGCG [(-)EpiGalloCatechin-3-O-Gallate], the most abundant and biologically active green tea constituent. In fact, EGCG is the component associated with the greatest anticarcinogenic and chemopreventive properties.⁶

A wide-ranging evidence-based review of the use of botanicals in dermatology, published in 2010, showed that the oral administration, in particular, as well as topical application of antioxidant plant extracts of green tea, among other botanicals, can protect skin against the harmful effects of UV exposure, including erythema, premature aging, and cancer.⁷

Green tea is thought to be challenging to formulate because of the inherent hydrophilicity of EGCG, which limits penetration into human skin.^8,9 Nevertheless, green tea is thought to have great potential in traditional sunscreens to enhance photoprotection.^10,11 The photoprotective activity of orally administered or topically applied green tea has been supported in various studies.^12-15

The remainder of this column will focus on recent studies of topically applied green tea polyphenols in human beings as well as clinical uses of this agent.

Topical uses

Topical green tea appears to reduce skin inflammation and neutralize free radicals, which explains its popularity as an additive in rosacea and antiaging skin care products. The antiaging effects of green tea are difficult to measure because it functions as an antioxidant that prevents aging and does not have the capacity to increase collagen synthesis or ameliorate already existing wrinkles. However, there is relatively good evidence, in comparison to other antioxidants, suggesting that topically applied green tea can help protect skin from UV radiation.¹⁶

Investigators performed a thorough literature search of all in vitro, in vivo, and controlled clinical trials involving green tea formulations and their dermatologic applications, which was published in 2012. They evaluated 20 studies, with evidence suggesting that orally administered green tea displays a broad range of healthy activity, and supportive data for the use of topically applied green tea extract for treatment of various cutaneous conditions, including acne, rosacea, atopic dermatitis, androgenetic alopecia, hirsutism, candidiasis, keloids, leishmaniasis, and genital warts.¹⁷

Also, a green tea topical formulation, green tea sinecatechin Polyphenon E (Veregen) ointment, has recently been shown to exert antioxidant, antiviral, and antitumor activity, and has demonstrated efficacy in treating Condylomata acuminata (external anogenital warts).¹⁸ In addition, topically applying green tea catechins in the morning in combination with traditional sunscreens is believed to have the potential to protect the skin from UV-induced damage. Topical green tea may improve rosacea, prevent retinoid dermatitis, and play a role in managing pigmentation disorders. Few of the many over-the-counter products that contain green tea catechins have been tested in controlled clinical trials and the concentration of polyphenols in these products is too low to demonstrate efficacy. It is necessary to know the amount of green tea catechins in a formulation to judge its efficacy.

Acne

In 2009, in a 6-week study investigating the efficacy of 2% green tea lotion for the treatment of mild-to-moderate acne vulgaris in 20 patients, researchers reported statistically significant reductions in mean total lesion count and mean severity index (devised by the authors to correlate with total lesion count in increasing intensity, scaled from 1 to 3). They concluded that 2% green tea lotion is both an effective and cost effective approach for treating mild-to-moderate acne lesions.¹⁹

A 2012 study revealed that ethanol extracts of several herbs, including green tea, exhibited the potential for inhibiting acne when incorporated into a topical moisturizer, specifically acting against acne-causing bacteria without provoking irritation.²⁰ Earlier that year, other investigators conducted in vitro and in vivo experiments to evaluate the effects against acne of polyphenon-60, which contains various green tea catechins (now referred to as sinecatechins in the United States.).²¹ In this clinical study, patients exhibited improvement in acne symptoms, including a reduction in the number of pustules and comedones.²²

A study published in 2013, a single-blind, placebo-controlled, split-face comparative study in 22 individuals over 60 days, evaluated the efficacy of green tea, as well as green tea plus lotus, compared with placebo for controlling casual sebum secretions in healthy adults. Compared with placebo, consistent and statistically significant decreases in sebum secretions were observed in both treatment groups. The combination of green tea and lotus extracts also achieved statistically sounder results than green tea alone. The investigators concluded that a synergistic interaction between green tea and lotus extract constituents appears to hold promise for the treatment of skin conditions in which elevated sebum levels are involved.²³

Anogenital warts

In 2006, the Food and Drug Administration approved for the first time a botanical drug formulation for the topical treatment of genital and perianal warts: sinecatechins, derived from green tea catechins and other C. sinensis constituents in a topical 15% ointment (Veregen).^{21, 24-28}

Two years later, Tatti et al. conducted a randomized, double-blind, vehicle-controlled trial to evaluate the efficacy of topical sinecatechins in 502 male and female patients (aged 18 years and older) for the treatment of anogenital warts. For 16 weeks or until complete clearance, subjects applied sinecatechins ointment 15% or 10% or vehicle (placebo) three times daily. Complete clearance was achieved in 57.2% of patients treated with 15% ointment, 56.3% using 10% ointment, and 33.7% who used only the vehicle. Respective recurrence rates, after 12 weeks, were 6.5%, 8.3%, and 8.8%. The investigators concluded that topical sinecatechins in 15% and 10% concentrations represent effective and well-tolerated options for anogenital wart treatment.²⁹

Similarly favorable results regarding polyphenon E 15% were reported in reference to three placebo-controlled clinical studies in 1,400 patients with genital warts from Europe, North and South America, and South Africa,^30,31 and by Tatti et al. again in 2010 after randomized, double-blind, vehicle-controlled safety and efficacy trials in nearly 1,000 patients treated with polyphenon E 15% and 10% formulations.²¹

Two years later, investigators evaluated sinecatechins (Polyphenon E) 10% ointment in two double-blind, multinational studies in adults with external genital and perianal warts. Polyphenon E 10% was found to be significantly more effective than vehicle in completely or partially clearing all warts.³²

Earlier that year, a review of the use of sinecatechins ointment for the treatment of external anogenital warts noted that while clearance rates are similar among sinecatechins and other indicated topical medications such as imiquimod and podophyllotoxin, recurrence rates are lower for patients treated with sinecatechins. The authors concluded that the use of sinecatechins for condylomata acuminata was safe and effective and its various molecular activities suggest broader applications to other viral and tumor lesions.³³

In 2015, Gupta and Daigle reported that sinecatechins 10% ointment for the treatment of external genital warts was found in phase III trials to display greater efficacy and lower rates of recurrence in comparison to patient-applied treatments now available.²⁸ Later that year, in a systematic PubMed and Embase review of clinical trials involving the use of polyphenol-based therapies, Tuong et al. identified cogent evidence suggesting the effectiveness of green tea polyphenols for the treatment of anogenital warts.³⁴

Antiaging activity

Green tea has been shown to work in combination with red light to exert a rejuvenating effect on the skin, as Sommer and Zhu reported in 2009 that green tea filled cotton pads applied once daily for 20 minutes prior to treatment with light-emitting diodes (central wavelength 670 nm, dermal dose 4 J/cm²) reduced wrinkles in 1 month comparably to 10 months of light treatment alone.³⁵

In 2013, Hong et al. studied the antiwrinkle effects of topically applied green tea extract with high antioxidant activity after tannase treatment. Study participants were randomly divided to receive either green tea extract or tannase-converted green tea extract on their crow’s feet for an 8-week period. The investigators found that tannase treatment elevated the antioxidant activity of green tea and imparted antiwrinkle effects.³⁶

At around the same time, Gianeti conducted clinical studies in 24 volunteers to assess the effects of a cosmetic formulation containing 6% C. sinensis glycolic leaf extracts. Skin moisture was enhanced after 30 days of topical application as was the viscoelastic-to-elastic ratio compared with vehicle and control (a forearm area left untreated). Skin roughness was significantly diminished after 30 days. The investigators concluded that the topical cosmetic formulation with green tea yielded salient moisturizing and cutaneous microrelief benefits.³⁷

Also in 2013, oral intake of green tea catechins in 16 healthy human subjects (with 14 completing the study) appeared to result in the integration of catechin metabolites into human skin linked to the negation of UV-induced 12-hydroxyeicosatetraenoic acid (12-HETE). The investigators speculated that this incorporation of catechins may render protection against sunburn inflammation and even cumulative UV-induced harm.³⁸

After earlier showing the efficacy of green tea and lotus extracts in skin disorders involving excess sebum in a single-blinded, placebo-controlled, split-face comparative study,²³ Mahmood and Akhtar conducted a 60-day placebo-controlled comparative split-face study in 33 healthy Asian men to evaluate the efficacy of two cosmetic formulations (green tea and lotus extract) for facial wrinkles. All of the formulations yielded improvements in skin roughness, scaliness, smoothness, and wrinkling, with the greatest reduction in wrinkling conferred by the combination formulation. The investigators concluded that the synergistic activity of green tea and lotus extracts exerted significant improvement along several skin parameters, suggesting the potential for these ingredients in antiaging products.³⁸

In 2014, the synergistic effects of green tea and ginkgo biloba were explored in preclinical and clinical studies. In the clinical study, 48 participants applied the formulations on forearm skin and were evaluated before and after 3 hours and following 15- and 30-day use periods. Results showed a moisturizing effect and enhancement in skin microrelief, as well as improvements in skin elasticity and barrier function.³

Conclusion

Green tea remains one of the most researched antioxidants as benefits from its use continue to emerge. Indeed, green tea polyphenols are in use for a growing number of indications, especially acne and anogenital warts, and there is reason for optimism that topically applied green tea will gain momentum as an increasingly selected therapeutic option. More clinical studies are necessary to further establish the potential role of green tea for a wider range of cutaneous indications. Green tea holds particular promise in relation to photoprotection against UV-induced skin cancer and skin aging.

Dr. Baumann is chief executive officer of the Baumann Cosmetic & Research Institute in the Design District in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann wrote the textbook “Cosmetic Dermatology: Principles and Practice” (New York: McGraw-Hill, 2002), and a book for consumers, “The Skin Type Solution” (New York: Bantam Dell, 2006). Her latest book, “Cosmeceuticals and Cosmetic Ingredients,” was published in November 2014. Dr. Baumann has received funding for clinical grants from Allergan, Aveeno, Avon Products, Evolus, Galderma, GlaxoSmithKline, Kythera Biopharmaceuticals, Mary Kay, Medicis Pharmaceuticals, Neutrogena, Philosophy, Topix Pharmaceuticals, and Unilever. She also developed and owns the Baumann Skin Type Solution skin typing systems and related products

References:

1. Cancer Lett. 1997 Mar 19;114(1-2):315-7.

2. J Am Acad Dermatol. 2005 Jun;52(6):1049-59.

3. Arch Dermatol. 2000 Aug;136(8):989-94.

4. Photochem Photobiol. 1995 Nov;62(5):855-61.

5. Oxid Med Cell Longev. 2012:2012:560682.

6. J Dtsch Dermatol Ges. 2015 Aug;13(8):768-75.

7. Am J Clin Dermatol. 2010;11(4):247-67.

8. Dermatol Ther. 2007 Sep-Oct;20(5):322-9.

9. J Clin Aesthet Dermatol. 2010 Feb;3(2):22-41.

10. Photodermatol Photoimmunol Photomed. 2007 Feb;23(1):48-56.

11. Skin Res Technol. 2009 Aug;15(3):338-45.

12. Exp Dermatol. 2009 Jan;18(1):69-77.

13. Exp Dermatol. 2009 Jun;18(6):522-6.

14. Arch Biochem Biophys. 2011 Apr 15;508(2):152-8.

15. Cancer Prev Res (Phila). 2010 Feb;3(2):179-89.

16. Complement Ther Clin Pract. 2014 Feb;20(1):11-5.

17. Skinmed. 2012 Nov-Dec;10(6):352-5.

18. J Eur Acad Dermatol Venereol. 2011 Mar;25(3):345-53.

19. J Drugs Dermatol. 2009 Apr;8(4):358-64.

20. Pak J Pharm Sci. 2012 Oct;25(4):867-70.

21. Br J Dermatol. 2010 Jan;162(1):176-84.

22. Arch Dermatol Res. 2012 Oct;304(8):655-63.

23. Hippokratia. 2013 Jan;17(1):64-7.

24. Food Chem Toxicol. 2008 Aug;46(8):2606-10.

25. Nat Biotechnol. 2008 Oct;26(10):1077-83.

26. Skin Therapy Lett. 2012 Apr;17(4):5-7.

27. J Clin Aesthet Dermatol. 2012 Jan;5(1):19-26.

28. Skin Therapy Lett. 2015 Jan-Feb;20(1):6-8.

29. Obstet Gynecol. 2008 Jun;111(6):1371-9.

30. Hautarzt. 2008 Jan;59(1):31-5.

31. J Eur Acad Dermatol Venereol. 2007 Nov;21(10):1404-12.

32. Am J Clin Dermatol. 2012 Aug 1:13(4):275-81.

33. Expert Opin Biol Ther. 2012 Jun;12(6):783-93.

34. J Dermatolog Treat. 2015;26(4):381-8.

35. Photomed Laser Surg. 2009 Dec;27(6):969-71.

36. J Cosmet Dermatol. 2013 Jun;12(2):137-43.

37. Dermatol Ther. 2013 May-Jun;26(3):267-71.

38. Rejuvenation Res. 2013 Apr;16(2):91-7.

39. J Drugs Dermatol. 2014 Sep;13(9):1092-7.

The ethics behind selling skin care products to patients has been hotly debated within the field of cosmetic dermatology for several decades. In 15 years of practice, I have come to the conclusion that patients want you to and need you to because otherwise they are easily taken advantage of. Other physicians are doing it but we – the dermatologists – are the most qualified to offer skin care advice. This article will discuss the reasons that you need to get over the ethical dilemma and offer skin care to your patients.

Using the correct skin care regimen for the face and body will improve outcomes

Whether a patient suffers from acne, rosacea, melasma, psoriasis, eczema, contact dermatitis, or even tinea versicolor, using the proper skin care regimen will improve outcomes by affecting the skin barrier, pH, hydration level, and function of the keratinocytes and fibroblasts. In fact, every personal care product that touches the skin has an impact on skin health. For example, if a patient uses a detergent-laden bar soap, the skin barrier will be impaired, which can cause them to react to allergens and irritants. Personal care products can affect the skin pH; this is shown to play a role in Malassezia colonization in atopic dermatitis patients (J Clin Med. 2015;4[6]:1217-28). As dermatologists, we know better than anyone that daily use of SPF improves skin health and lowers the risk of postinflammatory pigmentation. We all agree that patients should cleanse the skin and apply a SPF every day. Giving them guidance about which to choose is very important.

Giving the patient exact instructions will lead to improved compliance

Why should recommending skin care products be perceived differently than prescribing a prescription medication? We should prescribe to our patients in writing the exact skin care regimen they should use for their face or body to ensure that they understand the directions. I have been surprised by patients who have said, “I did not know I was supposed to wash my cleanser off,” or “I wash my face with hand soap.” We can help them by educating them and giving them specific instructions. Improved education and communication results in increased compliance. When you do surgery on a wound, you probably tell them to apply a topical antibiotic ointment, but do you direct them to what cleanser to use or tell them which SPF to use on the stitched wound? Providing written instructions for all dermatologic disorders and postprocedure care is necessary to improve compliance and outcomes.

Combine cosmeceuticals, prescription medications, and medical procedures

You (unlike the cosmetic counter salesperson) have the ability to combine cosmeceuticals with prescription medications and medical procedures. In fact, selling your patients the right skin care products to use after a procedure saves them a trip to the store and ensures that they use the correct products. Of course it makes sense that patients getting toxins and fillers should use a retinoid to improve skin aging; however, many general dermatologic diseases would improve with the proper skin care. For example, do you use biologics for psoriasis? Using the proper skin care to regulate skin pH and improve the skin barrier may help prevent colonization of yeast, fungus, and bacteria. The same is true for atopic patients. Do you use liquid nitrogen? Studies show that using a retinoid before a procedure speeds healing. Skin care goes way beyond wrinkles and dark circles under the eyes, so if you are not prescribing the patient an exact regimen, you are not maximizing outcomes.

I don’t have time to talk to my patients about skin care

The missing piece is that most of us don’t have the time to spend discussing skin care. This is where using a standardized scientific methodology is crucial. I developed and use a skin typing methodology in my office and have seen improved physician/patient relationships and increased patient satisfaction resulting in a significant amount of referrals. We also have noted decreased call backs and fewer adverse events from products because the patients have a better understanding of how to properly apply the cosmeceuticals and prescription products. The best part is, it does not add any time onto the patient visit when standardized methodologies are properly adopted.

What if I still do not feel comfortable profiting from the sale of skin care products?

First you need to realize that time is money and you are saving the patient the cost in time it would have taken them to go to a store, park, and shop for the correct product. I have seen data presented from several companies that show that patients usually spend a large amount of money on skin care products after they see their dermatologist. Without guidance, they will likely buy the incorrect products. If they buy the wrong product, you save them the hassle of having to make another office visit and the aggravation of the side effects from the incorrect product. These are often of poor quality or not appropriate for their skin issues. Counterfeit products are rampant on the Internet and many new companies tout worthless products with stem cells and other nonsense. Only you can help your patients make sure that money is spent on the proper products.

Conclusion

Do you really want someone else giving your patients skin care advice? Your patients deserve to have someone with your insights, knowledge, compassion, and honesty help them achieve optimal skin health through use of the proper cosmeceuticals and prescription medications. It is up to you and your staff to save your patients from falling prey to persuasive salespeople with no scientific knowledge or concern for long-term skin health.

Dr. Baumann is chief executive officer of the Baumann Cosmetic & Research Institute in the Design District in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann wrote the textbook “Cosmetic Dermatology: Principles and Practice” (New York: McGraw-Hill, 2002), and a book for consumers, “The Skin Type Solution” (New York: Bantam Dell, 2006). Her latest book, “Cosmeceuticals and Cosmetic Ingredients,” was published in November 2014. Dr. Baumann has received funding for clinical grants from Allergan, Aveeno, Avon Products, Evolus, Galderma, GlaxoSmithKline, Kythera Biopharmaceuticals, Mary Kay, Medicis Pharmaceuticals, Neutrogena, Philosophy, Topix Pharmaceuticals, and Unilever. Dr. Baumann also developed and owns the Baumann Skin Type Solution skin typing systems and related products.

The ethics behind selling skin care products to patients has been hotly debated within the field of cosmetic dermatology for several decades. In 15 years of practice, I have come to the conclusion that patients want you to and need you to because otherwise they are easily taken advantage of. Other physicians are doing it but we – the dermatologists – are the most qualified to offer skin care advice. This article will discuss the reasons that you need to get over the ethical dilemma and offer skin care to your patients.

Using the correct skin care regimen for the face and body will improve outcomes

Whether a patient suffers from acne, rosacea, melasma, psoriasis, eczema, contact dermatitis, or even tinea versicolor, using the proper skin care regimen will improve outcomes by affecting the skin barrier, pH, hydration level, and function of the keratinocytes and fibroblasts. In fact, every personal care product that touches the skin has an impact on skin health. For example, if a patient uses a detergent-laden bar soap, the skin barrier will be impaired, which can cause them to react to allergens and irritants. Personal care products can affect the skin pH; this is shown to play a role in Malassezia colonization in atopic dermatitis patients (J Clin Med. 2015;4[6]:1217-28). As dermatologists, we know better than anyone that daily use of SPF improves skin health and lowers the risk of postinflammatory pigmentation. We all agree that patients should cleanse the skin and apply a SPF every day. Giving them guidance about which to choose is very important.

Giving the patient exact instructions will lead to improved compliance

Why should recommending skin care products be perceived differently than prescribing a prescription medication? We should prescribe to our patients in writing the exact skin care regimen they should use for their face or body to ensure that they understand the directions. I have been surprised by patients who have said, “I did not know I was supposed to wash my cleanser off,” or “I wash my face with hand soap.” We can help them by educating them and giving them specific instructions. Improved education and communication results in increased compliance. When you do surgery on a wound, you probably tell them to apply a topical antibiotic ointment, but do you direct them to what cleanser to use or tell them which SPF to use on the stitched wound? Providing written instructions for all dermatologic disorders and postprocedure care is necessary to improve compliance and outcomes.

Combine cosmeceuticals, prescription medications, and medical procedures

You (unlike the cosmetic counter salesperson) have the ability to combine cosmeceuticals with prescription medications and medical procedures. In fact, selling your patients the right skin care products to use after a procedure saves them a trip to the store and ensures that they use the correct products. Of course it makes sense that patients getting toxins and fillers should use a retinoid to improve skin aging; however, many general dermatologic diseases would improve with the proper skin care. For example, do you use biologics for psoriasis? Using the proper skin care to regulate skin pH and improve the skin barrier may help prevent colonization of yeast, fungus, and bacteria. The same is true for atopic patients. Do you use liquid nitrogen? Studies show that using a retinoid before a procedure speeds healing. Skin care goes way beyond wrinkles and dark circles under the eyes, so if you are not prescribing the patient an exact regimen, you are not maximizing outcomes.

I don’t have time to talk to my patients about skin care

The missing piece is that most of us don’t have the time to spend discussing skin care. This is where using a standardized scientific methodology is crucial. I developed and use a skin typing methodology in my office and have seen improved physician/patient relationships and increased patient satisfaction resulting in a significant amount of referrals. We also have noted decreased call backs and fewer adverse events from products because the patients have a better understanding of how to properly apply the cosmeceuticals and prescription products. The best part is, it does not add any time onto the patient visit when standardized methodologies are properly adopted.

What if I still do not feel comfortable profiting from the sale of skin care products?

First you need to realize that time is money and you are saving the patient the cost in time it would have taken them to go to a store, park, and shop for the correct product. I have seen data presented from several companies that show that patients usually spend a large amount of money on skin care products after they see their dermatologist. Without guidance, they will likely buy the incorrect products. If they buy the wrong product, you save them the hassle of having to make another office visit and the aggravation of the side effects from the incorrect product. These are often of poor quality or not appropriate for their skin issues. Counterfeit products are rampant on the Internet and many new companies tout worthless products with stem cells and other nonsense. Only you can help your patients make sure that money is spent on the proper products.

Conclusion

Do you really want someone else giving your patients skin care advice? Your patients deserve to have someone with your insights, knowledge, compassion, and honesty help them achieve optimal skin health through use of the proper cosmeceuticals and prescription medications. It is up to you and your staff to save your patients from falling prey to persuasive salespeople with no scientific knowledge or concern for long-term skin health.

Dr. Baumann is chief executive officer of the Baumann Cosmetic & Research Institute in the Design District in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann wrote the textbook “Cosmetic Dermatology: Principles and Practice” (New York: McGraw-Hill, 2002), and a book for consumers, “The Skin Type Solution” (New York: Bantam Dell, 2006). Her latest book, “Cosmeceuticals and Cosmetic Ingredients,” was published in November 2014. Dr. Baumann has received funding for clinical grants from Allergan, Aveeno, Avon Products, Evolus, Galderma, GlaxoSmithKline, Kythera Biopharmaceuticals, Mary Kay, Medicis Pharmaceuticals, Neutrogena, Philosophy, Topix Pharmaceuticals, and Unilever. Dr. Baumann also developed and owns the Baumann Skin Type Solution skin typing systems and related products.

The ethics behind selling skin care products to patients has been hotly debated within the field of cosmetic dermatology for several decades. In 15 years of practice, I have come to the conclusion that patients want you to and need you to because otherwise they are easily taken advantage of. Other physicians are doing it but we – the dermatologists – are the most qualified to offer skin care advice. This article will discuss the reasons that you need to get over the ethical dilemma and offer skin care to your patients.

Using the correct skin care regimen for the face and body will improve outcomes

Whether a patient suffers from acne, rosacea, melasma, psoriasis, eczema, contact dermatitis, or even tinea versicolor, using the proper skin care regimen will improve outcomes by affecting the skin barrier, pH, hydration level, and function of the keratinocytes and fibroblasts. In fact, every personal care product that touches the skin has an impact on skin health. For example, if a patient uses a detergent-laden bar soap, the skin barrier will be impaired, which can cause them to react to allergens and irritants. Personal care products can affect the skin pH; this is shown to play a role in Malassezia colonization in atopic dermatitis patients (J Clin Med. 2015;4[6]:1217-28). As dermatologists, we know better than anyone that daily use of SPF improves skin health and lowers the risk of postinflammatory pigmentation. We all agree that patients should cleanse the skin and apply a SPF every day. Giving them guidance about which to choose is very important.

Giving the patient exact instructions will lead to improved compliance

Why should recommending skin care products be perceived differently than prescribing a prescription medication? We should prescribe to our patients in writing the exact skin care regimen they should use for their face or body to ensure that they understand the directions. I have been surprised by patients who have said, “I did not know I was supposed to wash my cleanser off,” or “I wash my face with hand soap.” We can help them by educating them and giving them specific instructions. Improved education and communication results in increased compliance. When you do surgery on a wound, you probably tell them to apply a topical antibiotic ointment, but do you direct them to what cleanser to use or tell them which SPF to use on the stitched wound? Providing written instructions for all dermatologic disorders and postprocedure care is necessary to improve compliance and outcomes.

Combine cosmeceuticals, prescription medications, and medical procedures

You (unlike the cosmetic counter salesperson) have the ability to combine cosmeceuticals with prescription medications and medical procedures. In fact, selling your patients the right skin care products to use after a procedure saves them a trip to the store and ensures that they use the correct products. Of course it makes sense that patients getting toxins and fillers should use a retinoid to improve skin aging; however, many general dermatologic diseases would improve with the proper skin care. For example, do you use biologics for psoriasis? Using the proper skin care to regulate skin pH and improve the skin barrier may help prevent colonization of yeast, fungus, and bacteria. The same is true for atopic patients. Do you use liquid nitrogen? Studies show that using a retinoid before a procedure speeds healing. Skin care goes way beyond wrinkles and dark circles under the eyes, so if you are not prescribing the patient an exact regimen, you are not maximizing outcomes.

I don’t have time to talk to my patients about skin care

The missing piece is that most of us don’t have the time to spend discussing skin care. This is where using a standardized scientific methodology is crucial. I developed and use a skin typing methodology in my office and have seen improved physician/patient relationships and increased patient satisfaction resulting in a significant amount of referrals. We also have noted decreased call backs and fewer adverse events from products because the patients have a better understanding of how to properly apply the cosmeceuticals and prescription products. The best part is, it does not add any time onto the patient visit when standardized methodologies are properly adopted.

What if I still do not feel comfortable profiting from the sale of skin care products?

First you need to realize that time is money and you are saving the patient the cost in time it would have taken them to go to a store, park, and shop for the correct product. I have seen data presented from several companies that show that patients usually spend a large amount of money on skin care products after they see their dermatologist. Without guidance, they will likely buy the incorrect products. If they buy the wrong product, you save them the hassle of having to make another office visit and the aggravation of the side effects from the incorrect product. These are often of poor quality or not appropriate for their skin issues. Counterfeit products are rampant on the Internet and many new companies tout worthless products with stem cells and other nonsense. Only you can help your patients make sure that money is spent on the proper products.

Conclusion

Do you really want someone else giving your patients skin care advice? Your patients deserve to have someone with your insights, knowledge, compassion, and honesty help them achieve optimal skin health through use of the proper cosmeceuticals and prescription medications. It is up to you and your staff to save your patients from falling prey to persuasive salespeople with no scientific knowledge or concern for long-term skin health.

Dr. Baumann is chief executive officer of the Baumann Cosmetic & Research Institute in the Design District in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann wrote the textbook “Cosmetic Dermatology: Principles and Practice” (New York: McGraw-Hill, 2002), and a book for consumers, “The Skin Type Solution” (New York: Bantam Dell, 2006). Her latest book, “Cosmeceuticals and Cosmetic Ingredients,” was published in November 2014. Dr. Baumann has received funding for clinical grants from Allergan, Aveeno, Avon Products, Evolus, Galderma, GlaxoSmithKline, Kythera Biopharmaceuticals, Mary Kay, Medicis Pharmaceuticals, Neutrogena, Philosophy, Topix Pharmaceuticals, and Unilever. Dr. Baumann also developed and owns the Baumann Skin Type Solution skin typing systems and related products.

Just as we learned early in life that 70% of the human body is composed of water, water covers approximately the same percentage of the earth’s surface. While fishing and harvesting of algae have occurred throughout human history,¹ it has only been since the 1970s that widespread scientific interest in the great biological and chemical diversity of the vast oceans of the world has led to investigations into medical and cosmetic applications of the rich life beneath the sea.² During this period, the marine environment has been found to boast multiple organisms with unique metabolisms adapted for survival in challenging conditions, yielding secondary metabolites, some of which have become valuable in the pharmaceutical and cosmeceutical markets.^3,4 Thus, the inclusion of bioactive substances from the sea in drugs and cosmetic products is primarily a recent phenomenon.¹ In fact, marine ingredients in cosmetics are thought to confer various benefits to skin health, including antioxidant, anti-acne, anti-wrinkle, and anti-tyrosinase activity.

Chemistry and biologic activity

Several marine microbial natural products have been found to display antimicrobial, antitumor, and anti-inflammatory activity.^2,5 And seaweed extracts (green, brown, and red algal compounds that include constituents such as phlorotannins, sulfated polysaccharides, and tyrosinase inhibitors) have been incorporated into cosmeceutical products, with a long history of traditional folk uses for various health – including skin – conditions.^3,6,7 Kim and Li reviewed the beneficial health effects of marine fungi-derived terpenoids in 2012, reporting that hundreds of these compounds have been discovered in the last few decades, with many exhibiting anti-inflammatory, anticancer, antimicrobial, and antioxidant activity.^8,9 Terpenoids, or isoprenoids, are a subclass of prenyllipids, which include prenylquinones, sterols, and terpenes, the largest class of natural substances.¹⁰

The terpenes are the largest group of biologically diverse marine compounds, and include the pseudopterosins, which are structurally discrete active metabolites of the Caribbean gorgonian soft coral Pseudopterogorgia elisabethae, which is native to the waters of the Caribbean Sea, Central Bahamas, Bermuda, the West Indies, and the Florida keys.^11,12 The most common gorgonian corals are diterpenes.¹³ Twenty-six derivatives of the octocoral P. elisabethae (designated PsA-PsZ), also known as the sea whip, sea fan, or sea plume, have been isolated.^11,12,14 Pseudopterosins were first isolated in 1986.^14,15

Based on the identified biologic activities, particularly anti-inflammatory capacity, of pseudopterosins, researchers have investigated their potential for treatment of various conditions including asthma, cancer, contact dermatitis, dermatoheliosis, HIV, photodamage, psoriasis, and rheumatoid arthritis.^1,11

After decades of extensive research of pseudopterosins, these tricyclic diterpene glycosides are thought to provide superior anti-inflammatory and analgesic properties, compared to standard anti-inflammatory treatments, without inducing adverse side effects; they also offer marked antimicrobial and wound-healing effects.^{3,11,14,16-19}

Other marine diterpene glycosides include eleutherobins and fucosides, which also exhibit notable biologic activity.¹⁵ In particular, the anti-inflammatory and analgesic activities of pseudopterosins have been found to be concentration- and dose-dependently more potent than the standard-bearing indomethacin.^11,14,17

Marine ingredients in topical formulations

The first product to include pseudopterosins was the skin formulation Resilience marketed by Estée Lauder over a decade ago.^19,20 Natural marine ingredients have since been incorporated into a few more products, such as Imedeen, an oral skin care preparation that contains Marine Complex.²¹

In 2012, Rietveld et al. ascertained whether the Marine Complex from Imedeen could variously alter skin morphogenesis in female and male human skin equivalents. Cells were culled from female and male donors between the ages of 30 and 45 years for human skin equivalents that were cultured for 7 or 11 weeks with or without Marine Complex. The investigators found that the number of Ki67-positive epidermal cells was greatly augmented by Marine Complex in female human skin equivalents. The Marine Complex significantly spurred the level of secreted pro-collagen I and elevated the deposition of laminin 332 and collagen type VII in the dermis. Human skin equivalents treated with Marine Complex also exhibited more viable epidermal cell layers and a thicker dermal extracellular matrix, compared to controls, with these effects less salient in male human skin equivalents. The investigators concluded that supplementation with Marine Complex positively stimulated overall human skin equivalent tissue formation, with its effects on the basement membrane and dermal constituents suggestive of potential for use against human skin aging.²¹

Previously, Xhauflaire-Uhoda et al. evaluated the skin hydrating and firming dose-response effects of cosmetic preparations enriched in algae- and fish collagen–derived substances in randomized controlled double-blind medium-term (12 subjects aged 18-55 years) and short-term (3 subjects over the age of 50) trials. In the short term, serum formulations enriched in marine compounds manifested a superior moisturizing effect on the forearm compared with creams. In later stages, cream formulations were more active, especially after repeated applications. Investigators observed a sustained firming activity in association with both the lotion and cream during treatment, but such results did not persist after treatment was stopped.²²

Product development

Technological advances, including sampling strategies, nanoscale nuclear magnetic resonance for structure determination, total chemical synthesis, fermentation, exploration of genomic and metagenomic resources, combinatorial biosynthesis, synthetic biology, and biotechnology represent important ways in which novel marine natural products are being developed, according to several authors.^1,2,4

Conclusion

Marine ingredients are a relatively new and fascinating category of substances that can and are being harnessed for pharmaceutical, cosmeceutical, cosmetic, and nutritional uses. Beyond the challenges of obtaining sufficient raw materials and producing effective formulations, the continued viability of such resources may be threatened by human exploitation of the seas and climate change. That said, the oceans offer the greatest biodiversity on the planet and dermatologic preparations derived from such sources present intriguing possibilities, particularly the apparent anti-inflammatory activity of gorgonian and other terpenes. These compounds appear to have the potential to replace, or serve as desirable alternatives to, conventional therapies for inflammatory skin disorders.

References

1. Biotechnol Adv. 2011;29(5):468-82.

2. Mar Drugs. 2013;11(3):700-17.

3. Mar Drugs. 2014;12(2):1066-101.

4. Future Med Chem. 2011;3(12):1475-89.

5. Org Lett. 2000;2(4):507-10.

6. Mar Drugs. 2013;11(1):146-64.

7. J Cosmet Dermatol. 2014;13(1):56-67.

8. Adv Food Nutr Res. 2012;65:409-13.

9. Crit Rev Microbiol. 2011;37(3):245-9.

10. Nat Chem Biol. 2007;3(7):408-14.

11. J Drugs Dermatol. 2013;12(10):1177-9.

12. J Ind Microbiol Biotechnol. 2006;33(7):532-8.

13. Nat Prod Rep. 2009;26(5):681-710.

14. Proc Natl Acad Sci USA. 1986;83(17):6238-40.

15. Bioorg Med Chem. 2011;19(22):6702-19.

16. Arch Biochem Biophys. 2004;424(1):97-104.

17. Asia Pac J Clin Nutr. 2006;15(2):143-52.

18. J Nat Prod. 2004;67(10):1672-80.

19. Mar Drugs. 2004 May;2:73-82.

20. J Nat Prod. 2004;67(8):1216-38.

21. J Cosmet Dermatol. 2012;11(3):213-22.

22. Int J Cosmet Sci. 2008;30(2):131-8.

Dr. Baumann is chief executive officer of the Baumann Cosmetic & Research Institute in the Design District in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann wrote the textbook, “Cosmetic Dermatology: Principles and Practice” (New York: McGraw-Hill, 2002), and a book for consumers, “The Skin Type Solution” (New York: Bantam Dell, 2006). She has contributed to the Cosmeceutical Critique column in Dermatology News since January 2001. Her latest book, “Cosmeceuticals and Cosmetic Ingredients,” was published in November 2014. Dr. Baumann has received funding for clinical grants from Allergan, Aveeno, Avon Products, Evolus, Galderma, GlaxoSmithKline, Kythera Biopharmaceuticals, Mary Kay, Medicis Pharmaceuticals, Neutrogena, Philosophy, Topix Pharmaceuticals, and Unilever.

Just as we learned early in life that 70% of the human body is composed of water, water covers approximately the same percentage of the earth’s surface. While fishing and harvesting of algae have occurred throughout human history,¹ it has only been since the 1970s that widespread scientific interest in the great biological and chemical diversity of the vast oceans of the world has led to investigations into medical and cosmetic applications of the rich life beneath the sea.² During this period, the marine environment has been found to boast multiple organisms with unique metabolisms adapted for survival in challenging conditions, yielding secondary metabolites, some of which have become valuable in the pharmaceutical and cosmeceutical markets.^3,4 Thus, the inclusion of bioactive substances from the sea in drugs and cosmetic products is primarily a recent phenomenon.¹ In fact, marine ingredients in cosmetics are thought to confer various benefits to skin health, including antioxidant, anti-acne, anti-wrinkle, and anti-tyrosinase activity.

Chemistry and biologic activity

Several marine microbial natural products have been found to display antimicrobial, antitumor, and anti-inflammatory activity.^2,5 And seaweed extracts (green, brown, and red algal compounds that include constituents such as phlorotannins, sulfated polysaccharides, and tyrosinase inhibitors) have been incorporated into cosmeceutical products, with a long history of traditional folk uses for various health – including skin – conditions.^3,6,7 Kim and Li reviewed the beneficial health effects of marine fungi-derived terpenoids in 2012, reporting that hundreds of these compounds have been discovered in the last few decades, with many exhibiting anti-inflammatory, anticancer, antimicrobial, and antioxidant activity.^8,9 Terpenoids, or isoprenoids, are a subclass of prenyllipids, which include prenylquinones, sterols, and terpenes, the largest class of natural substances.¹⁰

The terpenes are the largest group of biologically diverse marine compounds, and include the pseudopterosins, which are structurally discrete active metabolites of the Caribbean gorgonian soft coral Pseudopterogorgia elisabethae, which is native to the waters of the Caribbean Sea, Central Bahamas, Bermuda, the West Indies, and the Florida keys.^11,12 The most common gorgonian corals are diterpenes.¹³ Twenty-six derivatives of the octocoral P. elisabethae (designated PsA-PsZ), also known as the sea whip, sea fan, or sea plume, have been isolated.^11,12,14 Pseudopterosins were first isolated in 1986.^14,15

Based on the identified biologic activities, particularly anti-inflammatory capacity, of pseudopterosins, researchers have investigated their potential for treatment of various conditions including asthma, cancer, contact dermatitis, dermatoheliosis, HIV, photodamage, psoriasis, and rheumatoid arthritis.^1,11

After decades of extensive research of pseudopterosins, these tricyclic diterpene glycosides are thought to provide superior anti-inflammatory and analgesic properties, compared to standard anti-inflammatory treatments, without inducing adverse side effects; they also offer marked antimicrobial and wound-healing effects.^{3,11,14,16-19}

Other marine diterpene glycosides include eleutherobins and fucosides, which also exhibit notable biologic activity.¹⁵ In particular, the anti-inflammatory and analgesic activities of pseudopterosins have been found to be concentration- and dose-dependently more potent than the standard-bearing indomethacin.^11,14,17

Marine ingredients in topical formulations

The first product to include pseudopterosins was the skin formulation Resilience marketed by Estée Lauder over a decade ago.^19,20 Natural marine ingredients have since been incorporated into a few more products, such as Imedeen, an oral skin care preparation that contains Marine Complex.²¹

In 2012, Rietveld et al. ascertained whether the Marine Complex from Imedeen could variously alter skin morphogenesis in female and male human skin equivalents. Cells were culled from female and male donors between the ages of 30 and 45 years for human skin equivalents that were cultured for 7 or 11 weeks with or without Marine Complex. The investigators found that the number of Ki67-positive epidermal cells was greatly augmented by Marine Complex in female human skin equivalents. The Marine Complex significantly spurred the level of secreted pro-collagen I and elevated the deposition of laminin 332 and collagen type VII in the dermis. Human skin equivalents treated with Marine Complex also exhibited more viable epidermal cell layers and a thicker dermal extracellular matrix, compared to controls, with these effects less salient in male human skin equivalents. The investigators concluded that supplementation with Marine Complex positively stimulated overall human skin equivalent tissue formation, with its effects on the basement membrane and dermal constituents suggestive of potential for use against human skin aging.²¹

Previously, Xhauflaire-Uhoda et al. evaluated the skin hydrating and firming dose-response effects of cosmetic preparations enriched in algae- and fish collagen–derived substances in randomized controlled double-blind medium-term (12 subjects aged 18-55 years) and short-term (3 subjects over the age of 50) trials. In the short term, serum formulations enriched in marine compounds manifested a superior moisturizing effect on the forearm compared with creams. In later stages, cream formulations were more active, especially after repeated applications. Investigators observed a sustained firming activity in association with both the lotion and cream during treatment, but such results did not persist after treatment was stopped.²²

Product development

Technological advances, including sampling strategies, nanoscale nuclear magnetic resonance for structure determination, total chemical synthesis, fermentation, exploration of genomic and metagenomic resources, combinatorial biosynthesis, synthetic biology, and biotechnology represent important ways in which novel marine natural products are being developed, according to several authors.^1,2,4

Conclusion

Marine ingredients are a relatively new and fascinating category of substances that can and are being harnessed for pharmaceutical, cosmeceutical, cosmetic, and nutritional uses. Beyond the challenges of obtaining sufficient raw materials and producing effective formulations, the continued viability of such resources may be threatened by human exploitation of the seas and climate change. That said, the oceans offer the greatest biodiversity on the planet and dermatologic preparations derived from such sources present intriguing possibilities, particularly the apparent anti-inflammatory activity of gorgonian and other terpenes. These compounds appear to have the potential to replace, or serve as desirable alternatives to, conventional therapies for inflammatory skin disorders.

References

1. Biotechnol Adv. 2011;29(5):468-82.

2. Mar Drugs. 2013;11(3):700-17.

3. Mar Drugs. 2014;12(2):1066-101.

4. Future Med Chem. 2011;3(12):1475-89.

5. Org Lett. 2000;2(4):507-10.

6. Mar Drugs. 2013;11(1):146-64.

7. J Cosmet Dermatol. 2014;13(1):56-67.

8. Adv Food Nutr Res. 2012;65:409-13.

9. Crit Rev Microbiol. 2011;37(3):245-9.

10. Nat Chem Biol. 2007;3(7):408-14.

11. J Drugs Dermatol. 2013;12(10):1177-9.

12. J Ind Microbiol Biotechnol. 2006;33(7):532-8.

13. Nat Prod Rep. 2009;26(5):681-710.

14. Proc Natl Acad Sci USA. 1986;83(17):6238-40.

15. Bioorg Med Chem. 2011;19(22):6702-19.

16. Arch Biochem Biophys. 2004;424(1):97-104.

17. Asia Pac J Clin Nutr. 2006;15(2):143-52.

18. J Nat Prod. 2004;67(10):1672-80.

19. Mar Drugs. 2004 May;2:73-82.

20. J Nat Prod. 2004;67(8):1216-38.

21. J Cosmet Dermatol. 2012;11(3):213-22.

22. Int J Cosmet Sci. 2008;30(2):131-8.

Dr. Baumann is chief executive officer of the Baumann Cosmetic & Research Institute in the Design District in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann wrote the textbook, “Cosmetic Dermatology: Principles and Practice” (New York: McGraw-Hill, 2002), and a book for consumers, “The Skin Type Solution” (New York: Bantam Dell, 2006). She has contributed to the Cosmeceutical Critique column in Dermatology News since January 2001. Her latest book, “Cosmeceuticals and Cosmetic Ingredients,” was published in November 2014. Dr. Baumann has received funding for clinical grants from Allergan, Aveeno, Avon Products, Evolus, Galderma, GlaxoSmithKline, Kythera Biopharmaceuticals, Mary Kay, Medicis Pharmaceuticals, Neutrogena, Philosophy, Topix Pharmaceuticals, and Unilever.

Just as we learned early in life that 70% of the human body is composed of water, water covers approximately the same percentage of the earth’s surface. While fishing and harvesting of algae have occurred throughout human history,¹ it has only been since the 1970s that widespread scientific interest in the great biological and chemical diversity of the vast oceans of the world has led to investigations into medical and cosmetic applications of the rich life beneath the sea.² During this period, the marine environment has been found to boast multiple organisms with unique metabolisms adapted for survival in challenging conditions, yielding secondary metabolites, some of which have become valuable in the pharmaceutical and cosmeceutical markets.^3,4 Thus, the inclusion of bioactive substances from the sea in drugs and cosmetic products is primarily a recent phenomenon.¹ In fact, marine ingredients in cosmetics are thought to confer various benefits to skin health, including antioxidant, anti-acne, anti-wrinkle, and anti-tyrosinase activity.

Chemistry and biologic activity

Several marine microbial natural products have been found to display antimicrobial, antitumor, and anti-inflammatory activity.^2,5 And seaweed extracts (green, brown, and red algal compounds that include constituents such as phlorotannins, sulfated polysaccharides, and tyrosinase inhibitors) have been incorporated into cosmeceutical products, with a long history of traditional folk uses for various health – including skin – conditions.^3,6,7 Kim and Li reviewed the beneficial health effects of marine fungi-derived terpenoids in 2012, reporting that hundreds of these compounds have been discovered in the last few decades, with many exhibiting anti-inflammatory, anticancer, antimicrobial, and antioxidant activity.^8,9 Terpenoids, or isoprenoids, are a subclass of prenyllipids, which include prenylquinones, sterols, and terpenes, the largest class of natural substances.¹⁰

The terpenes are the largest group of biologically diverse marine compounds, and include the pseudopterosins, which are structurally discrete active metabolites of the Caribbean gorgonian soft coral Pseudopterogorgia elisabethae, which is native to the waters of the Caribbean Sea, Central Bahamas, Bermuda, the West Indies, and the Florida keys.^11,12 The most common gorgonian corals are diterpenes.¹³ Twenty-six derivatives of the octocoral P. elisabethae (designated PsA-PsZ), also known as the sea whip, sea fan, or sea plume, have been isolated.^11,12,14 Pseudopterosins were first isolated in 1986.^14,15

Based on the identified biologic activities, particularly anti-inflammatory capacity, of pseudopterosins, researchers have investigated their potential for treatment of various conditions including asthma, cancer, contact dermatitis, dermatoheliosis, HIV, photodamage, psoriasis, and rheumatoid arthritis.^1,11

After decades of extensive research of pseudopterosins, these tricyclic diterpene glycosides are thought to provide superior anti-inflammatory and analgesic properties, compared to standard anti-inflammatory treatments, without inducing adverse side effects; they also offer marked antimicrobial and wound-healing effects.^{3,11,14,16-19}

Other marine diterpene glycosides include eleutherobins and fucosides, which also exhibit notable biologic activity.¹⁵ In particular, the anti-inflammatory and analgesic activities of pseudopterosins have been found to be concentration- and dose-dependently more potent than the standard-bearing indomethacin.^11,14,17

Marine ingredients in topical formulations

The first product to include pseudopterosins was the skin formulation Resilience marketed by Estée Lauder over a decade ago.^19,20 Natural marine ingredients have since been incorporated into a few more products, such as Imedeen, an oral skin care preparation that contains Marine Complex.²¹

In 2012, Rietveld et al. ascertained whether the Marine Complex from Imedeen could variously alter skin morphogenesis in female and male human skin equivalents. Cells were culled from female and male donors between the ages of 30 and 45 years for human skin equivalents that were cultured for 7 or 11 weeks with or without Marine Complex. The investigators found that the number of Ki67-positive epidermal cells was greatly augmented by Marine Complex in female human skin equivalents. The Marine Complex significantly spurred the level of secreted pro-collagen I and elevated the deposition of laminin 332 and collagen type VII in the dermis. Human skin equivalents treated with Marine Complex also exhibited more viable epidermal cell layers and a thicker dermal extracellular matrix, compared to controls, with these effects less salient in male human skin equivalents. The investigators concluded that supplementation with Marine Complex positively stimulated overall human skin equivalent tissue formation, with its effects on the basement membrane and dermal constituents suggestive of potential for use against human skin aging.²¹

Previously, Xhauflaire-Uhoda et al. evaluated the skin hydrating and firming dose-response effects of cosmetic preparations enriched in algae- and fish collagen–derived substances in randomized controlled double-blind medium-term (12 subjects aged 18-55 years) and short-term (3 subjects over the age of 50) trials. In the short term, serum formulations enriched in marine compounds manifested a superior moisturizing effect on the forearm compared with creams. In later stages, cream formulations were more active, especially after repeated applications. Investigators observed a sustained firming activity in association with both the lotion and cream during treatment, but such results did not persist after treatment was stopped.²²

Product development

Technological advances, including sampling strategies, nanoscale nuclear magnetic resonance for structure determination, total chemical synthesis, fermentation, exploration of genomic and metagenomic resources, combinatorial biosynthesis, synthetic biology, and biotechnology represent important ways in which novel marine natural products are being developed, according to several authors.^1,2,4

Conclusion

Marine ingredients are a relatively new and fascinating category of substances that can and are being harnessed for pharmaceutical, cosmeceutical, cosmetic, and nutritional uses. Beyond the challenges of obtaining sufficient raw materials and producing effective formulations, the continued viability of such resources may be threatened by human exploitation of the seas and climate change. That said, the oceans offer the greatest biodiversity on the planet and dermatologic preparations derived from such sources present intriguing possibilities, particularly the apparent anti-inflammatory activity of gorgonian and other terpenes. These compounds appear to have the potential to replace, or serve as desirable alternatives to, conventional therapies for inflammatory skin disorders.

References

1. Biotechnol Adv. 2011;29(5):468-82.

2. Mar Drugs. 2013;11(3):700-17.

3. Mar Drugs. 2014;12(2):1066-101.

4. Future Med Chem. 2011;3(12):1475-89.

5. Org Lett. 2000;2(4):507-10.

6. Mar Drugs. 2013;11(1):146-64.

7. J Cosmet Dermatol. 2014;13(1):56-67.

8. Adv Food Nutr Res. 2012;65:409-13.

9. Crit Rev Microbiol. 2011;37(3):245-9.

10. Nat Chem Biol. 2007;3(7):408-14.

11. J Drugs Dermatol. 2013;12(10):1177-9.

12. J Ind Microbiol Biotechnol. 2006;33(7):532-8.

13. Nat Prod Rep. 2009;26(5):681-710.

14. Proc Natl Acad Sci USA. 1986;83(17):6238-40.

15. Bioorg Med Chem. 2011;19(22):6702-19.

16. Arch Biochem Biophys. 2004;424(1):97-104.

17. Asia Pac J Clin Nutr. 2006;15(2):143-52.

18. J Nat Prod. 2004;67(10):1672-80.

19. Mar Drugs. 2004 May;2:73-82.

20. J Nat Prod. 2004;67(8):1216-38.

21. J Cosmet Dermatol. 2012;11(3):213-22.

22. Int J Cosmet Sci. 2008;30(2):131-8.

Dr. Baumann is chief executive officer of the Baumann Cosmetic & Research Institute in the Design District in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann wrote the textbook, “Cosmetic Dermatology: Principles and Practice” (New York: McGraw-Hill, 2002), and a book for consumers, “The Skin Type Solution” (New York: Bantam Dell, 2006). She has contributed to the Cosmeceutical Critique column in Dermatology News since January 2001. Her latest book, “Cosmeceuticals and Cosmetic Ingredients,” was published in November 2014. Dr. Baumann has received funding for clinical grants from Allergan, Aveeno, Avon Products, Evolus, Galderma, GlaxoSmithKline, Kythera Biopharmaceuticals, Mary Kay, Medicis Pharmaceuticals, Neutrogena, Philosophy, Topix Pharmaceuticals, and Unilever.

Known as sweet chestnut, Castanea sativa is a member of the Fagaceae family, and is found in abundance in Southern and Southeastern Europe and Asia.¹ In traditional medicine, chestnut tree flower preparations have been used for various indications.² Chestnut has been used in French folk medicine as a tea to treat severe cough, colds, and bronchitis as well as diarrhea.^2-6 In modern times, C. sativa leaf extract has been described as having the capacity to scavenge various free radicals associated with oxidative stress induced by ultraviolet exposure.⁷

Traditional uses

A 2014 study of the therapeutic and traditional uses of the plants native to the Western Italian Alps revealed that C. sativa has long been important in the region, typically for food and wood.⁸ But medical uses have been uncovered in that region as well. In fact, ancient Romans found C. sativa to exhibit antibacterial, astringent, antitoxic, and tonic qualities, with chestnut honey used then to dress chronic wounds, burns, and skin ulcers.⁹ A 2014 study by Carocho et al. of the phytochemical profile and antioxidant activity of C. sativa flowers is noteworthy for buttressing the reported health benefits of the use of chestnut flower infusions and decoctions in traditional medicine.²

Antioxidant activity

In 2005, Calliste et al. investigated the antioxidant potential of C. sativa leaf to act against the stable free radical 2,2-diphenyl-1-pycrylhydrazyl, superoxide anion, and hydroxyl radical. Using electronic spin resonance, the investigators showed that C. sativa exhibited high antioxidant potential equivalent to reference antioxidants quercetin and vitamin E.³

Three years later, Almeida et al. conducted an in vitro assessment of an ethanol/water (7:3) extract from C. sativa leaves and an ethanol/water (2:3) extract from Quercus robur (English oak) leaves, finding that both plants demonstrated a high potency to scavenge various reactive oxygen and nitrogen species. The researchers concluded that these findings supported the burgeoning interest in these extracts for use in topical antioxidant formulations.⁴ An in vivo investigation using an ethanol/water (7:3) extract from C. sativa conducted by the same team later in the year yielded similar results, with the researchers concluding that chestnut extract has the potential to confer benefits against photoaging and other oxidative stress–mediated conditions when included in an appropriately formulated topical antioxidant preparation.⁶ Subsequently, Barreira et al. demonstrated that chestnut skin and leaves exhibited sufficient antioxidant potency to warrant use in novel antioxidant formulations.¹⁰

In 2015, Almeida et al. characterized an antioxidant semisolid surfactant-free topical formulation featuring C. sativa leaf extract. In the process of ascertaining the physical, functional, and microbiologic stability of the antioxidant formulation, the investigators identified a hydrating effect and good skin tolerance, which they concluded suggested a capacity to prevent or treat cutaneous conditions in which oxidative stress plays a role.¹¹

Photoprotective potential

In 2010, Sapkota et al. evaluated the antioxidant and antimelanogenic characteristics of several prebloom and full-bloom chestnut flower extracts, finding that a prebloom methanol extract and an ethanol extract evinced the greatest levels of phenolic and flavonoid compounds. These extracts also displayed the best radical scavenging and mushroom tyrosinase–inhibiting activities. Notably, the prebloom extract was effective in protecting the skin from the deleterious impact of UV radiation. The investigators also observed that all of the tested extracts lowered the tyrosinase activity and melanin formation of SK-MEL-2 cells similarly to arbutin. They ascribed the antimelanogenic effects of chestnut flower extracts to their antioxidant-mediated inhibitory effects on tyrosinase. They concluded that chestnut flower extracts have considerable potential as cosmetic agents.¹²

By Wildfeuer/ Wikimedia Commons/ CC BY-SA 3.0

Recently, Almeida et al. studied the protective effects in a human keratinocyte cell line of C. sativa extract at various concentrations (0.001-, 0.01-, 0.05-, and 0.1-mcg/mL) against UV-induced DNA damage. They found that the chestnut extract concentration dependently protected against UV-mediated DNA damage, with the 0.1-mcg/mL concentration affording maximum protection (66.4%). This result was considered to be a direct antioxidant effect attributed to various phenolic antioxidants present in C. sativa. In addition, the investigators observed no phototoxic or genotoxic effects on HaCaT cells incubated with up to 0.1 mcg/mL of chestnut leaf extract. They concluded that C. sativa leaf extract has the potential to prevent or mitigate UV-induced harm to the skin.⁷

Other benefits and bioactivity

Assessments of C. sativa by-products have shown a favorable profile of bioactive constituents that demonstrate antioxidant, anticarcinogenic, and cardioprotective activity. Braga et al. conducted a 2015 review that concluded these compounds, as part of agro-industrial waste, offer value to the pharmaceutical, cosmetics, and food industries, with the potential to lower pollution costs and raise profits while enhancing social, economic, and environmental sustainability in growing regions.¹

A related chestnut species also has been linked to dermatologic uses. In East Asia, a skin firming/antiwrinkle formulation features the inner shell of Castanea crenata as an active ingredient.¹³ In 2002, Chi et al. showed that the chestnut inner shell extract improved cell-associated expression of the adhesion molecules fibronectin and vitronectin. They also found that scoparone (6,7-dimethoxycoumarin) isolated from the chestnut extract exhibited comparable qualities. The investigators concluded that the enhanced expression of adhesion molecules imparted by the chestnut inner shell extract may account for the prevention of cell detachment and the manifestation of antiaging effects.¹³

Allergy

It is worth noting that chestnut is one of the many allergens associated with the latex-fruit syndrome.¹⁴ However, in a patch test investigation of the skin irritation potential of C. sativa leaf extract in 20 volunteers, Almeida et al. identified five phenolic compounds in the extract (chlorogenic acid, ellagic acid, rutin, isoquercitrin, and hyperoside) and found it safe for topical application.⁶ Chestnut is considered to pose a low to moderate risk of inducing allergic reactions.⁹

Conclusion

Recent research appears to suggest the in vitro antioxidant activity of sweet chestnut and potential for use in topical formulations. There remains a paucity of in vivo evidence, however. While much more research is necessary to determine whether it has a place in the dermatologic armamentarium, current data are intriguing.

References

1. Nat Prod Res. 2015;29(1):1-18

2. Biomed Res Int. 2014;2014:232956

3. J Agric Food Chem. 2005 Jan 26;53(2):282-8

4. J Photochem Photobiol B. 2008 May 29;91(2-3):87-95

5. A Modern Herbal (vol. I). New York: Dover Publications, 1971, p. 195

6. Basic Clin Pharmacol Toxicol. 2008 Nov;103(5):461-7

7. J Photochem Photobiol B. 2015 Mar;144C:28-34

8. J Ethnopharmacol. 2014 Aug 8;155(1):463-84

9. J Sci Food Agric. 2010 Aug 15;90(10):1578-89

10. Food Sci Technol Int. 2010 June;16(3):209-16

11. Drug Dev Ind Pharm. 2015 Jan;41(1):148-55

12. Biosci Biotechnol Biochem. 2010;74(8):1527-33

13. Arch Pharm Res. 2002 Aug;25(4):469-74

14. Allergy. 2007 Nov;62(11):1277-81

Dr. Baumann is chief executive officer of the Baumann Cosmetic & Research Institute in the Design District in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann wrote the textbook “Cosmetic Dermatology: Principles and Practice” (New York: McGraw-Hill, 2002), and a book for consumers, “The Skin Type Solution” (New York: Bantam Dell, 2006). Her latest book, “Cosmeceuticals and Cosmetic Ingredients,” was published in November 2014. Dr. Baumann has received funding for clinical grants from Allergan, Aveeno, Avon Products, Evolus, Galderma, GlaxoSmithKline, Kythera Biopharmaceuticals, Mary Kay, Medicis Pharmaceuticals, Neutrogena, Philosophy, Topix Pharmaceuticals, and Unilever.

Known as sweet chestnut, Castanea sativa is a member of the Fagaceae family, and is found in abundance in Southern and Southeastern Europe and Asia.¹ In traditional medicine, chestnut tree flower preparations have been used for various indications.² Chestnut has been used in French folk medicine as a tea to treat severe cough, colds, and bronchitis as well as diarrhea.^2-6 In modern times, C. sativa leaf extract has been described as having the capacity to scavenge various free radicals associated with oxidative stress induced by ultraviolet exposure.⁷

Traditional uses

A 2014 study of the therapeutic and traditional uses of the plants native to the Western Italian Alps revealed that C. sativa has long been important in the region, typically for food and wood.⁸ But medical uses have been uncovered in that region as well. In fact, ancient Romans found C. sativa to exhibit antibacterial, astringent, antitoxic, and tonic qualities, with chestnut honey used then to dress chronic wounds, burns, and skin ulcers.⁹ A 2014 study by Carocho et al. of the phytochemical profile and antioxidant activity of C. sativa flowers is noteworthy for buttressing the reported health benefits of the use of chestnut flower infusions and decoctions in traditional medicine.²

Antioxidant activity

In 2005, Calliste et al. investigated the antioxidant potential of C. sativa leaf to act against the stable free radical 2,2-diphenyl-1-pycrylhydrazyl, superoxide anion, and hydroxyl radical. Using electronic spin resonance, the investigators showed that C. sativa exhibited high antioxidant potential equivalent to reference antioxidants quercetin and vitamin E.³

Three years later, Almeida et al. conducted an in vitro assessment of an ethanol/water (7:3) extract from C. sativa leaves and an ethanol/water (2:3) extract from Quercus robur (English oak) leaves, finding that both plants demonstrated a high potency to scavenge various reactive oxygen and nitrogen species. The researchers concluded that these findings supported the burgeoning interest in these extracts for use in topical antioxidant formulations.⁴ An in vivo investigation using an ethanol/water (7:3) extract from C. sativa conducted by the same team later in the year yielded similar results, with the researchers concluding that chestnut extract has the potential to confer benefits against photoaging and other oxidative stress–mediated conditions when included in an appropriately formulated topical antioxidant preparation.⁶ Subsequently, Barreira et al. demonstrated that chestnut skin and leaves exhibited sufficient antioxidant potency to warrant use in novel antioxidant formulations.¹⁰

In 2015, Almeida et al. characterized an antioxidant semisolid surfactant-free topical formulation featuring C. sativa leaf extract. In the process of ascertaining the physical, functional, and microbiologic stability of the antioxidant formulation, the investigators identified a hydrating effect and good skin tolerance, which they concluded suggested a capacity to prevent or treat cutaneous conditions in which oxidative stress plays a role.¹¹

Photoprotective potential

In 2010, Sapkota et al. evaluated the antioxidant and antimelanogenic characteristics of several prebloom and full-bloom chestnut flower extracts, finding that a prebloom methanol extract and an ethanol extract evinced the greatest levels of phenolic and flavonoid compounds. These extracts also displayed the best radical scavenging and mushroom tyrosinase–inhibiting activities. Notably, the prebloom extract was effective in protecting the skin from the deleterious impact of UV radiation. The investigators also observed that all of the tested extracts lowered the tyrosinase activity and melanin formation of SK-MEL-2 cells similarly to arbutin. They ascribed the antimelanogenic effects of chestnut flower extracts to their antioxidant-mediated inhibitory effects on tyrosinase. They concluded that chestnut flower extracts have considerable potential as cosmetic agents.¹²

By Wildfeuer/ Wikimedia Commons/ CC BY-SA 3.0

Recently, Almeida et al. studied the protective effects in a human keratinocyte cell line of C. sativa extract at various concentrations (0.001-, 0.01-, 0.05-, and 0.1-mcg/mL) against UV-induced DNA damage. They found that the chestnut extract concentration dependently protected against UV-mediated DNA damage, with the 0.1-mcg/mL concentration affording maximum protection (66.4%). This result was considered to be a direct antioxidant effect attributed to various phenolic antioxidants present in C. sativa. In addition, the investigators observed no phototoxic or genotoxic effects on HaCaT cells incubated with up to 0.1 mcg/mL of chestnut leaf extract. They concluded that C. sativa leaf extract has the potential to prevent or mitigate UV-induced harm to the skin.⁷

Other benefits and bioactivity

Assessments of C. sativa by-products have shown a favorable profile of bioactive constituents that demonstrate antioxidant, anticarcinogenic, and cardioprotective activity. Braga et al. conducted a 2015 review that concluded these compounds, as part of agro-industrial waste, offer value to the pharmaceutical, cosmetics, and food industries, with the potential to lower pollution costs and raise profits while enhancing social, economic, and environmental sustainability in growing regions.¹

A related chestnut species also has been linked to dermatologic uses. In East Asia, a skin firming/antiwrinkle formulation features the inner shell of Castanea crenata as an active ingredient.¹³ In 2002, Chi et al. showed that the chestnut inner shell extract improved cell-associated expression of the adhesion molecules fibronectin and vitronectin. They also found that scoparone (6,7-dimethoxycoumarin) isolated from the chestnut extract exhibited comparable qualities. The investigators concluded that the enhanced expression of adhesion molecules imparted by the chestnut inner shell extract may account for the prevention of cell detachment and the manifestation of antiaging effects.¹³

Allergy

It is worth noting that chestnut is one of the many allergens associated with the latex-fruit syndrome.¹⁴ However, in a patch test investigation of the skin irritation potential of C. sativa leaf extract in 20 volunteers, Almeida et al. identified five phenolic compounds in the extract (chlorogenic acid, ellagic acid, rutin, isoquercitrin, and hyperoside) and found it safe for topical application.⁶ Chestnut is considered to pose a low to moderate risk of inducing allergic reactions.⁹

Conclusion

Recent research appears to suggest the in vitro antioxidant activity of sweet chestnut and potential for use in topical formulations. There remains a paucity of in vivo evidence, however. While much more research is necessary to determine whether it has a place in the dermatologic armamentarium, current data are intriguing.

References

1. Nat Prod Res. 2015;29(1):1-18

2. Biomed Res Int. 2014;2014:232956

3. J Agric Food Chem. 2005 Jan 26;53(2):282-8

4. J Photochem Photobiol B. 2008 May 29;91(2-3):87-95

5. A Modern Herbal (vol. I). New York: Dover Publications, 1971, p. 195

6. Basic Clin Pharmacol Toxicol. 2008 Nov;103(5):461-7

7. J Photochem Photobiol B. 2015 Mar;144C:28-34

8. J Ethnopharmacol. 2014 Aug 8;155(1):463-84

9. J Sci Food Agric. 2010 Aug 15;90(10):1578-89

10. Food Sci Technol Int. 2010 June;16(3):209-16

11. Drug Dev Ind Pharm. 2015 Jan;41(1):148-55

12. Biosci Biotechnol Biochem. 2010;74(8):1527-33

13. Arch Pharm Res. 2002 Aug;25(4):469-74

14. Allergy. 2007 Nov;62(11):1277-81

Dr. Baumann is chief executive officer of the Baumann Cosmetic & Research Institute in the Design District in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann wrote the textbook “Cosmetic Dermatology: Principles and Practice” (New York: McGraw-Hill, 2002), and a book for consumers, “The Skin Type Solution” (New York: Bantam Dell, 2006). Her latest book, “Cosmeceuticals and Cosmetic Ingredients,” was published in November 2014. Dr. Baumann has received funding for clinical grants from Allergan, Aveeno, Avon Products, Evolus, Galderma, GlaxoSmithKline, Kythera Biopharmaceuticals, Mary Kay, Medicis Pharmaceuticals, Neutrogena, Philosophy, Topix Pharmaceuticals, and Unilever.

Known as sweet chestnut, Castanea sativa is a member of the Fagaceae family, and is found in abundance in Southern and Southeastern Europe and Asia.¹ In traditional medicine, chestnut tree flower preparations have been used for various indications.² Chestnut has been used in French folk medicine as a tea to treat severe cough, colds, and bronchitis as well as diarrhea.^2-6 In modern times, C. sativa leaf extract has been described as having the capacity to scavenge various free radicals associated with oxidative stress induced by ultraviolet exposure.⁷

Traditional uses

A 2014 study of the therapeutic and traditional uses of the plants native to the Western Italian Alps revealed that C. sativa has long been important in the region, typically for food and wood.⁸ But medical uses have been uncovered in that region as well. In fact, ancient Romans found C. sativa to exhibit antibacterial, astringent, antitoxic, and tonic qualities, with chestnut honey used then to dress chronic wounds, burns, and skin ulcers.⁹ A 2014 study by Carocho et al. of the phytochemical profile and antioxidant activity of C. sativa flowers is noteworthy for buttressing the reported health benefits of the use of chestnut flower infusions and decoctions in traditional medicine.²

Antioxidant activity

In 2005, Calliste et al. investigated the antioxidant potential of C. sativa leaf to act against the stable free radical 2,2-diphenyl-1-pycrylhydrazyl, superoxide anion, and hydroxyl radical. Using electronic spin resonance, the investigators showed that C. sativa exhibited high antioxidant potential equivalent to reference antioxidants quercetin and vitamin E.³

Three years later, Almeida et al. conducted an in vitro assessment of an ethanol/water (7:3) extract from C. sativa leaves and an ethanol/water (2:3) extract from Quercus robur (English oak) leaves, finding that both plants demonstrated a high potency to scavenge various reactive oxygen and nitrogen species. The researchers concluded that these findings supported the burgeoning interest in these extracts for use in topical antioxidant formulations.⁴ An in vivo investigation using an ethanol/water (7:3) extract from C. sativa conducted by the same team later in the year yielded similar results, with the researchers concluding that chestnut extract has the potential to confer benefits against photoaging and other oxidative stress–mediated conditions when included in an appropriately formulated topical antioxidant preparation.⁶ Subsequently, Barreira et al. demonstrated that chestnut skin and leaves exhibited sufficient antioxidant potency to warrant use in novel antioxidant formulations.¹⁰

In 2015, Almeida et al. characterized an antioxidant semisolid surfactant-free topical formulation featuring C. sativa leaf extract. In the process of ascertaining the physical, functional, and microbiologic stability of the antioxidant formulation, the investigators identified a hydrating effect and good skin tolerance, which they concluded suggested a capacity to prevent or treat cutaneous conditions in which oxidative stress plays a role.¹¹

Photoprotective potential

In 2010, Sapkota et al. evaluated the antioxidant and antimelanogenic characteristics of several prebloom and full-bloom chestnut flower extracts, finding that a prebloom methanol extract and an ethanol extract evinced the greatest levels of phenolic and flavonoid compounds. These extracts also displayed the best radical scavenging and mushroom tyrosinase–inhibiting activities. Notably, the prebloom extract was effective in protecting the skin from the deleterious impact of UV radiation. The investigators also observed that all of the tested extracts lowered the tyrosinase activity and melanin formation of SK-MEL-2 cells similarly to arbutin. They ascribed the antimelanogenic effects of chestnut flower extracts to their antioxidant-mediated inhibitory effects on tyrosinase. They concluded that chestnut flower extracts have considerable potential as cosmetic agents.¹²

By Wildfeuer/ Wikimedia Commons/ CC BY-SA 3.0

Recently, Almeida et al. studied the protective effects in a human keratinocyte cell line of C. sativa extract at various concentrations (0.001-, 0.01-, 0.05-, and 0.1-mcg/mL) against UV-induced DNA damage. They found that the chestnut extract concentration dependently protected against UV-mediated DNA damage, with the 0.1-mcg/mL concentration affording maximum protection (66.4%). This result was considered to be a direct antioxidant effect attributed to various phenolic antioxidants present in C. sativa. In addition, the investigators observed no phototoxic or genotoxic effects on HaCaT cells incubated with up to 0.1 mcg/mL of chestnut leaf extract. They concluded that C. sativa leaf extract has the potential to prevent or mitigate UV-induced harm to the skin.⁷

Other benefits and bioactivity

Assessments of C. sativa by-products have shown a favorable profile of bioactive constituents that demonstrate antioxidant, anticarcinogenic, and cardioprotective activity. Braga et al. conducted a 2015 review that concluded these compounds, as part of agro-industrial waste, offer value to the pharmaceutical, cosmetics, and food industries, with the potential to lower pollution costs and raise profits while enhancing social, economic, and environmental sustainability in growing regions.¹

A related chestnut species also has been linked to dermatologic uses. In East Asia, a skin firming/antiwrinkle formulation features the inner shell of Castanea crenata as an active ingredient.¹³ In 2002, Chi et al. showed that the chestnut inner shell extract improved cell-associated expression of the adhesion molecules fibronectin and vitronectin. They also found that scoparone (6,7-dimethoxycoumarin) isolated from the chestnut extract exhibited comparable qualities. The investigators concluded that the enhanced expression of adhesion molecules imparted by the chestnut inner shell extract may account for the prevention of cell detachment and the manifestation of antiaging effects.¹³

Allergy

It is worth noting that chestnut is one of the many allergens associated with the latex-fruit syndrome.¹⁴ However, in a patch test investigation of the skin irritation potential of C. sativa leaf extract in 20 volunteers, Almeida et al. identified five phenolic compounds in the extract (chlorogenic acid, ellagic acid, rutin, isoquercitrin, and hyperoside) and found it safe for topical application.⁶ Chestnut is considered to pose a low to moderate risk of inducing allergic reactions.⁹

Conclusion

Recent research appears to suggest the in vitro antioxidant activity of sweet chestnut and potential for use in topical formulations. There remains a paucity of in vivo evidence, however. While much more research is necessary to determine whether it has a place in the dermatologic armamentarium, current data are intriguing.

References

1. Nat Prod Res. 2015;29(1):1-18

2. Biomed Res Int. 2014;2014:232956

3. J Agric Food Chem. 2005 Jan 26;53(2):282-8

4. J Photochem Photobiol B. 2008 May 29;91(2-3):87-95

5. A Modern Herbal (vol. I). New York: Dover Publications, 1971, p. 195

6. Basic Clin Pharmacol Toxicol. 2008 Nov;103(5):461-7

7. J Photochem Photobiol B. 2015 Mar;144C:28-34

8. J Ethnopharmacol. 2014 Aug 8;155(1):463-84

9. J Sci Food Agric. 2010 Aug 15;90(10):1578-89

10. Food Sci Technol Int. 2010 June;16(3):209-16

11. Drug Dev Ind Pharm. 2015 Jan;41(1):148-55

12. Biosci Biotechnol Biochem. 2010;74(8):1527-33

13. Arch Pharm Res. 2002 Aug;25(4):469-74

14. Allergy. 2007 Nov;62(11):1277-81

Dr. Baumann is chief executive officer of the Baumann Cosmetic & Research Institute in the Design District in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann wrote the textbook “Cosmetic Dermatology: Principles and Practice” (New York: McGraw-Hill, 2002), and a book for consumers, “The Skin Type Solution” (New York: Bantam Dell, 2006). Her latest book, “Cosmeceuticals and Cosmetic Ingredients,” was published in November 2014. Dr. Baumann has received funding for clinical grants from Allergan, Aveeno, Avon Products, Evolus, Galderma, GlaxoSmithKline, Kythera Biopharmaceuticals, Mary Kay, Medicis Pharmaceuticals, Neutrogena, Philosophy, Topix Pharmaceuticals, and Unilever.

Terminalia chebula, a member of the Combretaceae family, is an evergreen plant found abundantly in India, Pakistan, China, Thailand, Sri Lanka, and Malaysia.^1,2 It has long been used in traditional medicine, particularly Ayurveda, as well as in Thai traditional medicine.³ It also has also been used for many years in the traditional medicine of the Samahni valley of Pakistan to treat chronic ulcers as well as dental caries and heart ailments.⁴ Other traditional indications include asthma and urinary disorders.⁵ In Thailand, it has been used to treat skin diseases and to promote wound healing and rejuvenation.¹ It is particularly known for its potent antioxidant and antimicrobial properties.⁶ The wide array of health benefits associated with T. chebula is attributed to its high content of phenolic compounds, flavonol glycosides, and other phytonutrients.⁷

Antioxidant, anti-aging, and depigmenting effects

In 2004, Na et al. observed that T. chebula fruit extract exerted an inhibitory effect on the age-dependent shortening of telomeres and UVB-induced oxidative damage in vitro.⁸

Kim et al. screened 50 Korean plants to identify natural sources of elastase and hyaluronidase inhibitors in 2010. The strong efficacy of T. chebula led the investigators to choose it for additional study in which the fruits of the methanol crude extract at 1 mg/mL demonstrated 80% elastase and 87% hyaluronidase inhibitory activities. In addition, the investigators isolated 1,2,3,4,6-penta-O-galloyl-beta-D-glucose (PGG), which also exhibited significant inhibition of elastase and hyaluronidase and induction of type II collagen expression. The authors concluded that PGG has the potential as a cutaneous anti-aging agent posing no cytotoxicity concerns and warrants further in vivo study.⁹

A 2010 in vitro study of the anti-aging properties of the extracts of 15 plant species, including T. chebula galls, outgrowths that result from insect bites, was conducted by Manosroi et al. The cold aqueous extract of T. chebula manifested the highest 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical-scavenging activity and highest stimulation index for proliferation of normal human skin fibroblasts. T. chebula, which also inhibited matrix metalloproteinase (MMP)-2 activity, was compared against compounds such as ascorbic acid, alpha-tocopherol, and butylated hydroxytoluene. The investigators concluded that their findings supported the traditional uses of T. chebula gall in Thai medicine and suggest that T. chebula would be beneficial for inclusion in new anti-aging formulations.³

Later that year, Manosroi et al. characterized the biological activities of the phenolic compounds isolated from T. chebula galls, finding that these compounds (gallic acid, punicalagin, isoterchebulin, 1,3,6-tri-O-galloyl-beta-D-glucopyranose, chebulagic acid, and chebulinic acid) exhibited greater radical-scavenging and melanin-inhibitory activity than the reference compounds ascorbic acid, butylated hydroxytoluene, alpha-tocopherol, arbutin, and kojic acid. Although the T. chebula constituents were less effective than the reference compounds in mushroom tyrosinase inhibition and human tumor cytotoxicity assays, the investigators concluded that the antioxidant and depigmenting activity of the constituents of T. chebula accounted for the beneficial profile of the plant that has emerged over time.¹⁰

The next year, Manosroi et al. assessed the cutaneous anti-aging effects of a gel containing niosomes incorporating a semi-purified fraction including gallic acid derived from T. chebula galls or outgrowths. Human volunteers were enlisted to test skin elasticity and roughness and rabbit skin was used to evaluate skin irritation. The gel containing the semi-purified fractions loaded in niosomes was compared with an unloaded fraction, revealing that the loaded niosomes yielded greater gallic acid chemical stability as well as in vivo anti-aging effects.¹¹ Earlier that year, the team had shown the viability of niosomes, particularly elastic ones, to promote chemical stability for the transdermal absorption of gallic acid in semipurified T. chebula gall fractions in rats. Their findings, they concluded, point to the potential for achieving topical anti-aging benefits from such formulations.¹²

yogesh_more/ Thinkstock.com

In 2012, Akhtar et al. developed a water-in-oil T. chebula formulation and assessed its effects on various parameters. The investigators prepared a base with no active ingredients and a 5% T. chebula formulation, which remained stable at various storage conditions. For 8 weeks, they applied the base as well as the formulation to the cheeks of human volunteers, with weekly evaluations indicating that the formulation as opposed to the base yielded significant improvement, irrespective of time elapsed, in skin moisture content and erythema. The authors concluded that their T. chebula topical cream was effective in rejuvenating human skin.¹³

Wound healing

In 2002, Suguna et al. investigated in vivo the effects of a topically administered alcohol extract of the leaves of T. chebula on the healing of rat dermal wounds. The researchers found that treatment with T. chebula accelerated wound healing, with improved contraction rates and shorter epithelialization periods. T. chebula treatment yielded a 40% increase in the tensile strength of tissues from treated wounds. The authors concluded that T. chebula is beneficial in speeding the wound healing process.²

Immature T. chebula fruit extracts high in tannins are thought to be effective in enhancing the wound healing process, according to Li et al., who found in 2011 that the extracts promoted wound healing in rats, likely due to the antibacterial and angiogenic potency of its tannins.¹

In a 2014 study on wound healing, Singh et al. observed in vitro that T. chebula extracts effectively scavenged free radicals in a DPPH assay and enhanced proliferation of keratinocytes and fibroblasts. They concluded that T. chebula can be considered for use as a bioactive approach to wound healing for its effects in promoting cellular proliferation and inhibiting production of free radicals.⁷

Other biologic activities

A 1995 study by Kurokawa et al. showed that T. chebula was one of four herbal extracts among 10 tested to exhibit a discrete anti–herpes simplex virus type 1 (HSV-1) activity in vitro when combined with acyclovir. Oral administration of the herbs with acyclovir in mice in doses corresponding to human use significantly limited skin lesion development and/or extended mean survival time of infected mice in comparison to any of the herbs or acyclovir used alone.¹⁴

Nam et al. used a 2,4-dinitrofluorobenzene (DNFB)-induced mouse model of atopic symptoms in 2011 and found that a T. chebula seed extract attenuated atopic dermatitis symptoms, resulting in a 52% decrease in the immune response and lower eosinophil levels in nearby skin tissue.⁶

In 2013, Manosroi et al. found that various tannins and one oleanane-type triterpene acid isolated from T. chebula galls displayed strong inhibitory capacity against melanogenesis in mice, with one of the tannins (isoterchebulin) shown to decrease protein levels of tyrosinase, microphthalmia-associated transcription factor, and tyrosine-related protein 1 in mainly a concentration-dependent fashion. Another tannin and several triterpenoids were noted for suppressing 12-O-tetradecanoylphorbol 13-acetate (TPA)-induced inflammation. In addition, constituent phenols manifested strong radical-scavenging activity. In a two-stage carcinogenesis mouse model, the investigators observed that the triterpene acid arjungenin hindered skin tumor promotion after initiation with 7,12-dimethylbenz[a]anthracene (DMBA) and promotion by TPA. Their findings indicate a wide range of biologic activity and potential health benefits associated with T. chebula.¹⁵

In a mouse study in 2014, Singh et al. determined that a new antifungal agent, an apigenin ointment containing extract of T. chebula stem, was effective in significantly reducing the fungal burden from the experimentally-induced dermatophyte Trichopython mentagrophytes. They suggested that this agent warrants consideration in clinically treating dermatophytosis in humans.¹⁶

Triphala, a traditional combination formulation

Long used in Ayurveda, triphala (the word is derived from the Sanskrit tri, three, and phala, fruits) is an antioxidant-rich herbal formulation that combines the dried fruits of T. chebula, Terminalia bellirica, and Emblica officinalis. Naik et al. observed, in a 2005 in vitro study of the aqueous extract of the fruits of T. chebula, T. bellirica, and E. officinalis, as well as their equiproportional mixture triphala, that T. chebula was the most effective at scavenging free radicals. They noted that triphala appears to synergistically combine the strengths of each of its primary components.¹⁷ Subsequent studies have demonstrated that triphala is a strong source of natural antioxidants and exhibits a wide range of beneficial activities, including free radical scavenging, antioxidant, anti-inflammatory, analgesic, antibacterial, antimutagenic, wound healing, antistress, adaptogenic, hypoglycemic, anticancer, chemoprotective, radioprotective, chemopreventive, and wound healing.^5,18-21

Extracts of T. chebula also have been combined with those of E. officinalis, T. bellirica, Albizia lebbeck, Piper nigrum, Zingiber officinale, and Piper longum in a polyherbal formulation (Aller-7/NR-A2) that has been found safe for the treatment of allergic rhinitis.²²

Conclusion

The use of T. chebula in various traditional medical practices around the world is well established. There is ample evidence supporting multiple biologic properties of this Ayurvedic staple. While it is not a standard ingredient in dermatologic health care in the West, the data support continued research as to how best to incorporate this agent.

References

1. BMC Complement Altern Med. 2011 Oct 7;11:86.

2. Phytother Res. 2002 May;16(3):227-31.

3. Pharm Biol. 2010 Apr;48(4):469-81.

4. Pak J Biol Sci. 2007 Jul 1;10(13):2241-56.

5. BMC Complement Altern Med. 2010 May 13;10:20.

6. Int J Mol Med. 2011 Dec;28(6):1013-8.

7. Evid Based Complement Alternat Med. 2014;2014:701656.

8. Phytother Res. 2004 Sep;18:737-41.

9. Acta Pol Pharm. 2010 Mar-Apr;67(2):145-50.

10. Nat Prod Res. 2010 Dec;24(20):1915-26.

11. Pharm Biol. 2011 Nov;49(11):1190-203.

12. Pharm Biol. 2011 Jun;49(6):553-62.

13. Forsch Komplementmed. 2012;19(1):20-5.

14. Antiviral Res. 1995 May;27(1-2):19-37.

15. Chem Biodivers. 2013 Aug;10(8):1448-63.

16. Mycoses. 2014 Aug;57(8):497-506.

17. Phytother Res. 2005 Jul;19(7):582-6.

18. Chin J Integr Med. 2012 Dec;18(12):946-54.

19. J Surg Res. 2008 Jan;144(1):94-101.

20. J Surg Res. 2010 Jan;158(1):162-70.

21. J Altern Complement Med. 2010 Dec;16(12):1301-8.

22. Toxicol Mech Methods. 2005;15(3):193-204.

Dr. Baumann is chief executive officer of the Baumann Cosmetic & Research Institute in the Design District in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann wrote the textbook, “Cosmetic Dermatology: Principles and Practice” (New York: McGraw-Hill, 2002), and a book for consumers, “The Skin Type Solution” (New York: Bantam Dell, 2006). She has contributed to the Cosmeceutical Critique column in Dermatology News since January 2001. Her latest book, “Cosmeceuticals and Cosmetic Ingredients,” was published in November 2014. Dr. Baumann has received funding for clinical grants from Allergan, Aveeno, Avon Products, Evolus, Galderma, GlaxoSmithKline, Kythera Biopharmaceuticals, Mary Kay, Medicis Pharmaceuticals, Neutrogena, Philosophy, Topix Pharmaceuticals, and Unilever.

Terminalia chebula, a member of the Combretaceae family, is an evergreen plant found abundantly in India, Pakistan, China, Thailand, Sri Lanka, and Malaysia.^1,2 It has long been used in traditional medicine, particularly Ayurveda, as well as in Thai traditional medicine.³ It also has also been used for many years in the traditional medicine of the Samahni valley of Pakistan to treat chronic ulcers as well as dental caries and heart ailments.⁴ Other traditional indications include asthma and urinary disorders.⁵ In Thailand, it has been used to treat skin diseases and to promote wound healing and rejuvenation.¹ It is particularly known for its potent antioxidant and antimicrobial properties.⁶ The wide array of health benefits associated with T. chebula is attributed to its high content of phenolic compounds, flavonol glycosides, and other phytonutrients.⁷

Antioxidant, anti-aging, and depigmenting effects

In 2004, Na et al. observed that T. chebula fruit extract exerted an inhibitory effect on the age-dependent shortening of telomeres and UVB-induced oxidative damage in vitro.⁸

Kim et al. screened 50 Korean plants to identify natural sources of elastase and hyaluronidase inhibitors in 2010. The strong efficacy of T. chebula led the investigators to choose it for additional study in which the fruits of the methanol crude extract at 1 mg/mL demonstrated 80% elastase and 87% hyaluronidase inhibitory activities. In addition, the investigators isolated 1,2,3,4,6-penta-O-galloyl-beta-D-glucose (PGG), which also exhibited significant inhibition of elastase and hyaluronidase and induction of type II collagen expression. The authors concluded that PGG has the potential as a cutaneous anti-aging agent posing no cytotoxicity concerns and warrants further in vivo study.⁹

A 2010 in vitro study of the anti-aging properties of the extracts of 15 plant species, including T. chebula galls, outgrowths that result from insect bites, was conducted by Manosroi et al. The cold aqueous extract of T. chebula manifested the highest 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical-scavenging activity and highest stimulation index for proliferation of normal human skin fibroblasts. T. chebula, which also inhibited matrix metalloproteinase (MMP)-2 activity, was compared against compounds such as ascorbic acid, alpha-tocopherol, and butylated hydroxytoluene. The investigators concluded that their findings supported the traditional uses of T. chebula gall in Thai medicine and suggest that T. chebula would be beneficial for inclusion in new anti-aging formulations.³

Later that year, Manosroi et al. characterized the biological activities of the phenolic compounds isolated from T. chebula galls, finding that these compounds (gallic acid, punicalagin, isoterchebulin, 1,3,6-tri-O-galloyl-beta-D-glucopyranose, chebulagic acid, and chebulinic acid) exhibited greater radical-scavenging and melanin-inhibitory activity than the reference compounds ascorbic acid, butylated hydroxytoluene, alpha-tocopherol, arbutin, and kojic acid. Although the T. chebula constituents were less effective than the reference compounds in mushroom tyrosinase inhibition and human tumor cytotoxicity assays, the investigators concluded that the antioxidant and depigmenting activity of the constituents of T. chebula accounted for the beneficial profile of the plant that has emerged over time.¹⁰

The next year, Manosroi et al. assessed the cutaneous anti-aging effects of a gel containing niosomes incorporating a semi-purified fraction including gallic acid derived from T. chebula galls or outgrowths. Human volunteers were enlisted to test skin elasticity and roughness and rabbit skin was used to evaluate skin irritation. The gel containing the semi-purified fractions loaded in niosomes was compared with an unloaded fraction, revealing that the loaded niosomes yielded greater gallic acid chemical stability as well as in vivo anti-aging effects.¹¹ Earlier that year, the team had shown the viability of niosomes, particularly elastic ones, to promote chemical stability for the transdermal absorption of gallic acid in semipurified T. chebula gall fractions in rats. Their findings, they concluded, point to the potential for achieving topical anti-aging benefits from such formulations.¹²

yogesh_more/ Thinkstock.com

In 2012, Akhtar et al. developed a water-in-oil T. chebula formulation and assessed its effects on various parameters. The investigators prepared a base with no active ingredients and a 5% T. chebula formulation, which remained stable at various storage conditions. For 8 weeks, they applied the base as well as the formulation to the cheeks of human volunteers, with weekly evaluations indicating that the formulation as opposed to the base yielded significant improvement, irrespective of time elapsed, in skin moisture content and erythema. The authors concluded that their T. chebula topical cream was effective in rejuvenating human skin.¹³

Wound healing

In 2002, Suguna et al. investigated in vivo the effects of a topically administered alcohol extract of the leaves of T. chebula on the healing of rat dermal wounds. The researchers found that treatment with T. chebula accelerated wound healing, with improved contraction rates and shorter epithelialization periods. T. chebula treatment yielded a 40% increase in the tensile strength of tissues from treated wounds. The authors concluded that T. chebula is beneficial in speeding the wound healing process.²

Immature T. chebula fruit extracts high in tannins are thought to be effective in enhancing the wound healing process, according to Li et al., who found in 2011 that the extracts promoted wound healing in rats, likely due to the antibacterial and angiogenic potency of its tannins.¹

In a 2014 study on wound healing, Singh et al. observed in vitro that T. chebula extracts effectively scavenged free radicals in a DPPH assay and enhanced proliferation of keratinocytes and fibroblasts. They concluded that T. chebula can be considered for use as a bioactive approach to wound healing for its effects in promoting cellular proliferation and inhibiting production of free radicals.⁷

Other biologic activities

A 1995 study by Kurokawa et al. showed that T. chebula was one of four herbal extracts among 10 tested to exhibit a discrete anti–herpes simplex virus type 1 (HSV-1) activity in vitro when combined with acyclovir. Oral administration of the herbs with acyclovir in mice in doses corresponding to human use significantly limited skin lesion development and/or extended mean survival time of infected mice in comparison to any of the herbs or acyclovir used alone.¹⁴

Nam et al. used a 2,4-dinitrofluorobenzene (DNFB)-induced mouse model of atopic symptoms in 2011 and found that a T. chebula seed extract attenuated atopic dermatitis symptoms, resulting in a 52% decrease in the immune response and lower eosinophil levels in nearby skin tissue.⁶

In 2013, Manosroi et al. found that various tannins and one oleanane-type triterpene acid isolated from T. chebula galls displayed strong inhibitory capacity against melanogenesis in mice, with one of the tannins (isoterchebulin) shown to decrease protein levels of tyrosinase, microphthalmia-associated transcription factor, and tyrosine-related protein 1 in mainly a concentration-dependent fashion. Another tannin and several triterpenoids were noted for suppressing 12-O-tetradecanoylphorbol 13-acetate (TPA)-induced inflammation. In addition, constituent phenols manifested strong radical-scavenging activity. In a two-stage carcinogenesis mouse model, the investigators observed that the triterpene acid arjungenin hindered skin tumor promotion after initiation with 7,12-dimethylbenz[a]anthracene (DMBA) and promotion by TPA. Their findings indicate a wide range of biologic activity and potential health benefits associated with T. chebula.¹⁵

In a mouse study in 2014, Singh et al. determined that a new antifungal agent, an apigenin ointment containing extract of T. chebula stem, was effective in significantly reducing the fungal burden from the experimentally-induced dermatophyte Trichopython mentagrophytes. They suggested that this agent warrants consideration in clinically treating dermatophytosis in humans.¹⁶

Triphala, a traditional combination formulation

Long used in Ayurveda, triphala (the word is derived from the Sanskrit tri, three, and phala, fruits) is an antioxidant-rich herbal formulation that combines the dried fruits of T. chebula, Terminalia bellirica, and Emblica officinalis. Naik et al. observed, in a 2005 in vitro study of the aqueous extract of the fruits of T. chebula, T. bellirica, and E. officinalis, as well as their equiproportional mixture triphala, that T. chebula was the most effective at scavenging free radicals. They noted that triphala appears to synergistically combine the strengths of each of its primary components.¹⁷ Subsequent studies have demonstrated that triphala is a strong source of natural antioxidants and exhibits a wide range of beneficial activities, including free radical scavenging, antioxidant, anti-inflammatory, analgesic, antibacterial, antimutagenic, wound healing, antistress, adaptogenic, hypoglycemic, anticancer, chemoprotective, radioprotective, chemopreventive, and wound healing.^5,18-21

Extracts of T. chebula also have been combined with those of E. officinalis, T. bellirica, Albizia lebbeck, Piper nigrum, Zingiber officinale, and Piper longum in a polyherbal formulation (Aller-7/NR-A2) that has been found safe for the treatment of allergic rhinitis.²²

Conclusion

The use of T. chebula in various traditional medical practices around the world is well established. There is ample evidence supporting multiple biologic properties of this Ayurvedic staple. While it is not a standard ingredient in dermatologic health care in the West, the data support continued research as to how best to incorporate this agent.

References

1. BMC Complement Altern Med. 2011 Oct 7;11:86.

2. Phytother Res. 2002 May;16(3):227-31.

3. Pharm Biol. 2010 Apr;48(4):469-81.

4. Pak J Biol Sci. 2007 Jul 1;10(13):2241-56.

5. BMC Complement Altern Med. 2010 May 13;10:20.

6. Int J Mol Med. 2011 Dec;28(6):1013-8.

7. Evid Based Complement Alternat Med. 2014;2014:701656.

8. Phytother Res. 2004 Sep;18:737-41.

9. Acta Pol Pharm. 2010 Mar-Apr;67(2):145-50.

10. Nat Prod Res. 2010 Dec;24(20):1915-26.

11. Pharm Biol. 2011 Nov;49(11):1190-203.

12. Pharm Biol. 2011 Jun;49(6):553-62.

13. Forsch Komplementmed. 2012;19(1):20-5.

14. Antiviral Res. 1995 May;27(1-2):19-37.

15. Chem Biodivers. 2013 Aug;10(8):1448-63.

16. Mycoses. 2014 Aug;57(8):497-506.

17. Phytother Res. 2005 Jul;19(7):582-6.

18. Chin J Integr Med. 2012 Dec;18(12):946-54.

19. J Surg Res. 2008 Jan;144(1):94-101.

20. J Surg Res. 2010 Jan;158(1):162-70.

21. J Altern Complement Med. 2010 Dec;16(12):1301-8.

22. Toxicol Mech Methods. 2005;15(3):193-204.

Dr. Baumann is chief executive officer of the Baumann Cosmetic & Research Institute in the Design District in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann wrote the textbook, “Cosmetic Dermatology: Principles and Practice” (New York: McGraw-Hill, 2002), and a book for consumers, “The Skin Type Solution” (New York: Bantam Dell, 2006). She has contributed to the Cosmeceutical Critique column in Dermatology News since January 2001. Her latest book, “Cosmeceuticals and Cosmetic Ingredients,” was published in November 2014. Dr. Baumann has received funding for clinical grants from Allergan, Aveeno, Avon Products, Evolus, Galderma, GlaxoSmithKline, Kythera Biopharmaceuticals, Mary Kay, Medicis Pharmaceuticals, Neutrogena, Philosophy, Topix Pharmaceuticals, and Unilever.

Terminalia chebula, a member of the Combretaceae family, is an evergreen plant found abundantly in India, Pakistan, China, Thailand, Sri Lanka, and Malaysia.^1,2 It has long been used in traditional medicine, particularly Ayurveda, as well as in Thai traditional medicine.³ It also has also been used for many years in the traditional medicine of the Samahni valley of Pakistan to treat chronic ulcers as well as dental caries and heart ailments.⁴ Other traditional indications include asthma and urinary disorders.⁵ In Thailand, it has been used to treat skin diseases and to promote wound healing and rejuvenation.¹ It is particularly known for its potent antioxidant and antimicrobial properties.⁶ The wide array of health benefits associated with T. chebula is attributed to its high content of phenolic compounds, flavonol glycosides, and other phytonutrients.⁷

Antioxidant, anti-aging, and depigmenting effects

In 2004, Na et al. observed that T. chebula fruit extract exerted an inhibitory effect on the age-dependent shortening of telomeres and UVB-induced oxidative damage in vitro.⁸

Kim et al. screened 50 Korean plants to identify natural sources of elastase and hyaluronidase inhibitors in 2010. The strong efficacy of T. chebula led the investigators to choose it for additional study in which the fruits of the methanol crude extract at 1 mg/mL demonstrated 80% elastase and 87% hyaluronidase inhibitory activities. In addition, the investigators isolated 1,2,3,4,6-penta-O-galloyl-beta-D-glucose (PGG), which also exhibited significant inhibition of elastase and hyaluronidase and induction of type II collagen expression. The authors concluded that PGG has the potential as a cutaneous anti-aging agent posing no cytotoxicity concerns and warrants further in vivo study.⁹

A 2010 in vitro study of the anti-aging properties of the extracts of 15 plant species, including T. chebula galls, outgrowths that result from insect bites, was conducted by Manosroi et al. The cold aqueous extract of T. chebula manifested the highest 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical-scavenging activity and highest stimulation index for proliferation of normal human skin fibroblasts. T. chebula, which also inhibited matrix metalloproteinase (MMP)-2 activity, was compared against compounds such as ascorbic acid, alpha-tocopherol, and butylated hydroxytoluene. The investigators concluded that their findings supported the traditional uses of T. chebula gall in Thai medicine and suggest that T. chebula would be beneficial for inclusion in new anti-aging formulations.³

Later that year, Manosroi et al. characterized the biological activities of the phenolic compounds isolated from T. chebula galls, finding that these compounds (gallic acid, punicalagin, isoterchebulin, 1,3,6-tri-O-galloyl-beta-D-glucopyranose, chebulagic acid, and chebulinic acid) exhibited greater radical-scavenging and melanin-inhibitory activity than the reference compounds ascorbic acid, butylated hydroxytoluene, alpha-tocopherol, arbutin, and kojic acid. Although the T. chebula constituents were less effective than the reference compounds in mushroom tyrosinase inhibition and human tumor cytotoxicity assays, the investigators concluded that the antioxidant and depigmenting activity of the constituents of T. chebula accounted for the beneficial profile of the plant that has emerged over time.¹⁰

The next year, Manosroi et al. assessed the cutaneous anti-aging effects of a gel containing niosomes incorporating a semi-purified fraction including gallic acid derived from T. chebula galls or outgrowths. Human volunteers were enlisted to test skin elasticity and roughness and rabbit skin was used to evaluate skin irritation. The gel containing the semi-purified fractions loaded in niosomes was compared with an unloaded fraction, revealing that the loaded niosomes yielded greater gallic acid chemical stability as well as in vivo anti-aging effects.¹¹ Earlier that year, the team had shown the viability of niosomes, particularly elastic ones, to promote chemical stability for the transdermal absorption of gallic acid in semipurified T. chebula gall fractions in rats. Their findings, they concluded, point to the potential for achieving topical anti-aging benefits from such formulations.¹²

yogesh_more/ Thinkstock.com

In 2012, Akhtar et al. developed a water-in-oil T. chebula formulation and assessed its effects on various parameters. The investigators prepared a base with no active ingredients and a 5% T. chebula formulation, which remained stable at various storage conditions. For 8 weeks, they applied the base as well as the formulation to the cheeks of human volunteers, with weekly evaluations indicating that the formulation as opposed to the base yielded significant improvement, irrespective of time elapsed, in skin moisture content and erythema. The authors concluded that their T. chebula topical cream was effective in rejuvenating human skin.¹³

Wound healing

In 2002, Suguna et al. investigated in vivo the effects of a topically administered alcohol extract of the leaves of T. chebula on the healing of rat dermal wounds. The researchers found that treatment with T. chebula accelerated wound healing, with improved contraction rates and shorter epithelialization periods. T. chebula treatment yielded a 40% increase in the tensile strength of tissues from treated wounds. The authors concluded that T. chebula is beneficial in speeding the wound healing process.²

Immature T. chebula fruit extracts high in tannins are thought to be effective in enhancing the wound healing process, according to Li et al., who found in 2011 that the extracts promoted wound healing in rats, likely due to the antibacterial and angiogenic potency of its tannins.¹

In a 2014 study on wound healing, Singh et al. observed in vitro that T. chebula extracts effectively scavenged free radicals in a DPPH assay and enhanced proliferation of keratinocytes and fibroblasts. They concluded that T. chebula can be considered for use as a bioactive approach to wound healing for its effects in promoting cellular proliferation and inhibiting production of free radicals.⁷

Other biologic activities

A 1995 study by Kurokawa et al. showed that T. chebula was one of four herbal extracts among 10 tested to exhibit a discrete anti–herpes simplex virus type 1 (HSV-1) activity in vitro when combined with acyclovir. Oral administration of the herbs with acyclovir in mice in doses corresponding to human use significantly limited skin lesion development and/or extended mean survival time of infected mice in comparison to any of the herbs or acyclovir used alone.¹⁴

Nam et al. used a 2,4-dinitrofluorobenzene (DNFB)-induced mouse model of atopic symptoms in 2011 and found that a T. chebula seed extract attenuated atopic dermatitis symptoms, resulting in a 52% decrease in the immune response and lower eosinophil levels in nearby skin tissue.⁶

In 2013, Manosroi et al. found that various tannins and one oleanane-type triterpene acid isolated from T. chebula galls displayed strong inhibitory capacity against melanogenesis in mice, with one of the tannins (isoterchebulin) shown to decrease protein levels of tyrosinase, microphthalmia-associated transcription factor, and tyrosine-related protein 1 in mainly a concentration-dependent fashion. Another tannin and several triterpenoids were noted for suppressing 12-O-tetradecanoylphorbol 13-acetate (TPA)-induced inflammation. In addition, constituent phenols manifested strong radical-scavenging activity. In a two-stage carcinogenesis mouse model, the investigators observed that the triterpene acid arjungenin hindered skin tumor promotion after initiation with 7,12-dimethylbenz[a]anthracene (DMBA) and promotion by TPA. Their findings indicate a wide range of biologic activity and potential health benefits associated with T. chebula.¹⁵

In a mouse study in 2014, Singh et al. determined that a new antifungal agent, an apigenin ointment containing extract of T. chebula stem, was effective in significantly reducing the fungal burden from the experimentally-induced dermatophyte Trichopython mentagrophytes. They suggested that this agent warrants consideration in clinically treating dermatophytosis in humans.¹⁶

Triphala, a traditional combination formulation

Long used in Ayurveda, triphala (the word is derived from the Sanskrit tri, three, and phala, fruits) is an antioxidant-rich herbal formulation that combines the dried fruits of T. chebula, Terminalia bellirica, and Emblica officinalis. Naik et al. observed, in a 2005 in vitro study of the aqueous extract of the fruits of T. chebula, T. bellirica, and E. officinalis, as well as their equiproportional mixture triphala, that T. chebula was the most effective at scavenging free radicals. They noted that triphala appears to synergistically combine the strengths of each of its primary components.¹⁷ Subsequent studies have demonstrated that triphala is a strong source of natural antioxidants and exhibits a wide range of beneficial activities, including free radical scavenging, antioxidant, anti-inflammatory, analgesic, antibacterial, antimutagenic, wound healing, antistress, adaptogenic, hypoglycemic, anticancer, chemoprotective, radioprotective, chemopreventive, and wound healing.^5,18-21

Extracts of T. chebula also have been combined with those of E. officinalis, T. bellirica, Albizia lebbeck, Piper nigrum, Zingiber officinale, and Piper longum in a polyherbal formulation (Aller-7/NR-A2) that has been found safe for the treatment of allergic rhinitis.²²

Conclusion

The use of T. chebula in various traditional medical practices around the world is well established. There is ample evidence supporting multiple biologic properties of this Ayurvedic staple. While it is not a standard ingredient in dermatologic health care in the West, the data support continued research as to how best to incorporate this agent.

References

1. BMC Complement Altern Med. 2011 Oct 7;11:86.

2. Phytother Res. 2002 May;16(3):227-31.

3. Pharm Biol. 2010 Apr;48(4):469-81.

4. Pak J Biol Sci. 2007 Jul 1;10(13):2241-56.

5. BMC Complement Altern Med. 2010 May 13;10:20.

6. Int J Mol Med. 2011 Dec;28(6):1013-8.

7. Evid Based Complement Alternat Med. 2014;2014:701656.

8. Phytother Res. 2004 Sep;18:737-41.

9. Acta Pol Pharm. 2010 Mar-Apr;67(2):145-50.

10. Nat Prod Res. 2010 Dec;24(20):1915-26.

11. Pharm Biol. 2011 Nov;49(11):1190-203.

12. Pharm Biol. 2011 Jun;49(6):553-62.

13. Forsch Komplementmed. 2012;19(1):20-5.

14. Antiviral Res. 1995 May;27(1-2):19-37.

15. Chem Biodivers. 2013 Aug;10(8):1448-63.

16. Mycoses. 2014 Aug;57(8):497-506.

17. Phytother Res. 2005 Jul;19(7):582-6.

18. Chin J Integr Med. 2012 Dec;18(12):946-54.

19. J Surg Res. 2008 Jan;144(1):94-101.

20. J Surg Res. 2010 Jan;158(1):162-70.

21. J Altern Complement Med. 2010 Dec;16(12):1301-8.

22. Toxicol Mech Methods. 2005;15(3):193-204.

Dr. Baumann is chief executive officer of the Baumann Cosmetic & Research Institute in the Design District in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann wrote the textbook, “Cosmetic Dermatology: Principles and Practice” (New York: McGraw-Hill, 2002), and a book for consumers, “The Skin Type Solution” (New York: Bantam Dell, 2006). She has contributed to the Cosmeceutical Critique column in Dermatology News since January 2001. Her latest book, “Cosmeceuticals and Cosmetic Ingredients,” was published in November 2014. Dr. Baumann has received funding for clinical grants from Allergan, Aveeno, Avon Products, Evolus, Galderma, GlaxoSmithKline, Kythera Biopharmaceuticals, Mary Kay, Medicis Pharmaceuticals, Neutrogena, Philosophy, Topix Pharmaceuticals, and Unilever.

Terminalia chebula, a member of the Combretaceae family, is an evergreen plant found abundantly in India, Pakistan, China, Thailand, Sri Lanka, and Malaysia.^1,2 It has long been used in traditional medicine, particularly Ayurveda, as well as in Thai traditional medicine.³ It also has also been used for many years in the traditional medicine of the Samahni valley of Pakistan to treat chronic ulcers as well as dental caries and heart ailments.⁴ Other traditional indications include asthma and urinary disorders.⁵ In Thailand, it has been used to treat skin diseases and to promote wound healing and rejuvenation.¹ It is particularly known for its potent antioxidant and antimicrobial properties.⁶ The wide array of health benefits associated with T. chebula is attributed to its high content of phenolic compounds, flavonol glycosides, and other phytonutrients.⁷

Antioxidant, anti-aging, and depigmenting effects

In 2004, Na et al. observed that T. chebula fruit extract exerted an inhibitory effect on the age-dependent shortening of telomeres and UVB-induced oxidative damage in vitro.⁸

Kim et al. screened 50 Korean plants to identify natural sources of elastase and hyaluronidase inhibitors in 2010. The strong efficacy of T. chebula led the investigators to choose it for additional study in which the fruits of the methanol crude extract at 1 mg/mL demonstrated 80% elastase and 87% hyaluronidase inhibitory activities. In addition, the investigators isolated 1,2,3,4,6-penta-O-galloyl-beta-D-glucose (PGG), which also exhibited significant inhibition of elastase and hyaluronidase and induction of type II collagen expression. The authors concluded that PGG has the potential as a cutaneous anti-aging agent posing no cytotoxicity concerns and warrants further in vivo study.⁹

A 2010 in vitro study of the anti-aging properties of the extracts of 15 plant species, including T. chebula galls, outgrowths that result from insect bites, was conducted by Manosroi et al. The cold aqueous extract of T. chebula manifested the highest 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical-scavenging activity and highest stimulation index for proliferation of normal human skin fibroblasts. T. chebula, which also inhibited matrix metalloproteinase (MMP)-2 activity, was compared against compounds such as ascorbic acid, alpha-tocopherol, and butylated hydroxytoluene. The investigators concluded that their findings supported the traditional uses of T. chebula gall in Thai medicine and suggest that T. chebula would be beneficial for inclusion in new anti-aging formulations.³

Later that year, Manosroi et al. characterized the biological activities of the phenolic compounds isolated from T. chebula galls, finding that these compounds (gallic acid, punicalagin, isoterchebulin, 1,3,6-tri-O-galloyl-beta-D-glucopyranose, chebulagic acid, and chebulinic acid) exhibited greater radical-scavenging and melanin-inhibitory activity than the reference compounds ascorbic acid, butylated hydroxytoluene, alpha-tocopherol, arbutin, and kojic acid. Although the T. chebula constituents were less effective than the reference compounds in mushroom tyrosinase inhibition and human tumor cytotoxicity assays, the investigators concluded that the antioxidant and depigmenting activity of the constituents of T. chebula accounted for the beneficial profile of the plant that has emerged over time.¹⁰

The next year, Manosroi et al. assessed the cutaneous anti-aging effects of a gel containing niosomes incorporating a semi-purified fraction including gallic acid derived from T. chebula galls or outgrowths. Human volunteers were enlisted to test skin elasticity and roughness and rabbit skin was used to evaluate skin irritation. The gel containing the semi-purified fractions loaded in niosomes was compared with an unloaded fraction, revealing that the loaded niosomes yielded greater gallic acid chemical stability as well as in vivo anti-aging effects.¹¹ Earlier that year, the team had shown the viability of niosomes, particularly elastic ones, to promote chemical stability for the transdermal absorption of gallic acid in semipurified T. chebula gall fractions in rats. Their findings, they concluded, point to the potential for achieving topical anti-aging benefits from such formulations.¹²

yogesh_more/ Thinkstock.com

In 2012, Akhtar et al. developed a water-in-oil T. chebula formulation and assessed its effects on various parameters. The investigators prepared a base with no active ingredients and a 5% T. chebula formulation, which remained stable at various storage conditions. For 8 weeks, they applied the base as well as the formulation to the cheeks of human volunteers, with weekly evaluations indicating that the formulation as opposed to the base yielded significant improvement, irrespective of time elapsed, in skin moisture content and erythema. The authors concluded that their T. chebula topical cream was effective in rejuvenating human skin.¹³

Wound healing

In 2002, Suguna et al. investigated in vivo the effects of a topically administered alcohol extract of the leaves of T. chebula on the healing of rat dermal wounds. The researchers found that treatment with T. chebula accelerated wound healing, with improved contraction rates and shorter epithelialization periods. T. chebula treatment yielded a 40% increase in the tensile strength of tissues from treated wounds. The authors concluded that T. chebula is beneficial in speeding the wound healing process.²

Immature T. chebula fruit extracts high in tannins are thought to be effective in enhancing the wound healing process, according to Li et al., who found in 2011 that the extracts promoted wound healing in rats, likely due to the antibacterial and angiogenic potency of its tannins.¹

In a 2014 study on wound healing, Singh et al. observed in vitro that T. chebula extracts effectively scavenged free radicals in a DPPH assay and enhanced proliferation of keratinocytes and fibroblasts. They concluded that T. chebula can be considered for use as a bioactive approach to wound healing for its effects in promoting cellular proliferation and inhibiting production of free radicals.⁷

Other biologic activities

A 1995 study by Kurokawa et al. showed that T. chebula was one of four herbal extracts among 10 tested to exhibit a discrete anti–herpes simplex virus type 1 (HSV-1) activity in vitro when combined with acyclovir. Oral administration of the herbs with acyclovir in mice in doses corresponding to human use significantly limited skin lesion development and/or extended mean survival time of infected mice in comparison to any of the herbs or acyclovir used alone.¹⁴

Nam et al. used a 2,4-dinitrofluorobenzene (DNFB)-induced mouse model of atopic symptoms in 2011 and found that a T. chebula seed extract attenuated atopic dermatitis symptoms, resulting in a 52% decrease in the immune response and lower eosinophil levels in nearby skin tissue.⁶

In 2013, Manosroi et al. found that various tannins and one oleanane-type triterpene acid isolated from T. chebula galls displayed strong inhibitory capacity against melanogenesis in mice, with one of the tannins (isoterchebulin) shown to decrease protein levels of tyrosinase, microphthalmia-associated transcription factor, and tyrosine-related protein 1 in mainly a concentration-dependent fashion. Another tannin and several triterpenoids were noted for suppressing 12-O-tetradecanoylphorbol 13-acetate (TPA)-induced inflammation. In addition, constituent phenols manifested strong radical-scavenging activity. In a two-stage carcinogenesis mouse model, the investigators observed that the triterpene acid arjungenin hindered skin tumor promotion after initiation with 7,12-dimethylbenz[a]anthracene (DMBA) and promotion by TPA. Their findings indicate a wide range of biologic activity and potential health benefits associated with T. chebula.¹⁵

In a mouse study in 2014, Singh et al. determined that a new antifungal agent, an apigenin ointment containing extract of T. chebula stem, was effective in significantly reducing the fungal burden from the experimentally-induced dermatophyte Trichopython mentagrophytes. They suggested that this agent warrants consideration in clinically treating dermatophytosis in humans.¹⁶

Triphala, a traditional combination formulation

Long used in Ayurveda, triphala (the word is derived from the Sanskrit tri, three, and phala, fruits) is an antioxidant-rich herbal formulation that combines the dried fruits of T. chebula, Terminalia bellirica, and Emblica officinalis. Naik et al. observed, in a 2005 in vitro study of the aqueous extract of the fruits of T. chebula, T. bellirica, and E. officinalis, as well as their equiproportional mixture triphala, that T. chebula was the most effective at scavenging free radicals. They noted that triphala appears to synergistically combine the strengths of each of its primary components.¹⁷ Subsequent studies have demonstrated that triphala is a strong source of natural antioxidants and exhibits a wide range of beneficial activities, including free radical scavenging, antioxidant, anti-inflammatory, analgesic, antibacterial, antimutagenic, wound healing, antistress, adaptogenic, hypoglycemic, anticancer, chemoprotective, radioprotective, chemopreventive, and wound healing.^5,18-21

Extracts of T. chebula also have been combined with those of E. officinalis, T. bellirica, Albizia lebbeck, Piper nigrum, Zingiber officinale, and Piper longum in a polyherbal formulation (Aller-7/NR-A2) that has been found safe for the treatment of allergic rhinitis.²²

Conclusion

The use of T. chebula in various traditional medical practices around the world is well established. There is ample evidence supporting multiple biologic properties of this Ayurvedic staple. While it is not a standard ingredient in dermatologic health care in the West, the data support continued research as to how best to incorporate this agent.

References

1. BMC Complement Altern Med. 2011 Oct 7;11:86.

2. Phytother Res. 2002 May;16(3):227-31.

3. Pharm Biol. 2010 Apr;48(4):469-81.

4. Pak J Biol Sci. 2007 Jul 1;10(13):2241-56.

5. BMC Complement Altern Med. 2010 May 13;10:20.

6. Int J Mol Med. 2011 Dec;28(6):1013-8.

7. Evid Based Complement Alternat Med. 2014;2014:701656.

8. Phytother Res. 2004 Sep;18:737-41.

9. Acta Pol Pharm. 2010 Mar-Apr;67(2):145-50.

10. Nat Prod Res. 2010 Dec;24(20):1915-26.

11. Pharm Biol. 2011 Nov;49(11):1190-203.

12. Pharm Biol. 2011 Jun;49(6):553-62.

13. Forsch Komplementmed. 2012;19(1):20-5.

14. Antiviral Res. 1995 May;27(1-2):19-37.

15. Chem Biodivers. 2013 Aug;10(8):1448-63.

16. Mycoses. 2014 Aug;57(8):497-506.

17. Phytother Res. 2005 Jul;19(7):582-6.

18. Chin J Integr Med. 2012 Dec;18(12):946-54.

19. J Surg Res. 2008 Jan;144(1):94-101.

20. J Surg Res. 2010 Jan;158(1):162-70.

21. J Altern Complement Med. 2010 Dec;16(12):1301-8.

22. Toxicol Mech Methods. 2005;15(3):193-204.

Dr. Baumann is chief executive officer of the Baumann Cosmetic & Research Institute in the Design District in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann wrote the textbook, “Cosmetic Dermatology: Principles and Practice” (New York: McGraw-Hill, 2002), and a book for consumers, “The Skin Type Solution” (New York: Bantam Dell, 2006). She has contributed to the Cosmeceutical Critique column in Dermatology News since January 2001. Her latest book, “Cosmeceuticals and Cosmetic Ingredients,” was published in November 2014. Dr. Baumann has received funding for clinical grants from Allergan, Aveeno, Avon Products, Evolus, Galderma, GlaxoSmithKline, Kythera Biopharmaceuticals, Mary Kay, Medicis Pharmaceuticals, Neutrogena, Philosophy, Topix Pharmaceuticals, and Unilever.

Terminalia chebula, a member of the Combretaceae family, is an evergreen plant found abundantly in India, Pakistan, China, Thailand, Sri Lanka, and Malaysia.^1,2 It has long been used in traditional medicine, particularly Ayurveda, as well as in Thai traditional medicine.³ It also has also been used for many years in the traditional medicine of the Samahni valley of Pakistan to treat chronic ulcers as well as dental caries and heart ailments.⁴ Other traditional indications include asthma and urinary disorders.⁵ In Thailand, it has been used to treat skin diseases and to promote wound healing and rejuvenation.¹ It is particularly known for its potent antioxidant and antimicrobial properties.⁶ The wide array of health benefits associated with T. chebula is attributed to its high content of phenolic compounds, flavonol glycosides, and other phytonutrients.⁷

Antioxidant, anti-aging, and depigmenting effects

In 2004, Na et al. observed that T. chebula fruit extract exerted an inhibitory effect on the age-dependent shortening of telomeres and UVB-induced oxidative damage in vitro.⁸

Kim et al. screened 50 Korean plants to identify natural sources of elastase and hyaluronidase inhibitors in 2010. The strong efficacy of T. chebula led the investigators to choose it for additional study in which the fruits of the methanol crude extract at 1 mg/mL demonstrated 80% elastase and 87% hyaluronidase inhibitory activities. In addition, the investigators isolated 1,2,3,4,6-penta-O-galloyl-beta-D-glucose (PGG), which also exhibited significant inhibition of elastase and hyaluronidase and induction of type II collagen expression. The authors concluded that PGG has the potential as a cutaneous anti-aging agent posing no cytotoxicity concerns and warrants further in vivo study.⁹

A 2010 in vitro study of the anti-aging properties of the extracts of 15 plant species, including T. chebula galls, outgrowths that result from insect bites, was conducted by Manosroi et al. The cold aqueous extract of T. chebula manifested the highest 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical-scavenging activity and highest stimulation index for proliferation of normal human skin fibroblasts. T. chebula, which also inhibited matrix metalloproteinase (MMP)-2 activity, was compared against compounds such as ascorbic acid, alpha-tocopherol, and butylated hydroxytoluene. The investigators concluded that their findings supported the traditional uses of T. chebula gall in Thai medicine and suggest that T. chebula would be beneficial for inclusion in new anti-aging formulations.³

Later that year, Manosroi et al. characterized the biological activities of the phenolic compounds isolated from T. chebula galls, finding that these compounds (gallic acid, punicalagin, isoterchebulin, 1,3,6-tri-O-galloyl-beta-D-glucopyranose, chebulagic acid, and chebulinic acid) exhibited greater radical-scavenging and melanin-inhibitory activity than the reference compounds ascorbic acid, butylated hydroxytoluene, alpha-tocopherol, arbutin, and kojic acid. Although the T. chebula constituents were less effective than the reference compounds in mushroom tyrosinase inhibition and human tumor cytotoxicity assays, the investigators concluded that the antioxidant and depigmenting activity of the constituents of T. chebula accounted for the beneficial profile of the plant that has emerged over time.¹⁰

The next year, Manosroi et al. assessed the cutaneous anti-aging effects of a gel containing niosomes incorporating a semi-purified fraction including gallic acid derived from T. chebula galls or outgrowths. Human volunteers were enlisted to test skin elasticity and roughness and rabbit skin was used to evaluate skin irritation. The gel containing the semi-purified fractions loaded in niosomes was compared with an unloaded fraction, revealing that the loaded niosomes yielded greater gallic acid chemical stability as well as in vivo anti-aging effects.¹¹ Earlier that year, the team had shown the viability of niosomes, particularly elastic ones, to promote chemical stability for the transdermal absorption of gallic acid in semipurified T. chebula gall fractions in rats. Their findings, they concluded, point to the potential for achieving topical anti-aging benefits from such formulations.¹²

yogesh_more/ Thinkstock.com

In 2012, Akhtar et al. developed a water-in-oil T. chebula formulation and assessed its effects on various parameters. The investigators prepared a base with no active ingredients and a 5% T. chebula formulation, which remained stable at various storage conditions. For 8 weeks, they applied the base as well as the formulation to the cheeks of human volunteers, with weekly evaluations indicating that the formulation as opposed to the base yielded significant improvement, irrespective of time elapsed, in skin moisture content and erythema. The authors concluded that their T. chebula topical cream was effective in rejuvenating human skin.¹³

Wound healing

In 2002, Suguna et al. investigated in vivo the effects of a topically administered alcohol extract of the leaves of T. chebula on the healing of rat dermal wounds. The researchers found that treatment with T. chebula accelerated wound healing, with improved contraction rates and shorter epithelialization periods. T. chebula treatment yielded a 40% increase in the tensile strength of tissues from treated wounds. The authors concluded that T. chebula is beneficial in speeding the wound healing process.²

Immature T. chebula fruit extracts high in tannins are thought to be effective in enhancing the wound healing process, according to Li et al., who found in 2011 that the extracts promoted wound healing in rats, likely due to the antibacterial and angiogenic potency of its tannins.¹

In a 2014 study on wound healing, Singh et al. observed in vitro that T. chebula extracts effectively scavenged free radicals in a DPPH assay and enhanced proliferation of keratinocytes and fibroblasts. They concluded that T. chebula can be considered for use as a bioactive approach to wound healing for its effects in promoting cellular proliferation and inhibiting production of free radicals.⁷

Other biologic activities

A 1995 study by Kurokawa et al. showed that T. chebula was one of four herbal extracts among 10 tested to exhibit a discrete anti–herpes simplex virus type 1 (HSV-1) activity in vitro when combined with acyclovir. Oral administration of the herbs with acyclovir in mice in doses corresponding to human use significantly limited skin lesion development and/or extended mean survival time of infected mice in comparison to any of the herbs or acyclovir used alone.¹⁴

Nam et al. used a 2,4-dinitrofluorobenzene (DNFB)-induced mouse model of atopic symptoms in 2011 and found that a T. chebula seed extract attenuated atopic dermatitis symptoms, resulting in a 52% decrease in the immune response and lower eosinophil levels in nearby skin tissue.⁶

In 2013, Manosroi et al. found that various tannins and one oleanane-type triterpene acid isolated from T. chebula galls displayed strong inhibitory capacity against melanogenesis in mice, with one of the tannins (isoterchebulin) shown to decrease protein levels of tyrosinase, microphthalmia-associated transcription factor, and tyrosine-related protein 1 in mainly a concentration-dependent fashion. Another tannin and several triterpenoids were noted for suppressing 12-O-tetradecanoylphorbol 13-acetate (TPA)-induced inflammation. In addition, constituent phenols manifested strong radical-scavenging activity. In a two-stage carcinogenesis mouse model, the investigators observed that the triterpene acid arjungenin hindered skin tumor promotion after initiation with 7,12-dimethylbenz[a]anthracene (DMBA) and promotion by TPA. Their findings indicate a wide range of biologic activity and potential health benefits associated with T. chebula.¹⁵

In a mouse study in 2014, Singh et al. determined that a new antifungal agent, an apigenin ointment containing extract of T. chebula stem, was effective in significantly reducing the fungal burden from the experimentally-induced dermatophyte Trichopython mentagrophytes. They suggested that this agent warrants consideration in clinically treating dermatophytosis in humans.¹⁶

Triphala, a traditional combination formulation

Long used in Ayurveda, triphala (the word is derived from the Sanskrit tri, three, and phala, fruits) is an antioxidant-rich herbal formulation that combines the dried fruits of T. chebula, Terminalia bellirica, and Emblica officinalis. Naik et al. observed, in a 2005 in vitro study of the aqueous extract of the fruits of T. chebula, T. bellirica, and E. officinalis, as well as their equiproportional mixture triphala, that T. chebula was the most effective at scavenging free radicals. They noted that triphala appears to synergistically combine the strengths of each of its primary components.¹⁷ Subsequent studies have demonstrated that triphala is a strong source of natural antioxidants and exhibits a wide range of beneficial activities, including free radical scavenging, antioxidant, anti-inflammatory, analgesic, antibacterial, antimutagenic, wound healing, antistress, adaptogenic, hypoglycemic, anticancer, chemoprotective, radioprotective, chemopreventive, and wound healing.^5,18-21

Extracts of T. chebula also have been combined with those of E. officinalis, T. bellirica, Albizia lebbeck, Piper nigrum, Zingiber officinale, and Piper longum in a polyherbal formulation (Aller-7/NR-A2) that has been found safe for the treatment of allergic rhinitis.²²

Conclusion

The use of T. chebula in various traditional medical practices around the world is well established. There is ample evidence supporting multiple biologic properties of this Ayurvedic staple. While it is not a standard ingredient in dermatologic health care in the West, the data support continued research as to how best to incorporate this agent.

References

1. BMC Complement Altern Med. 2011 Oct 7;11:86.

2. Phytother Res. 2002 May;16(3):227-31.

3. Pharm Biol. 2010 Apr;48(4):469-81.

4. Pak J Biol Sci. 2007 Jul 1;10(13):2241-56.

5. BMC Complement Altern Med. 2010 May 13;10:20.

6. Int J Mol Med. 2011 Dec;28(6):1013-8.

7. Evid Based Complement Alternat Med. 2014;2014:701656.

8. Phytother Res. 2004 Sep;18:737-41.

9. Acta Pol Pharm. 2010 Mar-Apr;67(2):145-50.

10. Nat Prod Res. 2010 Dec;24(20):1915-26.

11. Pharm Biol. 2011 Nov;49(11):1190-203.

12. Pharm Biol. 2011 Jun;49(6):553-62.

13. Forsch Komplementmed. 2012;19(1):20-5.

14. Antiviral Res. 1995 May;27(1-2):19-37.

15. Chem Biodivers. 2013 Aug;10(8):1448-63.

16. Mycoses. 2014 Aug;57(8):497-506.

17. Phytother Res. 2005 Jul;19(7):582-6.

18. Chin J Integr Med. 2012 Dec;18(12):946-54.

19. J Surg Res. 2008 Jan;144(1):94-101.

20. J Surg Res. 2010 Jan;158(1):162-70.

21. J Altern Complement Med. 2010 Dec;16(12):1301-8.

22. Toxicol Mech Methods. 2005;15(3):193-204.

Dr. Baumann is chief executive officer of the Baumann Cosmetic & Research Institute in the Design District in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann wrote the textbook, “Cosmetic Dermatology: Principles and Practice” (New York: McGraw-Hill, 2002), and a book for consumers, “The Skin Type Solution” (New York: Bantam Dell, 2006). She has contributed to the Cosmeceutical Critique column in Dermatology News since January 2001. Her latest book, “Cosmeceuticals and Cosmetic Ingredients,” was published in November 2014. Dr. Baumann has received funding for clinical grants from Allergan, Aveeno, Avon Products, Evolus, Galderma, GlaxoSmithKline, Kythera Biopharmaceuticals, Mary Kay, Medicis Pharmaceuticals, Neutrogena, Philosophy, Topix Pharmaceuticals, and Unilever.

Terminalia chebula, a member of the Combretaceae family, is an evergreen plant found abundantly in India, Pakistan, China, Thailand, Sri Lanka, and Malaysia.^1,2 It has long been used in traditional medicine, particularly Ayurveda, as well as in Thai traditional medicine.³ It also has also been used for many years in the traditional medicine of the Samahni valley of Pakistan to treat chronic ulcers as well as dental caries and heart ailments.⁴ Other traditional indications include asthma and urinary disorders.⁵ In Thailand, it has been used to treat skin diseases and to promote wound healing and rejuvenation.¹ It is particularly known for its potent antioxidant and antimicrobial properties.⁶ The wide array of health benefits associated with T. chebula is attributed to its high content of phenolic compounds, flavonol glycosides, and other phytonutrients.⁷

Antioxidant, anti-aging, and depigmenting effects

In 2004, Na et al. observed that T. chebula fruit extract exerted an inhibitory effect on the age-dependent shortening of telomeres and UVB-induced oxidative damage in vitro.⁸

Kim et al. screened 50 Korean plants to identify natural sources of elastase and hyaluronidase inhibitors in 2010. The strong efficacy of T. chebula led the investigators to choose it for additional study in which the fruits of the methanol crude extract at 1 mg/mL demonstrated 80% elastase and 87% hyaluronidase inhibitory activities. In addition, the investigators isolated 1,2,3,4,6-penta-O-galloyl-beta-D-glucose (PGG), which also exhibited significant inhibition of elastase and hyaluronidase and induction of type II collagen expression. The authors concluded that PGG has the potential as a cutaneous anti-aging agent posing no cytotoxicity concerns and warrants further in vivo study.⁹

A 2010 in vitro study of the anti-aging properties of the extracts of 15 plant species, including T. chebula galls, outgrowths that result from insect bites, was conducted by Manosroi et al. The cold aqueous extract of T. chebula manifested the highest 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical-scavenging activity and highest stimulation index for proliferation of normal human skin fibroblasts. T. chebula, which also inhibited matrix metalloproteinase (MMP)-2 activity, was compared against compounds such as ascorbic acid, alpha-tocopherol, and butylated hydroxytoluene. The investigators concluded that their findings supported the traditional uses of T. chebula gall in Thai medicine and suggest that T. chebula would be beneficial for inclusion in new anti-aging formulations.³

Later that year, Manosroi et al. characterized the biological activities of the phenolic compounds isolated from T. chebula galls, finding that these compounds (gallic acid, punicalagin, isoterchebulin, 1,3,6-tri-O-galloyl-beta-D-glucopyranose, chebulagic acid, and chebulinic acid) exhibited greater radical-scavenging and melanin-inhibitory activity than the reference compounds ascorbic acid, butylated hydroxytoluene, alpha-tocopherol, arbutin, and kojic acid. Although the T. chebula constituents were less effective than the reference compounds in mushroom tyrosinase inhibition and human tumor cytotoxicity assays, the investigators concluded that the antioxidant and depigmenting activity of the constituents of T. chebula accounted for the beneficial profile of the plant that has emerged over time.¹⁰

The next year, Manosroi et al. assessed the cutaneous anti-aging effects of a gel containing niosomes incorporating a semi-purified fraction including gallic acid derived from T. chebula galls or outgrowths. Human volunteers were enlisted to test skin elasticity and roughness and rabbit skin was used to evaluate skin irritation. The gel containing the semi-purified fractions loaded in niosomes was compared with an unloaded fraction, revealing that the loaded niosomes yielded greater gallic acid chemical stability as well as in vivo anti-aging effects.¹¹ Earlier that year, the team had shown the viability of niosomes, particularly elastic ones, to promote chemical stability for the transdermal absorption of gallic acid in semipurified T. chebula gall fractions in rats. Their findings, they concluded, point to the potential for achieving topical anti-aging benefits from such formulations.¹²

yogesh_more/ Thinkstock.com

In 2012, Akhtar et al. developed a water-in-oil T. chebula formulation and assessed its effects on various parameters. The investigators prepared a base with no active ingredients and a 5% T. chebula formulation, which remained stable at various storage conditions. For 8 weeks, they applied the base as well as the formulation to the cheeks of human volunteers, with weekly evaluations indicating that the formulation as opposed to the base yielded significant improvement, irrespective of time elapsed, in skin moisture content and erythema. The authors concluded that their T. chebula topical cream was effective in rejuvenating human skin.¹³

Wound healing

In 2002, Suguna et al. investigated in vivo the effects of a topically administered alcohol extract of the leaves of T. chebula on the healing of rat dermal wounds. The researchers found that treatment with T. chebula accelerated wound healing, with improved contraction rates and shorter epithelialization periods. T. chebula treatment yielded a 40% increase in the tensile strength of tissues from treated wounds. The authors concluded that T. chebula is beneficial in speeding the wound healing process.²

Immature T. chebula fruit extracts high in tannins are thought to be effective in enhancing the wound healing process, according to Li et al., who found in 2011 that the extracts promoted wound healing in rats, likely due to the antibacterial and angiogenic potency of its tannins.¹

In a 2014 study on wound healing, Singh et al. observed in vitro that T. chebula extracts effectively scavenged free radicals in a DPPH assay and enhanced proliferation of keratinocytes and fibroblasts. They concluded that T. chebula can be considered for use as a bioactive approach to wound healing for its effects in promoting cellular proliferation and inhibiting production of free radicals.⁷

Other biologic activities

A 1995 study by Kurokawa et al. showed that T. chebula was one of four herbal extracts among 10 tested to exhibit a discrete anti–herpes simplex virus type 1 (HSV-1) activity in vitro when combined with acyclovir. Oral administration of the herbs with acyclovir in mice in doses corresponding to human use significantly limited skin lesion development and/or extended mean survival time of infected mice in comparison to any of the herbs or acyclovir used alone.¹⁴

Nam et al. used a 2,4-dinitrofluorobenzene (DNFB)-induced mouse model of atopic symptoms in 2011 and found that a T. chebula seed extract attenuated atopic dermatitis symptoms, resulting in a 52% decrease in the immune response and lower eosinophil levels in nearby skin tissue.⁶

In 2013, Manosroi et al. found that various tannins and one oleanane-type triterpene acid isolated from T. chebula galls displayed strong inhibitory capacity against melanogenesis in mice, with one of the tannins (isoterchebulin) shown to decrease protein levels of tyrosinase, microphthalmia-associated transcription factor, and tyrosine-related protein 1 in mainly a concentration-dependent fashion. Another tannin and several triterpenoids were noted for suppressing 12-O-tetradecanoylphorbol 13-acetate (TPA)-induced inflammation. In addition, constituent phenols manifested strong radical-scavenging activity. In a two-stage carcinogenesis mouse model, the investigators observed that the triterpene acid arjungenin hindered skin tumor promotion after initiation with 7,12-dimethylbenz[a]anthracene (DMBA) and promotion by TPA. Their findings indicate a wide range of biologic activity and potential health benefits associated with T. chebula.¹⁵

In a mouse study in 2014, Singh et al. determined that a new antifungal agent, an apigenin ointment containing extract of T. chebula stem, was effective in significantly reducing the fungal burden from the experimentally-induced dermatophyte Trichopython mentagrophytes. They suggested that this agent warrants consideration in clinically treating dermatophytosis in humans.¹⁶

Triphala, a traditional combination formulation

Long used in Ayurveda, triphala (the word is derived from the Sanskrit tri, three, and phala, fruits) is an antioxidant-rich herbal formulation that combines the dried fruits of T. chebula, Terminalia bellirica, and Emblica officinalis. Naik et al. observed, in a 2005 in vitro study of the aqueous extract of the fruits of T. chebula, T. bellirica, and E. officinalis, as well as their equiproportional mixture triphala, that T. chebula was the most effective at scavenging free radicals. They noted that triphala appears to synergistically combine the strengths of each of its primary components.¹⁷ Subsequent studies have demonstrated that triphala is a strong source of natural antioxidants and exhibits a wide range of beneficial activities, including free radical scavenging, antioxidant, anti-inflammatory, analgesic, antibacterial, antimutagenic, wound healing, antistress, adaptogenic, hypoglycemic, anticancer, chemoprotective, radioprotective, chemopreventive, and wound healing.^5,18-21

Extracts of T. chebula also have been combined with those of E. officinalis, T. bellirica, Albizia lebbeck, Piper nigrum, Zingiber officinale, and Piper longum in a polyherbal formulation (Aller-7/NR-A2) that has been found safe for the treatment of allergic rhinitis.²²

Conclusion

The use of T. chebula in various traditional medical practices around the world is well established. There is ample evidence supporting multiple biologic properties of this Ayurvedic staple. While it is not a standard ingredient in dermatologic health care in the West, the data support continued research as to how best to incorporate this agent.

References

1. BMC Complement Altern Med. 2011 Oct 7;11:86.

2. Phytother Res. 2002 May;16(3):227-31.

3. Pharm Biol. 2010 Apr;48(4):469-81.

4. Pak J Biol Sci. 2007 Jul 1;10(13):2241-56.

5. BMC Complement Altern Med. 2010 May 13;10:20.

6. Int J Mol Med. 2011 Dec;28(6):1013-8.

7. Evid Based Complement Alternat Med. 2014;2014:701656.

8. Phytother Res. 2004 Sep;18:737-41.

9. Acta Pol Pharm. 2010 Mar-Apr;67(2):145-50.

10. Nat Prod Res. 2010 Dec;24(20):1915-26.

11. Pharm Biol. 2011 Nov;49(11):1190-203.

12. Pharm Biol. 2011 Jun;49(6):553-62.

13. Forsch Komplementmed. 2012;19(1):20-5.

14. Antiviral Res. 1995 May;27(1-2):19-37.

15. Chem Biodivers. 2013 Aug;10(8):1448-63.

16. Mycoses. 2014 Aug;57(8):497-506.

17. Phytother Res. 2005 Jul;19(7):582-6.

18. Chin J Integr Med. 2012 Dec;18(12):946-54.

19. J Surg Res. 2008 Jan;144(1):94-101.

20. J Surg Res. 2010 Jan;158(1):162-70.

21. J Altern Complement Med. 2010 Dec;16(12):1301-8.

22. Toxicol Mech Methods. 2005;15(3):193-204.

Dr. Baumann is chief executive officer of the Baumann Cosmetic & Research Institute in the Design District in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann wrote the textbook, “Cosmetic Dermatology: Principles and Practice” (New York: McGraw-Hill, 2002), and a book for consumers, “The Skin Type Solution” (New York: Bantam Dell, 2006). She has contributed to the Cosmeceutical Critique column in Dermatology News since January 2001. Her latest book, “Cosmeceuticals and Cosmetic Ingredients,” was published in November 2014. Dr. Baumann has received funding for clinical grants from Allergan, Aveeno, Avon Products, Evolus, Galderma, GlaxoSmithKline, Kythera Biopharmaceuticals, Mary Kay, Medicis Pharmaceuticals, Neutrogena, Philosophy, Topix Pharmaceuticals, and Unilever.

Used for centuries by humans for its health-promoting qualities, royal jelly is a yellowish, viscous secretion from the hypopharyngeal and mandibular glands of worker bees that nourishes bee larvae of all kinds (i.e., drones, workers, queens) after which it becomes the exclusive nourishment for queens throughout their development.^1-3 A wide range of biologic activity has been attributed to royal jelly, including antitumor, antibacterial, anti-inflammatory, antioxidant, collagen production-promoting, immunomodulatory, and wound healing.^3-8 Royal jelly is used in cosmetics, health tonics (particularly in Asia), dietary supplements, and beverages.^2,9

Produced from pollen, royal jelly contains water, proteins (82%-90% of which are known as the major royal jelly proteins, with five primary members), lipids – including its primary unsaturated fatty acid, 10-hydroxy-2-decenoic acid (10-HDA) – sugars, carbohydrates, free amino acids, vitamins, and minerals.^4,7,10 Many of the benefits to human health linked to royal jelly can be partly attributed to the activity of its lipids, particularly 10-HDA, which render the royal jelly emulsion highly acidic and impart antimicrobial properties.¹⁰ These and other constituents of royal jelly operate in ways that are thought to yield broad protection against skin aging and cancer development, modulation of the immune system, induction of neurogenesis, and alleviation of menopausal symptoms.¹ This column will focus on recent studies pertaining to the topical use of royal jelly.

Wound healing

In 2008, Abdelatif et al. conducted a pilot study to determine the safety and effectiveness of a then-new ointment combining royal jelly and panthenol (Pedyphar) in 60 patients with limb-threatening diabetic foot infections. After 9 weeks of treatment and through 6 months of follow-up, 96% of subjects with full-thickness skin ulcers (Wagner grades 1 and 2) or deep tissue infection and suspected osteomyelitis (grade 3) responded well, with all grade 1 and 2 ulcers healing and 92% of grade 3 ulcers healing. All patients with gangrenous lesions (grades 4 and 5) healed after surgical excision, debridement, and conservative treatment with the royal jelly/panthenol product. The researchers called for more double-blind, randomized controlled studies to confirm their promising findings of the safety and efficacy of the royal jelly/panthenol combination.¹¹

Two years later, Kim et al. treated freshly scratched normal human dermal fibroblasts with different concentrations of royal jelly (0.1 mg/mL, 1.0 mg/mL, or 5 mg/mL) for up to 48 hours. Fibroblast migration was found to have peaked at 24 hours after wound induction, with royal jelly significantly and dose-dependently accelerating the migration at the 8-hour mark. Royal jelly also influenced several fibroblast lipids involved in the wound healing process, with a decrease in cholesterol level and an increase in sphinganines.¹²

A small study with eight subjects was done in 2011 by Siavash et al. to evaluate the efficacy of topically applied royal jelly for diabetic foot ulcers. Seven of the eight ulcers treated healed, with a mean healing time of 41 days. The eighth ulcer improved, diminishing significantly in size. The researchers concluded that a royal jelly dressing is an effective alternative for treatment of diabetic foot ulcers.¹³ However, the same team conducted a double-blind, placebo-controlled clinical trial of topical royal jelly on diabetic foot ulcers in 25 patients (6 females, 19 males) and found no significant differences between 5% sterile topical royal jelly or placebo.⁶

Collagen production

shootthebreeze/thinkstockphotos.com

A decade ago, Koya-Miyata et al. showed that royal jelly promotes collagen synthesis by skin fibroblasts in the presence of ascorbic acid-2-O-alpha-glucoside. They also showed that its primary fatty acid constituent, 10-HDA, facilitates the collagen production by fibroblasts treated with ascorbic acid-2-O-alpha-glucoside through activation of transforming growth factor-beta 1 production.₅

Photoprotection

Park et al. measured the 10-HDA content of royal jelly in 2011 and studied its effects on UVB-induced skin photoaging in normal human dermal fibroblasts. The introduction of royal jelly (0.211% 10-HDA) promoted the production of procollagen type I and transforming growth factor (TGF)-beta-1 without affecting matrix metalloproteinase (MMP)-1 levels. The investigators concluded that the impact of royal jelly on collagen production positioned the bee product as a potential photoprotectant against UVB-induced photoaging.¹⁴ The next year, Park et al. observed that the production of type I collagen in the dorsal skin of ovariectomized Sprague-Dawley rats was enhanced by the dietary supplementation of 1% royal jelly extract. Although MMP-1 levels were unaffected, the investigators speculated that the effects on collagen synthesis alone were sufficient for royal jelly to provide anti-aging activity.⁴

In 2013, Zheng et al. found that 10-HDA significantly protected fibroblasts from UVA-induced cytotoxicity, reactive oxygen species, and cellular senescence. They also noted that 10-HDA inhibited the UVA-generated expression of MMP-1 and -3, and stimulated collagen production. Treatment with 10-HDA also reduced the activation of the c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (MAPK) pathways. The researchers concluded that this royal jelly fatty acid appears to be a promising agent for the prevention and treatment of cutaneous photoaging.⁸

Skin whitening

In 2011, Han et al. reported that royal jelly dose-dependently inhibited melanin biosynthesis in the B16F1 mouse melanocyte cell line by reducing tyrosinase activity. Royal jelly also lowered mRNA levels of tyrosinase. The investigators concluded that royal jelly may be a viable option in the skin-lightening arsenal.³

Safety

There are some reports of contact dermatitis from the use of topical royal jelly.¹⁵ Far more significant, while rare, adverse reactions have been linked to oral use of royal jelly, including acute asthma, anaphylaxis, and even death.^2,16,17

Conclusion

Royal jelly is one of several bee products found to have beneficial health effects in humans. Various dermatologic applications of royal jelly have been employed in recent decades. More research is necessary, though, to determine just how useful this bee product may be for a range of cutaneous conditions.

References

1. J Med Food. 2013;16(2):96-102.

2. Biosci Biotechnol Biochem. 2013;77(4):789-95.

3. Am J Chin Med. 2011;39(6):1253-60.

4. J Med Food. 2012;15(6):568-75.

5. Biosci Biotechnol Biochem. 2004 Apr;68(4):767-73.

6. Int Wound J. 2015;12(2):137-42.

7. J Food Sci. 2008 Nov;73(9):R117-24.

8. J Eur Acad Dermatol. Venereol. 2013;27(10):1269-77.

9. Pharmacogn Mag. 2013;9(33):9-13.

10. Ayu. 2012;33(2):178-82.

11. J Wound Care. 2008;17(3):108-10.

12. Nutr Res Pract. 2010;4(5):362-8.

13. J Res Med Sci. 2011;16(7):904-9.

14. J Med Food. 2011;14(9):899-906.

15. Contact Dermatitis. 1983;9(6):452-5.

16. Trop Biomed. 2008;25(3):243-51.

17. J Dermatol. 2011;38(11):1079-81.

Dr. Baumann is chief executive officer of the Baumann Cosmetic & Research Institute in the Design District in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann wrote the textbook, “Cosmetic Dermatology: Principles and Practice” (New York: McGraw-Hill, 2002), and a book for consumers, “The Skin Type Solution” (New York: Bantam Dell, 2006). She has contributed to the Cosmeceutical Critique column in Dermatology News since January 2001. Her latest book, “Cosmeceuticals and Cosmetic Ingredients,” was published in November 2014. Dr. Baumann has received funding for clinical grants from Allergan, Aveeno, Avon Products, Evolus, Galderma, GlaxoSmithKline, Kythera Biopharmaceuticals, Mary Kay, Medicis Pharmaceuticals, Neutrogena, Philosophy, Topix Pharmaceuticals, and Unilever.

Used for centuries by humans for its health-promoting qualities, royal jelly is a yellowish, viscous secretion from the hypopharyngeal and mandibular glands of worker bees that nourishes bee larvae of all kinds (i.e., drones, workers, queens) after which it becomes the exclusive nourishment for queens throughout their development.^1-3 A wide range of biologic activity has been attributed to royal jelly, including antitumor, antibacterial, anti-inflammatory, antioxidant, collagen production-promoting, immunomodulatory, and wound healing.^3-8 Royal jelly is used in cosmetics, health tonics (particularly in Asia), dietary supplements, and beverages.^2,9

Produced from pollen, royal jelly contains water, proteins (82%-90% of which are known as the major royal jelly proteins, with five primary members), lipids – including its primary unsaturated fatty acid, 10-hydroxy-2-decenoic acid (10-HDA) – sugars, carbohydrates, free amino acids, vitamins, and minerals.^4,7,10 Many of the benefits to human health linked to royal jelly can be partly attributed to the activity of its lipids, particularly 10-HDA, which render the royal jelly emulsion highly acidic and impart antimicrobial properties.¹⁰ These and other constituents of royal jelly operate in ways that are thought to yield broad protection against skin aging and cancer development, modulation of the immune system, induction of neurogenesis, and alleviation of menopausal symptoms.¹ This column will focus on recent studies pertaining to the topical use of royal jelly.

Wound healing

In 2008, Abdelatif et al. conducted a pilot study to determine the safety and effectiveness of a then-new ointment combining royal jelly and panthenol (Pedyphar) in 60 patients with limb-threatening diabetic foot infections. After 9 weeks of treatment and through 6 months of follow-up, 96% of subjects with full-thickness skin ulcers (Wagner grades 1 and 2) or deep tissue infection and suspected osteomyelitis (grade 3) responded well, with all grade 1 and 2 ulcers healing and 92% of grade 3 ulcers healing. All patients with gangrenous lesions (grades 4 and 5) healed after surgical excision, debridement, and conservative treatment with the royal jelly/panthenol product. The researchers called for more double-blind, randomized controlled studies to confirm their promising findings of the safety and efficacy of the royal jelly/panthenol combination.¹¹

Two years later, Kim et al. treated freshly scratched normal human dermal fibroblasts with different concentrations of royal jelly (0.1 mg/mL, 1.0 mg/mL, or 5 mg/mL) for up to 48 hours. Fibroblast migration was found to have peaked at 24 hours after wound induction, with royal jelly significantly and dose-dependently accelerating the migration at the 8-hour mark. Royal jelly also influenced several fibroblast lipids involved in the wound healing process, with a decrease in cholesterol level and an increase in sphinganines.¹²

A small study with eight subjects was done in 2011 by Siavash et al. to evaluate the efficacy of topically applied royal jelly for diabetic foot ulcers. Seven of the eight ulcers treated healed, with a mean healing time of 41 days. The eighth ulcer improved, diminishing significantly in size. The researchers concluded that a royal jelly dressing is an effective alternative for treatment of diabetic foot ulcers.¹³ However, the same team conducted a double-blind, placebo-controlled clinical trial of topical royal jelly on diabetic foot ulcers in 25 patients (6 females, 19 males) and found no significant differences between 5% sterile topical royal jelly or placebo.⁶

Collagen production

shootthebreeze/thinkstockphotos.com

A decade ago, Koya-Miyata et al. showed that royal jelly promotes collagen synthesis by skin fibroblasts in the presence of ascorbic acid-2-O-alpha-glucoside. They also showed that its primary fatty acid constituent, 10-HDA, facilitates the collagen production by fibroblasts treated with ascorbic acid-2-O-alpha-glucoside through activation of transforming growth factor-beta 1 production.₅

Photoprotection

Park et al. measured the 10-HDA content of royal jelly in 2011 and studied its effects on UVB-induced skin photoaging in normal human dermal fibroblasts. The introduction of royal jelly (0.211% 10-HDA) promoted the production of procollagen type I and transforming growth factor (TGF)-beta-1 without affecting matrix metalloproteinase (MMP)-1 levels. The investigators concluded that the impact of royal jelly on collagen production positioned the bee product as a potential photoprotectant against UVB-induced photoaging.¹⁴ The next year, Park et al. observed that the production of type I collagen in the dorsal skin of ovariectomized Sprague-Dawley rats was enhanced by the dietary supplementation of 1% royal jelly extract. Although MMP-1 levels were unaffected, the investigators speculated that the effects on collagen synthesis alone were sufficient for royal jelly to provide anti-aging activity.⁴

In 2013, Zheng et al. found that 10-HDA significantly protected fibroblasts from UVA-induced cytotoxicity, reactive oxygen species, and cellular senescence. They also noted that 10-HDA inhibited the UVA-generated expression of MMP-1 and -3, and stimulated collagen production. Treatment with 10-HDA also reduced the activation of the c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (MAPK) pathways. The researchers concluded that this royal jelly fatty acid appears to be a promising agent for the prevention and treatment of cutaneous photoaging.⁸

Skin whitening

In 2011, Han et al. reported that royal jelly dose-dependently inhibited melanin biosynthesis in the B16F1 mouse melanocyte cell line by reducing tyrosinase activity. Royal jelly also lowered mRNA levels of tyrosinase. The investigators concluded that royal jelly may be a viable option in the skin-lightening arsenal.³

Safety

There are some reports of contact dermatitis from the use of topical royal jelly.¹⁵ Far more significant, while rare, adverse reactions have been linked to oral use of royal jelly, including acute asthma, anaphylaxis, and even death.^2,16,17

Conclusion

Royal jelly is one of several bee products found to have beneficial health effects in humans. Various dermatologic applications of royal jelly have been employed in recent decades. More research is necessary, though, to determine just how useful this bee product may be for a range of cutaneous conditions.

References

1. J Med Food. 2013;16(2):96-102.

2. Biosci Biotechnol Biochem. 2013;77(4):789-95.

3. Am J Chin Med. 2011;39(6):1253-60.

4. J Med Food. 2012;15(6):568-75.

5. Biosci Biotechnol Biochem. 2004 Apr;68(4):767-73.

6. Int Wound J. 2015;12(2):137-42.

7. J Food Sci. 2008 Nov;73(9):R117-24.

8. J Eur Acad Dermatol. Venereol. 2013;27(10):1269-77.

9. Pharmacogn Mag. 2013;9(33):9-13.

10. Ayu. 2012;33(2):178-82.

11. J Wound Care. 2008;17(3):108-10.

12. Nutr Res Pract. 2010;4(5):362-8.

13. J Res Med Sci. 2011;16(7):904-9.

14. J Med Food. 2011;14(9):899-906.

15. Contact Dermatitis. 1983;9(6):452-5.

16. Trop Biomed. 2008;25(3):243-51.

17. J Dermatol. 2011;38(11):1079-81.

Dr. Baumann is chief executive officer of the Baumann Cosmetic & Research Institute in the Design District in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann wrote the textbook, “Cosmetic Dermatology: Principles and Practice” (New York: McGraw-Hill, 2002), and a book for consumers, “The Skin Type Solution” (New York: Bantam Dell, 2006). She has contributed to the Cosmeceutical Critique column in Dermatology News since January 2001. Her latest book, “Cosmeceuticals and Cosmetic Ingredients,” was published in November 2014. Dr. Baumann has received funding for clinical grants from Allergan, Aveeno, Avon Products, Evolus, Galderma, GlaxoSmithKline, Kythera Biopharmaceuticals, Mary Kay, Medicis Pharmaceuticals, Neutrogena, Philosophy, Topix Pharmaceuticals, and Unilever.

Used for centuries by humans for its health-promoting qualities, royal jelly is a yellowish, viscous secretion from the hypopharyngeal and mandibular glands of worker bees that nourishes bee larvae of all kinds (i.e., drones, workers, queens) after which it becomes the exclusive nourishment for queens throughout their development.^1-3 A wide range of biologic activity has been attributed to royal jelly, including antitumor, antibacterial, anti-inflammatory, antioxidant, collagen production-promoting, immunomodulatory, and wound healing.^3-8 Royal jelly is used in cosmetics, health tonics (particularly in Asia), dietary supplements, and beverages.^2,9

Produced from pollen, royal jelly contains water, proteins (82%-90% of which are known as the major royal jelly proteins, with five primary members), lipids – including its primary unsaturated fatty acid, 10-hydroxy-2-decenoic acid (10-HDA) – sugars, carbohydrates, free amino acids, vitamins, and minerals.^4,7,10 Many of the benefits to human health linked to royal jelly can be partly attributed to the activity of its lipids, particularly 10-HDA, which render the royal jelly emulsion highly acidic and impart antimicrobial properties.¹⁰ These and other constituents of royal jelly operate in ways that are thought to yield broad protection against skin aging and cancer development, modulation of the immune system, induction of neurogenesis, and alleviation of menopausal symptoms.¹ This column will focus on recent studies pertaining to the topical use of royal jelly.

Wound healing

In 2008, Abdelatif et al. conducted a pilot study to determine the safety and effectiveness of a then-new ointment combining royal jelly and panthenol (Pedyphar) in 60 patients with limb-threatening diabetic foot infections. After 9 weeks of treatment and through 6 months of follow-up, 96% of subjects with full-thickness skin ulcers (Wagner grades 1 and 2) or deep tissue infection and suspected osteomyelitis (grade 3) responded well, with all grade 1 and 2 ulcers healing and 92% of grade 3 ulcers healing. All patients with gangrenous lesions (grades 4 and 5) healed after surgical excision, debridement, and conservative treatment with the royal jelly/panthenol product. The researchers called for more double-blind, randomized controlled studies to confirm their promising findings of the safety and efficacy of the royal jelly/panthenol combination.¹¹

Two years later, Kim et al. treated freshly scratched normal human dermal fibroblasts with different concentrations of royal jelly (0.1 mg/mL, 1.0 mg/mL, or 5 mg/mL) for up to 48 hours. Fibroblast migration was found to have peaked at 24 hours after wound induction, with royal jelly significantly and dose-dependently accelerating the migration at the 8-hour mark. Royal jelly also influenced several fibroblast lipids involved in the wound healing process, with a decrease in cholesterol level and an increase in sphinganines.¹²

A small study with eight subjects was done in 2011 by Siavash et al. to evaluate the efficacy of topically applied royal jelly for diabetic foot ulcers. Seven of the eight ulcers treated healed, with a mean healing time of 41 days. The eighth ulcer improved, diminishing significantly in size. The researchers concluded that a royal jelly dressing is an effective alternative for treatment of diabetic foot ulcers.¹³ However, the same team conducted a double-blind, placebo-controlled clinical trial of topical royal jelly on diabetic foot ulcers in 25 patients (6 females, 19 males) and found no significant differences between 5% sterile topical royal jelly or placebo.⁶

Collagen production

shootthebreeze/thinkstockphotos.com

A decade ago, Koya-Miyata et al. showed that royal jelly promotes collagen synthesis by skin fibroblasts in the presence of ascorbic acid-2-O-alpha-glucoside. They also showed that its primary fatty acid constituent, 10-HDA, facilitates the collagen production by fibroblasts treated with ascorbic acid-2-O-alpha-glucoside through activation of transforming growth factor-beta 1 production.₅

Photoprotection

Park et al. measured the 10-HDA content of royal jelly in 2011 and studied its effects on UVB-induced skin photoaging in normal human dermal fibroblasts. The introduction of royal jelly (0.211% 10-HDA) promoted the production of procollagen type I and transforming growth factor (TGF)-beta-1 without affecting matrix metalloproteinase (MMP)-1 levels. The investigators concluded that the impact of royal jelly on collagen production positioned the bee product as a potential photoprotectant against UVB-induced photoaging.¹⁴ The next year, Park et al. observed that the production of type I collagen in the dorsal skin of ovariectomized Sprague-Dawley rats was enhanced by the dietary supplementation of 1% royal jelly extract. Although MMP-1 levels were unaffected, the investigators speculated that the effects on collagen synthesis alone were sufficient for royal jelly to provide anti-aging activity.⁴

In 2013, Zheng et al. found that 10-HDA significantly protected fibroblasts from UVA-induced cytotoxicity, reactive oxygen species, and cellular senescence. They also noted that 10-HDA inhibited the UVA-generated expression of MMP-1 and -3, and stimulated collagen production. Treatment with 10-HDA also reduced the activation of the c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (MAPK) pathways. The researchers concluded that this royal jelly fatty acid appears to be a promising agent for the prevention and treatment of cutaneous photoaging.⁸

Skin whitening

In 2011, Han et al. reported that royal jelly dose-dependently inhibited melanin biosynthesis in the B16F1 mouse melanocyte cell line by reducing tyrosinase activity. Royal jelly also lowered mRNA levels of tyrosinase. The investigators concluded that royal jelly may be a viable option in the skin-lightening arsenal.³

Safety

There are some reports of contact dermatitis from the use of topical royal jelly.¹⁵ Far more significant, while rare, adverse reactions have been linked to oral use of royal jelly, including acute asthma, anaphylaxis, and even death.^2,16,17

Conclusion

Royal jelly is one of several bee products found to have beneficial health effects in humans. Various dermatologic applications of royal jelly have been employed in recent decades. More research is necessary, though, to determine just how useful this bee product may be for a range of cutaneous conditions.

References

1. J Med Food. 2013;16(2):96-102.

2. Biosci Biotechnol Biochem. 2013;77(4):789-95.

3. Am J Chin Med. 2011;39(6):1253-60.

4. J Med Food. 2012;15(6):568-75.

5. Biosci Biotechnol Biochem. 2004 Apr;68(4):767-73.

6. Int Wound J. 2015;12(2):137-42.

7. J Food Sci. 2008 Nov;73(9):R117-24.

8. J Eur Acad Dermatol. Venereol. 2013;27(10):1269-77.

9. Pharmacogn Mag. 2013;9(33):9-13.

10. Ayu. 2012;33(2):178-82.

11. J Wound Care. 2008;17(3):108-10.

12. Nutr Res Pract. 2010;4(5):362-8.

13. J Res Med Sci. 2011;16(7):904-9.

14. J Med Food. 2011;14(9):899-906.

15. Contact Dermatitis. 1983;9(6):452-5.

16. Trop Biomed. 2008;25(3):243-51.

17. J Dermatol. 2011;38(11):1079-81.

Dr. Baumann is chief executive officer of the Baumann Cosmetic & Research Institute in the Design District in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann wrote the textbook, “Cosmetic Dermatology: Principles and Practice” (New York: McGraw-Hill, 2002), and a book for consumers, “The Skin Type Solution” (New York: Bantam Dell, 2006). She has contributed to the Cosmeceutical Critique column in Dermatology News since January 2001. Her latest book, “Cosmeceuticals and Cosmetic Ingredients,” was published in November 2014. Dr. Baumann has received funding for clinical grants from Allergan, Aveeno, Avon Products, Evolus, Galderma, GlaxoSmithKline, Kythera Biopharmaceuticals, Mary Kay, Medicis Pharmaceuticals, Neutrogena, Philosophy, Topix Pharmaceuticals, and Unilever.

Native to China, India, and Iran, Melia azedarach – also known as Chinaberry (Ku-lian), Pride of China, Indian lilac, Persian lilac, and white cedar – is a large nondeciduous tree now cultivated throughout the world.^1-3 The leaves and fruits of this member of the Meliaceae family have been found to exhibit anthelmintic and antifeedant activity toward insects.⁴ The root bark or dried stem bark of the plant is used in traditional Chinese medicine to treat dermatoses and to expel and repel worms.^5,6M. azedarach has also been used in Ayurveda³; it is known as Bakayn in India and Pakistan, where it has been used in traditional medicine to treat leprosy, scrofula, nausea, vomiting, thirst, and eruptive skin conditions.^3,7

Traditional indications

Cropley and Hasegawa noted in 2007 that M. azedarach was used in the 19th century in the United States primarily as an anthelmintic, but also to treat tinea capitis and to eliminate lice.Further, they noted that the plant, which was widely cultivated in the South, was used, according to the literature of the 1800s, as a diuretic, as well as to promote hair growth, and treat scalp eruptions, fever, and malaria.⁸

A 2006 ethnopharmacologic study by Saikia et al. of medicinal plants used in Assam (Northeast India) to treat skin disorders and for cosmetic purposes revealed that M. azedarach was one of the primary plants used for medicinal purposes, including 18 skin conditions such as acne, burns, carbuncles, abscesses, measles, pediculosis, cellulitis, and prickly heat.⁹

Four years later, in an ethnopharmacologic study of medicinal plants used to treat cutaneous disorders and in folk cosmetics, Abbasi et al. interviewed residents in 30 remote tribal communities in the Northwest Frontier Province of Pakistan, finding that M. azedarach was one of 15 plant species identified as curative for numerous skin diseases, including boils, acne, and scabies.¹⁰

Biologic activity

Various constituents of M. azedarach have been associated with a wide range of biologic activity. The antifungal activity of the plant has been attributed to its hydroxycoumarin content; anti-inflammatory activity to its monoterpenes; bacteriostatic properties to its beta-carboline alkaloids; antiviral effects to its meliacin and meliacarpin; and insecticidal and antifeedant activity to its limonoids, which belong to the tetranortriterpenoid class of compounds.^7,11 Limonoids also are reputed to confer antibacterial, antiviral, and antifungal activities.¹² Recent research suggests the potential of M. azedarach to offer a correspondingly broad impact on various conditions.

Forest & Kim Starr

Anticancer potential

Zhou et al. isolated new ring C-seco limonoids from Brazilian M. azedarach in 2004 and evaluated their cytotoxic activity, finding that two limonoids significantly inhibited HeLa S3 cancer cells.^4,11

In 2009, He et al. extracted water-soluble polysaccharides from the fruit of M. azedarach and assessed their cytotoxic activity against four human cell lines in vitro. They found that the major polysaccharide component exhibited potent cytotoxic activity in the BGC-823 cell line.³ Also that year, Wu et al. isolated three new and multiple known steroids from the leaves of Chinese M. azedarach, finding that two of the newly identified steroids – (20S)-5,24(28)-ergostadiene-3-beta,7-alpha,16-beta,20-tetrol and (20S)-5-ergostene-3-beta,7-alpha,16-beta,20-tetrol – and one of the known ones exerted significant cytotoxic impact in three human cancer cell lines (A-549, H460, U251).¹

Two years later, Wu et al. isolated two new triterpenoids (21,24-cycloeupha-7-ene-3-beta,16beta,21-alpha,25-tetrol and 3-beta-acetoxy-12-beta-hydroxy-eupha-7,24-dien-21,16-beta-olide) and two new steroids (29-hydroperoxy-stigmasta-7,24(28) xi-dien-3-beta-ol and 24-xi-hydroperoxy-24-vinyl-lathosterol) along with several known related substances from M. azedarach bark. Five of the known compounds demonstrated cytotoxic activity against three human cancer cell lines (A-549, H460, HGC27).⁶

More recently, Yuan et al. isolated two limonoids, one triterpenoid, one steroid, and one sesquiterpenoid, as well as nine known limonoids from the bark of M. azedarach. In addition, the investigators observed that seven of the limonoids exhibited significant inhibitory properties against five human tumor cell lines (HL-60, SMM-C7721, A-549, MCF-7, and SW480).⁵

Efficacy against head lice

In 2007, Carpinella et al. investigated in vitro the pediculicidal and ovicidal activity of an M. azedarach extract against Pediculus humanus capitis, noting the increasing resistance of head lice to synthetic drugs. A combination of 20% ripe fruit extract with 10% ripe fruit oil was found to be the most effective in eradicating adult lice (96.5%). The investigators also prepared a formulation of extract and oil at 10% combined with an emulsifier and preservatives that yielded 92.3% mortality of adult lice and complete inhibition of nymph emergence. They concluded that the use of M. azedarach formulations may be a viable and natural way to control head lice.²M. azedarach also has been the key active ingredient in an antimicrobial cream and a preparation to treat tinea pedis.⁷

Topical cream

Saleem et al. reported in 2008 on an herbal cream preparation using a standardized extract of M. azedarach flowers that displayed strong antibacterial activity against cellulitis, pustules, and pyogenic infections, and other conditions in clinical trials in children under the age of 10 years in four different villages in Pakistan. Subjects with bacterial infections anywhere on the body were divided into three groups, one treated with M. azedarach cream, one with placebo (negative control), and one with neomycin (positive control). Each treatment was applied twice daily for 15 days. The investigators observed that the healing effects of M. azedarach were similar to those rendered by neomycin.⁷

Conclusion

Not only has M. azedarach been used in several traditional medical systems, but its uses have consistently included cutaneous indications. Its most convincing modern application may be for head lice, but recent evidence and traditional uses suggest that this versatile plant may indeed warrant a more prominent role in the current dermatologic armamentarium. Future research is needed, and should provide some interesting answers.

References

1. Steroids. 2009 Sep;74(9):761-5.

2. J Am Acad Dermatol. 2007 Feb;56(2):250-6.

3. Fitoterapia. 2009 Oct;80(7):399-403.

4. Chem Pharm Bull (Tokyo). 2005 Oct;53(10):1362-5.

5. Planta Med. 2013 Jan;79(2):163-8.

6. Planta Med. 2011 Jun;77(9):922-8.

7. Phytomedicine. 2008 Apr;15(4):231-6.

8. J Am Acad Dermatol. 2007 Aug;57(2):366-7.

9. J Ethnopharmacol. 2006 Jun 30;106(2):149-57.

10. J Ethnopharmacol. 2010 Mar 24;128(2):322-35.

11. J Nat Prod. 2004 Sep;67(9):1544-7.

12. Chem Biodivers. 2010 Apr;7(4):839-59.

Dr. Baumann is chief executive officer of the Baumann Cosmetic & Research Institute in the Design District in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann wrote the textbook, “Cosmetic Dermatology: Principles and Practice” (New York: McGraw-Hill, 2002), and a book for consumers, “The Skin Type Solution” (New York: Bantam Dell, 2006). She has contributed to the Cosmeceutical Critique column in Dermatology News since January 2001. Her latest book, “Cosmeceuticals and Cosmetic Ingredients,” was published in November 2014. Dr. Baumann has received funding for clinical grants from Allergan, Aveeno, Avon Products, Evolus, Galderma, GlaxoSmithKline, Kythera Biopharmaceuticals, Mary Kay, Medicis Pharmaceuticals, Neutrogena, Philosophy, Topix Pharmaceuticals, and Unilever.

Native to China, India, and Iran, Melia azedarach – also known as Chinaberry (Ku-lian), Pride of China, Indian lilac, Persian lilac, and white cedar – is a large nondeciduous tree now cultivated throughout the world.^1-3 The leaves and fruits of this member of the Meliaceae family have been found to exhibit anthelmintic and antifeedant activity toward insects.⁴ The root bark or dried stem bark of the plant is used in traditional Chinese medicine to treat dermatoses and to expel and repel worms.^5,6M. azedarach has also been used in Ayurveda³; it is known as Bakayn in India and Pakistan, where it has been used in traditional medicine to treat leprosy, scrofula, nausea, vomiting, thirst, and eruptive skin conditions.^3,7

Traditional indications

Cropley and Hasegawa noted in 2007 that M. azedarach was used in the 19th century in the United States primarily as an anthelmintic, but also to treat tinea capitis and to eliminate lice.Further, they noted that the plant, which was widely cultivated in the South, was used, according to the literature of the 1800s, as a diuretic, as well as to promote hair growth, and treat scalp eruptions, fever, and malaria.⁸

A 2006 ethnopharmacologic study by Saikia et al. of medicinal plants used in Assam (Northeast India) to treat skin disorders and for cosmetic purposes revealed that M. azedarach was one of the primary plants used for medicinal purposes, including 18 skin conditions such as acne, burns, carbuncles, abscesses, measles, pediculosis, cellulitis, and prickly heat.⁹

Four years later, in an ethnopharmacologic study of medicinal plants used to treat cutaneous disorders and in folk cosmetics, Abbasi et al. interviewed residents in 30 remote tribal communities in the Northwest Frontier Province of Pakistan, finding that M. azedarach was one of 15 plant species identified as curative for numerous skin diseases, including boils, acne, and scabies.¹⁰

Biologic activity

Various constituents of M. azedarach have been associated with a wide range of biologic activity. The antifungal activity of the plant has been attributed to its hydroxycoumarin content; anti-inflammatory activity to its monoterpenes; bacteriostatic properties to its beta-carboline alkaloids; antiviral effects to its meliacin and meliacarpin; and insecticidal and antifeedant activity to its limonoids, which belong to the tetranortriterpenoid class of compounds.^7,11 Limonoids also are reputed to confer antibacterial, antiviral, and antifungal activities.¹² Recent research suggests the potential of M. azedarach to offer a correspondingly broad impact on various conditions.

Forest & Kim Starr

Anticancer potential

Zhou et al. isolated new ring C-seco limonoids from Brazilian M. azedarach in 2004 and evaluated their cytotoxic activity, finding that two limonoids significantly inhibited HeLa S3 cancer cells.^4,11

In 2009, He et al. extracted water-soluble polysaccharides from the fruit of M. azedarach and assessed their cytotoxic activity against four human cell lines in vitro. They found that the major polysaccharide component exhibited potent cytotoxic activity in the BGC-823 cell line.³ Also that year, Wu et al. isolated three new and multiple known steroids from the leaves of Chinese M. azedarach, finding that two of the newly identified steroids – (20S)-5,24(28)-ergostadiene-3-beta,7-alpha,16-beta,20-tetrol and (20S)-5-ergostene-3-beta,7-alpha,16-beta,20-tetrol – and one of the known ones exerted significant cytotoxic impact in three human cancer cell lines (A-549, H460, U251).¹

Two years later, Wu et al. isolated two new triterpenoids (21,24-cycloeupha-7-ene-3-beta,16beta,21-alpha,25-tetrol and 3-beta-acetoxy-12-beta-hydroxy-eupha-7,24-dien-21,16-beta-olide) and two new steroids (29-hydroperoxy-stigmasta-7,24(28) xi-dien-3-beta-ol and 24-xi-hydroperoxy-24-vinyl-lathosterol) along with several known related substances from M. azedarach bark. Five of the known compounds demonstrated cytotoxic activity against three human cancer cell lines (A-549, H460, HGC27).⁶

More recently, Yuan et al. isolated two limonoids, one triterpenoid, one steroid, and one sesquiterpenoid, as well as nine known limonoids from the bark of M. azedarach. In addition, the investigators observed that seven of the limonoids exhibited significant inhibitory properties against five human tumor cell lines (HL-60, SMM-C7721, A-549, MCF-7, and SW480).⁵

Efficacy against head lice

In 2007, Carpinella et al. investigated in vitro the pediculicidal and ovicidal activity of an M. azedarach extract against Pediculus humanus capitis, noting the increasing resistance of head lice to synthetic drugs. A combination of 20% ripe fruit extract with 10% ripe fruit oil was found to be the most effective in eradicating adult lice (96.5%). The investigators also prepared a formulation of extract and oil at 10% combined with an emulsifier and preservatives that yielded 92.3% mortality of adult lice and complete inhibition of nymph emergence. They concluded that the use of M. azedarach formulations may be a viable and natural way to control head lice.²M. azedarach also has been the key active ingredient in an antimicrobial cream and a preparation to treat tinea pedis.⁷

Topical cream

Saleem et al. reported in 2008 on an herbal cream preparation using a standardized extract of M. azedarach flowers that displayed strong antibacterial activity against cellulitis, pustules, and pyogenic infections, and other conditions in clinical trials in children under the age of 10 years in four different villages in Pakistan. Subjects with bacterial infections anywhere on the body were divided into three groups, one treated with M. azedarach cream, one with placebo (negative control), and one with neomycin (positive control). Each treatment was applied twice daily for 15 days. The investigators observed that the healing effects of M. azedarach were similar to those rendered by neomycin.⁷

Conclusion

Not only has M. azedarach been used in several traditional medical systems, but its uses have consistently included cutaneous indications. Its most convincing modern application may be for head lice, but recent evidence and traditional uses suggest that this versatile plant may indeed warrant a more prominent role in the current dermatologic armamentarium. Future research is needed, and should provide some interesting answers.

References

1. Steroids. 2009 Sep;74(9):761-5.

2. J Am Acad Dermatol. 2007 Feb;56(2):250-6.

3. Fitoterapia. 2009 Oct;80(7):399-403.

4. Chem Pharm Bull (Tokyo). 2005 Oct;53(10):1362-5.

5. Planta Med. 2013 Jan;79(2):163-8.

6. Planta Med. 2011 Jun;77(9):922-8.

7. Phytomedicine. 2008 Apr;15(4):231-6.

8. J Am Acad Dermatol. 2007 Aug;57(2):366-7.

9. J Ethnopharmacol. 2006 Jun 30;106(2):149-57.

10. J Ethnopharmacol. 2010 Mar 24;128(2):322-35.

11. J Nat Prod. 2004 Sep;67(9):1544-7.

12. Chem Biodivers. 2010 Apr;7(4):839-59.

Dr. Baumann is chief executive officer of the Baumann Cosmetic & Research Institute in the Design District in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann wrote the textbook, “Cosmetic Dermatology: Principles and Practice” (New York: McGraw-Hill, 2002), and a book for consumers, “The Skin Type Solution” (New York: Bantam Dell, 2006). She has contributed to the Cosmeceutical Critique column in Dermatology News since January 2001. Her latest book, “Cosmeceuticals and Cosmetic Ingredients,” was published in November 2014. Dr. Baumann has received funding for clinical grants from Allergan, Aveeno, Avon Products, Evolus, Galderma, GlaxoSmithKline, Kythera Biopharmaceuticals, Mary Kay, Medicis Pharmaceuticals, Neutrogena, Philosophy, Topix Pharmaceuticals, and Unilever.

Native to China, India, and Iran, Melia azedarach – also known as Chinaberry (Ku-lian), Pride of China, Indian lilac, Persian lilac, and white cedar – is a large nondeciduous tree now cultivated throughout the world.^1-3 The leaves and fruits of this member of the Meliaceae family have been found to exhibit anthelmintic and antifeedant activity toward insects.⁴ The root bark or dried stem bark of the plant is used in traditional Chinese medicine to treat dermatoses and to expel and repel worms.^5,6M. azedarach has also been used in Ayurveda³; it is known as Bakayn in India and Pakistan, where it has been used in traditional medicine to treat leprosy, scrofula, nausea, vomiting, thirst, and eruptive skin conditions.^3,7

Traditional indications

Cropley and Hasegawa noted in 2007 that M. azedarach was used in the 19th century in the United States primarily as an anthelmintic, but also to treat tinea capitis and to eliminate lice.Further, they noted that the plant, which was widely cultivated in the South, was used, according to the literature of the 1800s, as a diuretic, as well as to promote hair growth, and treat scalp eruptions, fever, and malaria.⁸

A 2006 ethnopharmacologic study by Saikia et al. of medicinal plants used in Assam (Northeast India) to treat skin disorders and for cosmetic purposes revealed that M. azedarach was one of the primary plants used for medicinal purposes, including 18 skin conditions such as acne, burns, carbuncles, abscesses, measles, pediculosis, cellulitis, and prickly heat.⁹

Four years later, in an ethnopharmacologic study of medicinal plants used to treat cutaneous disorders and in folk cosmetics, Abbasi et al. interviewed residents in 30 remote tribal communities in the Northwest Frontier Province of Pakistan, finding that M. azedarach was one of 15 plant species identified as curative for numerous skin diseases, including boils, acne, and scabies.¹⁰

Biologic activity

Various constituents of M. azedarach have been associated with a wide range of biologic activity. The antifungal activity of the plant has been attributed to its hydroxycoumarin content; anti-inflammatory activity to its monoterpenes; bacteriostatic properties to its beta-carboline alkaloids; antiviral effects to its meliacin and meliacarpin; and insecticidal and antifeedant activity to its limonoids, which belong to the tetranortriterpenoid class of compounds.^7,11 Limonoids also are reputed to confer antibacterial, antiviral, and antifungal activities.¹² Recent research suggests the potential of M. azedarach to offer a correspondingly broad impact on various conditions.

Forest & Kim Starr

Anticancer potential

Zhou et al. isolated new ring C-seco limonoids from Brazilian M. azedarach in 2004 and evaluated their cytotoxic activity, finding that two limonoids significantly inhibited HeLa S3 cancer cells.^4,11

In 2009, He et al. extracted water-soluble polysaccharides from the fruit of M. azedarach and assessed their cytotoxic activity against four human cell lines in vitro. They found that the major polysaccharide component exhibited potent cytotoxic activity in the BGC-823 cell line.³ Also that year, Wu et al. isolated three new and multiple known steroids from the leaves of Chinese M. azedarach, finding that two of the newly identified steroids – (20S)-5,24(28)-ergostadiene-3-beta,7-alpha,16-beta,20-tetrol and (20S)-5-ergostene-3-beta,7-alpha,16-beta,20-tetrol – and one of the known ones exerted significant cytotoxic impact in three human cancer cell lines (A-549, H460, U251).¹

Two years later, Wu et al. isolated two new triterpenoids (21,24-cycloeupha-7-ene-3-beta,16beta,21-alpha,25-tetrol and 3-beta-acetoxy-12-beta-hydroxy-eupha-7,24-dien-21,16-beta-olide) and two new steroids (29-hydroperoxy-stigmasta-7,24(28) xi-dien-3-beta-ol and 24-xi-hydroperoxy-24-vinyl-lathosterol) along with several known related substances from M. azedarach bark. Five of the known compounds demonstrated cytotoxic activity against three human cancer cell lines (A-549, H460, HGC27).⁶

More recently, Yuan et al. isolated two limonoids, one triterpenoid, one steroid, and one sesquiterpenoid, as well as nine known limonoids from the bark of M. azedarach. In addition, the investigators observed that seven of the limonoids exhibited significant inhibitory properties against five human tumor cell lines (HL-60, SMM-C7721, A-549, MCF-7, and SW480).⁵

Efficacy against head lice

In 2007, Carpinella et al. investigated in vitro the pediculicidal and ovicidal activity of an M. azedarach extract against Pediculus humanus capitis, noting the increasing resistance of head lice to synthetic drugs. A combination of 20% ripe fruit extract with 10% ripe fruit oil was found to be the most effective in eradicating adult lice (96.5%). The investigators also prepared a formulation of extract and oil at 10% combined with an emulsifier and preservatives that yielded 92.3% mortality of adult lice and complete inhibition of nymph emergence. They concluded that the use of M. azedarach formulations may be a viable and natural way to control head lice.²M. azedarach also has been the key active ingredient in an antimicrobial cream and a preparation to treat tinea pedis.⁷

Topical cream

Saleem et al. reported in 2008 on an herbal cream preparation using a standardized extract of M. azedarach flowers that displayed strong antibacterial activity against cellulitis, pustules, and pyogenic infections, and other conditions in clinical trials in children under the age of 10 years in four different villages in Pakistan. Subjects with bacterial infections anywhere on the body were divided into three groups, one treated with M. azedarach cream, one with placebo (negative control), and one with neomycin (positive control). Each treatment was applied twice daily for 15 days. The investigators observed that the healing effects of M. azedarach were similar to those rendered by neomycin.⁷

Conclusion

Not only has M. azedarach been used in several traditional medical systems, but its uses have consistently included cutaneous indications. Its most convincing modern application may be for head lice, but recent evidence and traditional uses suggest that this versatile plant may indeed warrant a more prominent role in the current dermatologic armamentarium. Future research is needed, and should provide some interesting answers.

References

1. Steroids. 2009 Sep;74(9):761-5.

2. J Am Acad Dermatol. 2007 Feb;56(2):250-6.

3. Fitoterapia. 2009 Oct;80(7):399-403.

4. Chem Pharm Bull (Tokyo). 2005 Oct;53(10):1362-5.

5. Planta Med. 2013 Jan;79(2):163-8.

6. Planta Med. 2011 Jun;77(9):922-8.

7. Phytomedicine. 2008 Apr;15(4):231-6.

8. J Am Acad Dermatol. 2007 Aug;57(2):366-7.

9. J Ethnopharmacol. 2006 Jun 30;106(2):149-57.

10. J Ethnopharmacol. 2010 Mar 24;128(2):322-35.

11. J Nat Prod. 2004 Sep;67(9):1544-7.

12. Chem Biodivers. 2010 Apr;7(4):839-59.

Dr. Baumann is chief executive officer of the Baumann Cosmetic & Research Institute in the Design District in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann wrote the textbook, “Cosmetic Dermatology: Principles and Practice” (New York: McGraw-Hill, 2002), and a book for consumers, “The Skin Type Solution” (New York: Bantam Dell, 2006). She has contributed to the Cosmeceutical Critique column in Dermatology News since January 2001. Her latest book, “Cosmeceuticals and Cosmetic Ingredients,” was published in November 2014. Dr. Baumann has received funding for clinical grants from Allergan, Aveeno, Avon Products, Evolus, Galderma, GlaxoSmithKline, Kythera Biopharmaceuticals, Mary Kay, Medicis Pharmaceuticals, Neutrogena, Philosophy, Topix Pharmaceuticals, and Unilever.

White tea, like green tea, is derived from the plant Camellia sinensis, a member of the Theaceae family and the source of all the globally popular “true tea” beverages.

Of the four main true teas, green and white are unfermented (white is the least processed), black tea is fermented, and oolong tea is semifermented.^1,2,3 White tea actually comes from the tips of the green tea leaves or leaves that have not yet fully opened, with buds covered by fine white hair. As a commodity, white tea is more expensive than green tea because it is more difficult to obtain. EGCG [(-)epigallocatechin-3-O-gallate], the most abundant and biologically active polyphenolic catechin found in green tea, is also the constituent in white tea that accounts for its antioxidant properties.^4,5 Indeed, white tea is included in topical products for its antioxidant as well as antiseptic activity, and is considered a more potent antioxidant additive medium than green tea.^6,1

As an ingredient in a combination formula

White tea is included in the dietary supplement Imedeen Prime Renewal, along with fish protein polysaccharides, vitamins C and E, zinc, and extracts from soy, grape seed, chamomile, and tomato.

In 2006, Skovgaard et al. conducted a 6-month, double-blind, placebo-controlled randomized study on 80 healthy postmenopausal women (38 in the treatment group, 42 in the placebo group completed the study) to determine antiaging effects on the skin. Subjects took 2 tablets of the supplement or placebo twice daily. Clinical, photo, and ultrasound evaluations showed significantly greater improvements in the treatment group, compared with the placebo group, in the face (forehead, periocular, and perioral wrinkles; mottled pigmentation, laxity, sagging, dark circles under the eyes; and overall appearance), hands, and décolletage.⁷

Antioxidant and antiaging activity

In 2009, Thring et al. studied the antiaging and antioxidant characteristics of 23 plant extracts (from 21 species) by considering antielastase and anticollagenase activities. White tea was found to exhibit the greatest inhibitory activity against both elastase and collagenase, greater than burdock root and angelica in terms of antielastase activity, and greater than green tea, rose tincture, and lavender in relation to anticollagenase activity. The Trolox equivalent antioxidant capacity assay also showed that white tea displayed the highest antioxidant activity. The investigators noted the very high phenolic content of white tea in characterizing its potent inhibitory activity against enzymes that accelerate cutaneous aging.⁶

Earlier in 2009, Camouse et al. examined skin samples from volunteers or skin explants treated with topical white or green tea after ultraviolet exposure to ascertain that the antioxidant could prevent simulated solar radiation–induced damage to DNA and Langerhans cells. They noted that each product displayed a sun protection factor of 1, suggesting that the photoprotection conferred was not due to direct UV absorption. Both forms of topically applied tea extracts were equally effective and judged by the researchers to be potential photoprotective agents when used along with other substantiated approaches to skin protection. These findings provided the first reported evidence of topically applied white tea preventing UV-induced immunosuppression. The researchers further suggested that the color of white tea might render it more cosmetically desirable than green tea.⁸

It should be noted that a systematic review performed by Hunt et al. in 2010 of MEDLINE, Embase, CINAHL (Cumulative Index to Nursing and Allied Health Literature), CENTRAL (Cochrane Central Register of Controlled Trials), and AMED (Allied and Complementary Medicine Database) databases up to 2009 identified 11 randomized clinical or controlled clinical trials evaluating the effectiveness of botanical extracts for diminishing wrinkling and other signs of cutaneous aging. No significant reductions in wrinkling were associated with the use of green tea or Vitaphenol (a combination of green and white teas, mangosteen, and pomegranate extract). The authors noted, however, that all of the trials that they identified were characterized by poor methodologic quality.⁹

Thring et al. conducted an in vitro study in 2011 to evaluate the antioxidant and anti-inflammatory activity of white tea, rose, and witch hazel extracts in primary human skin fibroblasts. The investigators measured significant anticollagenase, antielastase, and antioxidant activities for the white tea extracts, which also spurred a significant reduction in the interleukin-8 amount synthesized by fibroblasts, compared with controls. They concluded that white tea (as well as the other extracts) yielded a protective effect on fibroblasts against damage induced by hydrogen peroxide exposure.¹⁰

In 2014, Azman et al. used the spin trap method and electron paramagnetic resonance (EPR) spectroscopy to show that among white tea constituents, EGCG and epicatechin-3-gallate (ECG) exhibit the greatest antiradical activity against the methoxy radical.¹

Conclusion

Tea is one of the most popular beverages in the world and is touted for its antioxidant and anticancer properties. While the ingredients of green tea polyphenols have inspired a spate of recent research, much is yet to be learned about the potential health benefits of white tea, which is even less processed. Some evidence appears to suggest that white tea may be shown to be more effective overall, and in the dermatologic realm, than green tea. I look forward to seeing more research.

References

1. J Agric Food Chem. 2014;62(1):5743-8.

2. Dermatol Surg. 2005;31(7 Pt 2):873-80.

3. Oxid Med Cell Longev. 2012:2012:560682.

4. Mol Cell Biochem. 2000;206(1-2):125-32.

5. Free Radic Biol Med. 1999;26(11-12):1427-35.

6. BMC Complement Altern Med. 2009;9:27.

7. Eur J Clin Nutr. 2006;60(10):1201-6.

8. Exp Dermatol. 2009;18(6):522-6.

9. Drugs Aging. 2010;27(12):973-85.

10. J Inflamm (Lond). 2011;8(1):27).

Dr. Baumann is chief executive officer of the Baumann Cosmetic & Research Institute in the Design District in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann wrote the textbook, “Cosmetic Dermatology: Principles and Practice” (New York: McGraw-Hill, 2002), and a book for consumers, “The Skin Type Solution” (New York: Bantam Dell, 2006). She has contributed to the Cosmeceutical Critique column in Dermatology News since January 2001. Her latest book, “Cosmeceuticals and Cosmetic Ingredients,” was published in November 2014. Dr. Baumann has received funding for clinical grants from Allergan, Aveeno, Avon Products, Evolus, Galderma, GlaxoSmithKline, Kythera Biopharmaceuticals, Mary Kay, Medicis Pharmaceuticals, Neutrogena, Philosophy, Topix Pharmaceuticals, and Unilever.

White tea, like green tea, is derived from the plant Camellia sinensis, a member of the Theaceae family and the source of all the globally popular “true tea” beverages.

Of the four main true teas, green and white are unfermented (white is the least processed), black tea is fermented, and oolong tea is semifermented.^1,2,3 White tea actually comes from the tips of the green tea leaves or leaves that have not yet fully opened, with buds covered by fine white hair. As a commodity, white tea is more expensive than green tea because it is more difficult to obtain. EGCG [(-)epigallocatechin-3-O-gallate], the most abundant and biologically active polyphenolic catechin found in green tea, is also the constituent in white tea that accounts for its antioxidant properties.^4,5 Indeed, white tea is included in topical products for its antioxidant as well as antiseptic activity, and is considered a more potent antioxidant additive medium than green tea.^6,1

As an ingredient in a combination formula

White tea is included in the dietary supplement Imedeen Prime Renewal, along with fish protein polysaccharides, vitamins C and E, zinc, and extracts from soy, grape seed, chamomile, and tomato.

In 2006, Skovgaard et al. conducted a 6-month, double-blind, placebo-controlled randomized study on 80 healthy postmenopausal women (38 in the treatment group, 42 in the placebo group completed the study) to determine antiaging effects on the skin. Subjects took 2 tablets of the supplement or placebo twice daily. Clinical, photo, and ultrasound evaluations showed significantly greater improvements in the treatment group, compared with the placebo group, in the face (forehead, periocular, and perioral wrinkles; mottled pigmentation, laxity, sagging, dark circles under the eyes; and overall appearance), hands, and décolletage.⁷

Antioxidant and antiaging activity

In 2009, Thring et al. studied the antiaging and antioxidant characteristics of 23 plant extracts (from 21 species) by considering antielastase and anticollagenase activities. White tea was found to exhibit the greatest inhibitory activity against both elastase and collagenase, greater than burdock root and angelica in terms of antielastase activity, and greater than green tea, rose tincture, and lavender in relation to anticollagenase activity. The Trolox equivalent antioxidant capacity assay also showed that white tea displayed the highest antioxidant activity. The investigators noted the very high phenolic content of white tea in characterizing its potent inhibitory activity against enzymes that accelerate cutaneous aging.⁶

Earlier in 2009, Camouse et al. examined skin samples from volunteers or skin explants treated with topical white or green tea after ultraviolet exposure to ascertain that the antioxidant could prevent simulated solar radiation–induced damage to DNA and Langerhans cells. They noted that each product displayed a sun protection factor of 1, suggesting that the photoprotection conferred was not due to direct UV absorption. Both forms of topically applied tea extracts were equally effective and judged by the researchers to be potential photoprotective agents when used along with other substantiated approaches to skin protection. These findings provided the first reported evidence of topically applied white tea preventing UV-induced immunosuppression. The researchers further suggested that the color of white tea might render it more cosmetically desirable than green tea.⁸

It should be noted that a systematic review performed by Hunt et al. in 2010 of MEDLINE, Embase, CINAHL (Cumulative Index to Nursing and Allied Health Literature), CENTRAL (Cochrane Central Register of Controlled Trials), and AMED (Allied and Complementary Medicine Database) databases up to 2009 identified 11 randomized clinical or controlled clinical trials evaluating the effectiveness of botanical extracts for diminishing wrinkling and other signs of cutaneous aging. No significant reductions in wrinkling were associated with the use of green tea or Vitaphenol (a combination of green and white teas, mangosteen, and pomegranate extract). The authors noted, however, that all of the trials that they identified were characterized by poor methodologic quality.⁹

Thring et al. conducted an in vitro study in 2011 to evaluate the antioxidant and anti-inflammatory activity of white tea, rose, and witch hazel extracts in primary human skin fibroblasts. The investigators measured significant anticollagenase, antielastase, and antioxidant activities for the white tea extracts, which also spurred a significant reduction in the interleukin-8 amount synthesized by fibroblasts, compared with controls. They concluded that white tea (as well as the other extracts) yielded a protective effect on fibroblasts against damage induced by hydrogen peroxide exposure.¹⁰

In 2014, Azman et al. used the spin trap method and electron paramagnetic resonance (EPR) spectroscopy to show that among white tea constituents, EGCG and epicatechin-3-gallate (ECG) exhibit the greatest antiradical activity against the methoxy radical.¹

Conclusion

Tea is one of the most popular beverages in the world and is touted for its antioxidant and anticancer properties. While the ingredients of green tea polyphenols have inspired a spate of recent research, much is yet to be learned about the potential health benefits of white tea, which is even less processed. Some evidence appears to suggest that white tea may be shown to be more effective overall, and in the dermatologic realm, than green tea. I look forward to seeing more research.

References

1. J Agric Food Chem. 2014;62(1):5743-8.

2. Dermatol Surg. 2005;31(7 Pt 2):873-80.

3. Oxid Med Cell Longev. 2012:2012:560682.

4. Mol Cell Biochem. 2000;206(1-2):125-32.

5. Free Radic Biol Med. 1999;26(11-12):1427-35.

6. BMC Complement Altern Med. 2009;9:27.

7. Eur J Clin Nutr. 2006;60(10):1201-6.

8. Exp Dermatol. 2009;18(6):522-6.

9. Drugs Aging. 2010;27(12):973-85.

10. J Inflamm (Lond). 2011;8(1):27).

Dr. Baumann is chief executive officer of the Baumann Cosmetic & Research Institute in the Design District in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann wrote the textbook, “Cosmetic Dermatology: Principles and Practice” (New York: McGraw-Hill, 2002), and a book for consumers, “The Skin Type Solution” (New York: Bantam Dell, 2006). She has contributed to the Cosmeceutical Critique column in Dermatology News since January 2001. Her latest book, “Cosmeceuticals and Cosmetic Ingredients,” was published in November 2014. Dr. Baumann has received funding for clinical grants from Allergan, Aveeno, Avon Products, Evolus, Galderma, GlaxoSmithKline, Kythera Biopharmaceuticals, Mary Kay, Medicis Pharmaceuticals, Neutrogena, Philosophy, Topix Pharmaceuticals, and Unilever.

White tea, like green tea, is derived from the plant Camellia sinensis, a member of the Theaceae family and the source of all the globally popular “true tea” beverages.

Of the four main true teas, green and white are unfermented (white is the least processed), black tea is fermented, and oolong tea is semifermented.^1,2,3 White tea actually comes from the tips of the green tea leaves or leaves that have not yet fully opened, with buds covered by fine white hair. As a commodity, white tea is more expensive than green tea because it is more difficult to obtain. EGCG [(-)epigallocatechin-3-O-gallate], the most abundant and biologically active polyphenolic catechin found in green tea, is also the constituent in white tea that accounts for its antioxidant properties.^4,5 Indeed, white tea is included in topical products for its antioxidant as well as antiseptic activity, and is considered a more potent antioxidant additive medium than green tea.^6,1

As an ingredient in a combination formula

White tea is included in the dietary supplement Imedeen Prime Renewal, along with fish protein polysaccharides, vitamins C and E, zinc, and extracts from soy, grape seed, chamomile, and tomato.

In 2006, Skovgaard et al. conducted a 6-month, double-blind, placebo-controlled randomized study on 80 healthy postmenopausal women (38 in the treatment group, 42 in the placebo group completed the study) to determine antiaging effects on the skin. Subjects took 2 tablets of the supplement or placebo twice daily. Clinical, photo, and ultrasound evaluations showed significantly greater improvements in the treatment group, compared with the placebo group, in the face (forehead, periocular, and perioral wrinkles; mottled pigmentation, laxity, sagging, dark circles under the eyes; and overall appearance), hands, and décolletage.⁷

Antioxidant and antiaging activity

In 2009, Thring et al. studied the antiaging and antioxidant characteristics of 23 plant extracts (from 21 species) by considering antielastase and anticollagenase activities. White tea was found to exhibit the greatest inhibitory activity against both elastase and collagenase, greater than burdock root and angelica in terms of antielastase activity, and greater than green tea, rose tincture, and lavender in relation to anticollagenase activity. The Trolox equivalent antioxidant capacity assay also showed that white tea displayed the highest antioxidant activity. The investigators noted the very high phenolic content of white tea in characterizing its potent inhibitory activity against enzymes that accelerate cutaneous aging.⁶

Earlier in 2009, Camouse et al. examined skin samples from volunteers or skin explants treated with topical white or green tea after ultraviolet exposure to ascertain that the antioxidant could prevent simulated solar radiation–induced damage to DNA and Langerhans cells. They noted that each product displayed a sun protection factor of 1, suggesting that the photoprotection conferred was not due to direct UV absorption. Both forms of topically applied tea extracts were equally effective and judged by the researchers to be potential photoprotective agents when used along with other substantiated approaches to skin protection. These findings provided the first reported evidence of topically applied white tea preventing UV-induced immunosuppression. The researchers further suggested that the color of white tea might render it more cosmetically desirable than green tea.⁸

It should be noted that a systematic review performed by Hunt et al. in 2010 of MEDLINE, Embase, CINAHL (Cumulative Index to Nursing and Allied Health Literature), CENTRAL (Cochrane Central Register of Controlled Trials), and AMED (Allied and Complementary Medicine Database) databases up to 2009 identified 11 randomized clinical or controlled clinical trials evaluating the effectiveness of botanical extracts for diminishing wrinkling and other signs of cutaneous aging. No significant reductions in wrinkling were associated with the use of green tea or Vitaphenol (a combination of green and white teas, mangosteen, and pomegranate extract). The authors noted, however, that all of the trials that they identified were characterized by poor methodologic quality.⁹

Thring et al. conducted an in vitro study in 2011 to evaluate the antioxidant and anti-inflammatory activity of white tea, rose, and witch hazel extracts in primary human skin fibroblasts. The investigators measured significant anticollagenase, antielastase, and antioxidant activities for the white tea extracts, which also spurred a significant reduction in the interleukin-8 amount synthesized by fibroblasts, compared with controls. They concluded that white tea (as well as the other extracts) yielded a protective effect on fibroblasts against damage induced by hydrogen peroxide exposure.¹⁰

In 2014, Azman et al. used the spin trap method and electron paramagnetic resonance (EPR) spectroscopy to show that among white tea constituents, EGCG and epicatechin-3-gallate (ECG) exhibit the greatest antiradical activity against the methoxy radical.¹

Conclusion

Tea is one of the most popular beverages in the world and is touted for its antioxidant and anticancer properties. While the ingredients of green tea polyphenols have inspired a spate of recent research, much is yet to be learned about the potential health benefits of white tea, which is even less processed. Some evidence appears to suggest that white tea may be shown to be more effective overall, and in the dermatologic realm, than green tea. I look forward to seeing more research.

References

1. J Agric Food Chem. 2014;62(1):5743-8.

2. Dermatol Surg. 2005;31(7 Pt 2):873-80.

3. Oxid Med Cell Longev. 2012:2012:560682.

4. Mol Cell Biochem. 2000;206(1-2):125-32.

5. Free Radic Biol Med. 1999;26(11-12):1427-35.

6. BMC Complement Altern Med. 2009;9:27.

7. Eur J Clin Nutr. 2006;60(10):1201-6.

8. Exp Dermatol. 2009;18(6):522-6.

9. Drugs Aging. 2010;27(12):973-85.

10. J Inflamm (Lond). 2011;8(1):27).

Dr. Baumann is chief executive officer of the Baumann Cosmetic & Research Institute in the Design District in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann wrote the textbook, “Cosmetic Dermatology: Principles and Practice” (New York: McGraw-Hill, 2002), and a book for consumers, “The Skin Type Solution” (New York: Bantam Dell, 2006). She has contributed to the Cosmeceutical Critique column in Dermatology News since January 2001. Her latest book, “Cosmeceuticals and Cosmetic Ingredients,” was published in November 2014. Dr. Baumann has received funding for clinical grants from Allergan, Aveeno, Avon Products, Evolus, Galderma, GlaxoSmithKline, Kythera Biopharmaceuticals, Mary Kay, Medicis Pharmaceuticals, Neutrogena, Philosophy, Topix Pharmaceuticals, and Unilever.

A powerful endogenous antioxidant found most abundantly in mammalian tissues, especially brain and skeletal muscle tissue, carnosine is a dipeptide of alanine and histidine.^1,2,3,4,5.

Carnosine was first isolated in 1900 by the Russian scientist Gulewitsch as a substance extracted from muscle tissue.^6,4. L-carnosine (beta-alanyl-L-histidine) is the synthetic version identical to the natural form alpha-alanyl-L-histidine.⁷ Carnosine has long been reputed to confer immunomodulating, wound healing, antiglycating, and antineoplastic effects.² Several reports have shown that carnosine can accelerate the healing of surface skin wounds and burns.^4,8

Wound healing

An early study by Nagai et al. in 1986 on carnosine in wound healing showed that rats treated locally with carnosine exhibited greater tensile skin strength at an incision site after hydrocortisone had been administered to hinder healing. The investigators concluded that carnosine bolsters wound healing by stimulating early effusion by histamine and of collagen biosynthesis by beta-alanine. They also found that the compound significantly augmented granulation inhibited by cortisone, mitomycin C, 5-fluorouracil, and bleomycin.⁹

Studies by Fitzpatrick and Fisher in the early 1980s revealed that carnosine acts as a histidine reserve in relation to histamine production during trauma, suggesting a role for carnosine in wound healing.^10,11

In 2012, Ansurudeen et al. examined the effects of carnosine in wound healing in a diabetic mouse model. Carnosine was applied locally and injected daily, yielding significant amelioration in wound healing, with analysis revealing elevated expression of growth factors and cytokines implicated in wound healing. The investigators also observed that carnosine supported cell viability in the presence of high glucose in human dermal fibroblasts and microvascular endothelial cells in vitro.²

Other findings with implications for cutaneous therapy

In 2006, Babizhayev reported that the L-carnosine-related peptidomimetic N-acetylcarnosine (N-acetyl-beta-alanyl-L-histidine) can act as a timed-release (carrier) stable version of L-carnosine in cosmetic preparations, including lubricants.⁶ Babizhayev et al. have since claimed that they have developed a technology using imidazole-containing dipeptide-based compounds (including L-carnosine and derivatives) that enhances protein hydration in photoaged skin.^12,13,14

A double-blind comparative study conducted by Dieamant et al. in 2008 in 124 volunteers with sensitive skin aimed to evaluate the therapeutic potential of the combination of the antioxidant L-carnosine and neuromodulatory Rhodiola rosea. For 28 days, the groups of 62 received twice-daily applications of the 1% combination formulation or placebo. Skin barrier function (reduction of transepidermal water loss) improved in the treatment group, and favorable subjective responses regarding skin dryness were reported. Discomfort after the stinging test was also reduced. In vitro results showed that the release of proopiomelanocortin peptides was spurred by treatment, with the elevated levels of neuropeptides and cytokines produced by keratinocytes exposed to UV radiation returning to normal.¹⁵

Two years later, Renner et al. showed that carnosine hindered tumor growth in vivo in an NIH3T3-HER2/neu mouse model. They contended that this naturally occurring dipeptide warrants increased consideration and study for its potential as an anticancer agent.¹⁶

In 2012, Federici et al. conducted a randomized, evaluator-blinded, controlled comparative trial over 1month to assess the efficacy of twice-daily topical urea 5% with arginine and carnosine (Ureadin Rx) as compared with twice-daily application of a glycerol-based emollient topical product (Dexeryl) in treating xerosis in 40 type 2 diabetes patients (40-75 years of age). Use of the carnosine-containing formulation yielded significantly greater hydration and an 89% decline in Dryness Areas Severity Index (DASI) scores, compared with baseline. The DASI score after 4 weeks of treatment was much lower in the treatment group than the control group. The Visual Analog Scale (VAS) score was also significantly higher in the Ureadin group than the Dexeryl group. The investigators concluded that the topical application of a urea 5%, arginine, and carnosine cream enhances skin hydration and relieves dryness in type 2 diabetic patients in comparison with a control glycerol-based emollient formulation.¹⁷

Antiaging potential

In 1993, Reeve et al. showed that dietary or topically applied carnosine potentiated the contact hypersensitivity reaction in hairless mice and prevented the systemic inhibition of this reaction after dorsal skin exposure to UVB. Carnosine was found to also prevent the systemic suppression provoked by the topical application of a lotion containing cis-urocanic acid.³

Carnosine was a key active ingredient in antiaging products evaluated by Kaczvinsky et al. in 2009 in two double-blind, randomized, controlled, split-face studies. The researchers used the Fast Optical in vivo Topometry of Human Skin (FOITS) technique to measure changes in periorbital wrinkles in the two studies in women between the ages of 30 and 70 years old (study 1, n = 42; study 2, n = 35). They reported that 4 weeks of treatment with the test products, which contained niacinamide, the peptides Pal-KT and Pal-KTTKS, and carnosine, ameliorated periorbital skin, enhancing smoothness and diminishing larger wrinkle depth.¹⁸

In 2012, Babizhayev et al. conducted a 4-month randomized, double-blind, controlled study with 42 subjects to evaluate the effects on skin aging of oral nonhydrolyzed carnosine (Can-C Plus formulation). Skin parameters exhibited a consistent and significant improvement during 3 months of supplementation in the treatment group, compared with the placebo group, with overall skin appearance enhanced and fine lines diminished based on visual inspection. There were no reports of adverse effects. The investigators concluded that supplementation with nonhydrolyzed carnosine or carcinine in patented oral formulations has potential as an agent for antiaging purposes.¹⁹

Two years later, Emanuele et al. conducted an experimental double-blind irradiation study to compare a complex novel topical product (TPF50) consisting of three active ingredients (traditional physical sunscreens, SPF 50; a liposome-encapsulated DNA repair enzymes complex – photolyase, endonuclease, and 8-oxoguanine glycosylase [OGG1]; and a robust antioxidant complex containing carnosine, arazine, and ergothionine) to available DNA repair and antioxidant and growth factor topical products. They found that the new topical agent was the most effective product in reducing three molecular markers (cyclobutane pyrimidine dimers, protein carbonylation, and 8-oxo-7,8-dihydro-2’-deoxyguanosine) in human skin biopsies. The researchers concluded that the carnosine-containing formulation enhances the genomic and proteomic integrity of skin cells after continual UV exposure, suggesting its potential efficacy in lowering the risk of UV-induced cutaneous aging and nonmelanoma skin cancer.²⁰

Conclusion

Carnosine is an intriguing compound with well-documented antioxidant and wound healing activity. While more research is necessary to determine its wider applications in dermatology, recent work in formulating topical products to impart antiaging effects appears to show promise.

References

1. Nutr. Res. Pract. 2011;5:421-8.

2. Amino Acids 2012;43:127-34.

3. Immunology 1993;78:99-104.

4. Mol. Aspects Med. 1992;13:379-444.

5. Am. J. Ther. 2012;19:e69-89.

6. Life Sci. 2006;78:2343-57.

7. J. Cosmet. Dermatol. 2004;3:26-34.

8. Nihon Yakurigaku Zasshi. 1992;100:165-72.

9. Surgery 1986;100:815-21.

10. Surgery 1982;91:430-4.

11. Surgery 1982;91:56-60.

12. Int. J. Cosmet. Sci. 2011;33:1-16.

13. Crit. Rev. Ther. Drug Carrier Syst. 2011;28:203-53.

14. Crit. Rev. Ther. Drug Carrier Syst. 2010;27:85-154.

15. J. Cosmet. Dermatol. 2008;7:112-9.

16. Mol. Cancer 2010;9:2.

17. BMC Dermatol. 2012;12:16.

18. J. Cosmet. Dermatol. 2009;8:228-33.

19. J. Dermatolog. Treat. 2012;23:345-84.

20. J. Drugs Dermatol. 2014;13:309-14.

Dr. Baumann is chief executive officer of the Baumann Cosmetic & Research Institute in the Design District in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann wrote the textbook, “Cosmetic Dermatology: Principles and Practice” (New York: McGraw-Hill, 2002), and a book for consumers, “The Skin Type Solution” (New York: Bantam Dell, 2006). She has contributed to the Cosmeceutical Critique column in Dermatology News since January 2001. Her latest book, “Cosmeceuticals and Cosmetic Ingredients,” was published in November 2014. Dr. Baumann has received funding for clinical grants from Allergan, Aveeno, Avon Products, Evolus, Galderma, GlaxoSmithKline, Kythera Biopharmaceuticals, Mary Kay, Medicis Pharmaceuticals, Neutrogena, Philosophy, Topix Pharmaceuticals, and Unilever.

A powerful endogenous antioxidant found most abundantly in mammalian tissues, especially brain and skeletal muscle tissue, carnosine is a dipeptide of alanine and histidine.^1,2,3,4,5.

Carnosine was first isolated in 1900 by the Russian scientist Gulewitsch as a substance extracted from muscle tissue.^6,4. L-carnosine (beta-alanyl-L-histidine) is the synthetic version identical to the natural form alpha-alanyl-L-histidine.⁷ Carnosine has long been reputed to confer immunomodulating, wound healing, antiglycating, and antineoplastic effects.² Several reports have shown that carnosine can accelerate the healing of surface skin wounds and burns.^4,8

Wound healing

An early study by Nagai et al. in 1986 on carnosine in wound healing showed that rats treated locally with carnosine exhibited greater tensile skin strength at an incision site after hydrocortisone had been administered to hinder healing. The investigators concluded that carnosine bolsters wound healing by stimulating early effusion by histamine and of collagen biosynthesis by beta-alanine. They also found that the compound significantly augmented granulation inhibited by cortisone, mitomycin C, 5-fluorouracil, and bleomycin.⁹

Studies by Fitzpatrick and Fisher in the early 1980s revealed that carnosine acts as a histidine reserve in relation to histamine production during trauma, suggesting a role for carnosine in wound healing.^10,11

In 2012, Ansurudeen et al. examined the effects of carnosine in wound healing in a diabetic mouse model. Carnosine was applied locally and injected daily, yielding significant amelioration in wound healing, with analysis revealing elevated expression of growth factors and cytokines implicated in wound healing. The investigators also observed that carnosine supported cell viability in the presence of high glucose in human dermal fibroblasts and microvascular endothelial cells in vitro.²

Other findings with implications for cutaneous therapy

In 2006, Babizhayev reported that the L-carnosine-related peptidomimetic N-acetylcarnosine (N-acetyl-beta-alanyl-L-histidine) can act as a timed-release (carrier) stable version of L-carnosine in cosmetic preparations, including lubricants.⁶ Babizhayev et al. have since claimed that they have developed a technology using imidazole-containing dipeptide-based compounds (including L-carnosine and derivatives) that enhances protein hydration in photoaged skin.^12,13,14

A double-blind comparative study conducted by Dieamant et al. in 2008 in 124 volunteers with sensitive skin aimed to evaluate the therapeutic potential of the combination of the antioxidant L-carnosine and neuromodulatory Rhodiola rosea. For 28 days, the groups of 62 received twice-daily applications of the 1% combination formulation or placebo. Skin barrier function (reduction of transepidermal water loss) improved in the treatment group, and favorable subjective responses regarding skin dryness were reported. Discomfort after the stinging test was also reduced. In vitro results showed that the release of proopiomelanocortin peptides was spurred by treatment, with the elevated levels of neuropeptides and cytokines produced by keratinocytes exposed to UV radiation returning to normal.¹⁵

Two years later, Renner et al. showed that carnosine hindered tumor growth in vivo in an NIH3T3-HER2/neu mouse model. They contended that this naturally occurring dipeptide warrants increased consideration and study for its potential as an anticancer agent.¹⁶

In 2012, Federici et al. conducted a randomized, evaluator-blinded, controlled comparative trial over 1month to assess the efficacy of twice-daily topical urea 5% with arginine and carnosine (Ureadin Rx) as compared with twice-daily application of a glycerol-based emollient topical product (Dexeryl) in treating xerosis in 40 type 2 diabetes patients (40-75 years of age). Use of the carnosine-containing formulation yielded significantly greater hydration and an 89% decline in Dryness Areas Severity Index (DASI) scores, compared with baseline. The DASI score after 4 weeks of treatment was much lower in the treatment group than the control group. The Visual Analog Scale (VAS) score was also significantly higher in the Ureadin group than the Dexeryl group. The investigators concluded that the topical application of a urea 5%, arginine, and carnosine cream enhances skin hydration and relieves dryness in type 2 diabetic patients in comparison with a control glycerol-based emollient formulation.¹⁷

Antiaging potential

In 1993, Reeve et al. showed that dietary or topically applied carnosine potentiated the contact hypersensitivity reaction in hairless mice and prevented the systemic inhibition of this reaction after dorsal skin exposure to UVB. Carnosine was found to also prevent the systemic suppression provoked by the topical application of a lotion containing cis-urocanic acid.³

Carnosine was a key active ingredient in antiaging products evaluated by Kaczvinsky et al. in 2009 in two double-blind, randomized, controlled, split-face studies. The researchers used the Fast Optical in vivo Topometry of Human Skin (FOITS) technique to measure changes in periorbital wrinkles in the two studies in women between the ages of 30 and 70 years old (study 1, n = 42; study 2, n = 35). They reported that 4 weeks of treatment with the test products, which contained niacinamide, the peptides Pal-KT and Pal-KTTKS, and carnosine, ameliorated periorbital skin, enhancing smoothness and diminishing larger wrinkle depth.¹⁸

In 2012, Babizhayev et al. conducted a 4-month randomized, double-blind, controlled study with 42 subjects to evaluate the effects on skin aging of oral nonhydrolyzed carnosine (Can-C Plus formulation). Skin parameters exhibited a consistent and significant improvement during 3 months of supplementation in the treatment group, compared with the placebo group, with overall skin appearance enhanced and fine lines diminished based on visual inspection. There were no reports of adverse effects. The investigators concluded that supplementation with nonhydrolyzed carnosine or carcinine in patented oral formulations has potential as an agent for antiaging purposes.¹⁹

Two years later, Emanuele et al. conducted an experimental double-blind irradiation study to compare a complex novel topical product (TPF50) consisting of three active ingredients (traditional physical sunscreens, SPF 50; a liposome-encapsulated DNA repair enzymes complex – photolyase, endonuclease, and 8-oxoguanine glycosylase [OGG1]; and a robust antioxidant complex containing carnosine, arazine, and ergothionine) to available DNA repair and antioxidant and growth factor topical products. They found that the new topical agent was the most effective product in reducing three molecular markers (cyclobutane pyrimidine dimers, protein carbonylation, and 8-oxo-7,8-dihydro-2’-deoxyguanosine) in human skin biopsies. The researchers concluded that the carnosine-containing formulation enhances the genomic and proteomic integrity of skin cells after continual UV exposure, suggesting its potential efficacy in lowering the risk of UV-induced cutaneous aging and nonmelanoma skin cancer.²⁰

Conclusion

Carnosine is an intriguing compound with well-documented antioxidant and wound healing activity. While more research is necessary to determine its wider applications in dermatology, recent work in formulating topical products to impart antiaging effects appears to show promise.

References

1. Nutr. Res. Pract. 2011;5:421-8.

2. Amino Acids 2012;43:127-34.

3. Immunology 1993;78:99-104.

4. Mol. Aspects Med. 1992;13:379-444.

5. Am. J. Ther. 2012;19:e69-89.

6. Life Sci. 2006;78:2343-57.

7. J. Cosmet. Dermatol. 2004;3:26-34.

8. Nihon Yakurigaku Zasshi. 1992;100:165-72.

9. Surgery 1986;100:815-21.

10. Surgery 1982;91:430-4.

11. Surgery 1982;91:56-60.

12. Int. J. Cosmet. Sci. 2011;33:1-16.

13. Crit. Rev. Ther. Drug Carrier Syst. 2011;28:203-53.

14. Crit. Rev. Ther. Drug Carrier Syst. 2010;27:85-154.

15. J. Cosmet. Dermatol. 2008;7:112-9.

16. Mol. Cancer 2010;9:2.

17. BMC Dermatol. 2012;12:16.

18. J. Cosmet. Dermatol. 2009;8:228-33.

19. J. Dermatolog. Treat. 2012;23:345-84.

20. J. Drugs Dermatol. 2014;13:309-14.

Dr. Baumann is chief executive officer of the Baumann Cosmetic & Research Institute in the Design District in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann wrote the textbook, “Cosmetic Dermatology: Principles and Practice” (New York: McGraw-Hill, 2002), and a book for consumers, “The Skin Type Solution” (New York: Bantam Dell, 2006). She has contributed to the Cosmeceutical Critique column in Dermatology News since January 2001. Her latest book, “Cosmeceuticals and Cosmetic Ingredients,” was published in November 2014. Dr. Baumann has received funding for clinical grants from Allergan, Aveeno, Avon Products, Evolus, Galderma, GlaxoSmithKline, Kythera Biopharmaceuticals, Mary Kay, Medicis Pharmaceuticals, Neutrogena, Philosophy, Topix Pharmaceuticals, and Unilever.

A powerful endogenous antioxidant found most abundantly in mammalian tissues, especially brain and skeletal muscle tissue, carnosine is a dipeptide of alanine and histidine.^1,2,3,4,5.

Carnosine was first isolated in 1900 by the Russian scientist Gulewitsch as a substance extracted from muscle tissue.^6,4. L-carnosine (beta-alanyl-L-histidine) is the synthetic version identical to the natural form alpha-alanyl-L-histidine.⁷ Carnosine has long been reputed to confer immunomodulating, wound healing, antiglycating, and antineoplastic effects.² Several reports have shown that carnosine can accelerate the healing of surface skin wounds and burns.^4,8

Wound healing

An early study by Nagai et al. in 1986 on carnosine in wound healing showed that rats treated locally with carnosine exhibited greater tensile skin strength at an incision site after hydrocortisone had been administered to hinder healing. The investigators concluded that carnosine bolsters wound healing by stimulating early effusion by histamine and of collagen biosynthesis by beta-alanine. They also found that the compound significantly augmented granulation inhibited by cortisone, mitomycin C, 5-fluorouracil, and bleomycin.⁹

Studies by Fitzpatrick and Fisher in the early 1980s revealed that carnosine acts as a histidine reserve in relation to histamine production during trauma, suggesting a role for carnosine in wound healing.^10,11

In 2012, Ansurudeen et al. examined the effects of carnosine in wound healing in a diabetic mouse model. Carnosine was applied locally and injected daily, yielding significant amelioration in wound healing, with analysis revealing elevated expression of growth factors and cytokines implicated in wound healing. The investigators also observed that carnosine supported cell viability in the presence of high glucose in human dermal fibroblasts and microvascular endothelial cells in vitro.²

Other findings with implications for cutaneous therapy

In 2006, Babizhayev reported that the L-carnosine-related peptidomimetic N-acetylcarnosine (N-acetyl-beta-alanyl-L-histidine) can act as a timed-release (carrier) stable version of L-carnosine in cosmetic preparations, including lubricants.⁶ Babizhayev et al. have since claimed that they have developed a technology using imidazole-containing dipeptide-based compounds (including L-carnosine and derivatives) that enhances protein hydration in photoaged skin.^12,13,14

A double-blind comparative study conducted by Dieamant et al. in 2008 in 124 volunteers with sensitive skin aimed to evaluate the therapeutic potential of the combination of the antioxidant L-carnosine and neuromodulatory Rhodiola rosea. For 28 days, the groups of 62 received twice-daily applications of the 1% combination formulation or placebo. Skin barrier function (reduction of transepidermal water loss) improved in the treatment group, and favorable subjective responses regarding skin dryness were reported. Discomfort after the stinging test was also reduced. In vitro results showed that the release of proopiomelanocortin peptides was spurred by treatment, with the elevated levels of neuropeptides and cytokines produced by keratinocytes exposed to UV radiation returning to normal.¹⁵

Two years later, Renner et al. showed that carnosine hindered tumor growth in vivo in an NIH3T3-HER2/neu mouse model. They contended that this naturally occurring dipeptide warrants increased consideration and study for its potential as an anticancer agent.¹⁶

In 2012, Federici et al. conducted a randomized, evaluator-blinded, controlled comparative trial over 1month to assess the efficacy of twice-daily topical urea 5% with arginine and carnosine (Ureadin Rx) as compared with twice-daily application of a glycerol-based emollient topical product (Dexeryl) in treating xerosis in 40 type 2 diabetes patients (40-75 years of age). Use of the carnosine-containing formulation yielded significantly greater hydration and an 89% decline in Dryness Areas Severity Index (DASI) scores, compared with baseline. The DASI score after 4 weeks of treatment was much lower in the treatment group than the control group. The Visual Analog Scale (VAS) score was also significantly higher in the Ureadin group than the Dexeryl group. The investigators concluded that the topical application of a urea 5%, arginine, and carnosine cream enhances skin hydration and relieves dryness in type 2 diabetic patients in comparison with a control glycerol-based emollient formulation.¹⁷

Antiaging potential

In 1993, Reeve et al. showed that dietary or topically applied carnosine potentiated the contact hypersensitivity reaction in hairless mice and prevented the systemic inhibition of this reaction after dorsal skin exposure to UVB. Carnosine was found to also prevent the systemic suppression provoked by the topical application of a lotion containing cis-urocanic acid.³

Carnosine was a key active ingredient in antiaging products evaluated by Kaczvinsky et al. in 2009 in two double-blind, randomized, controlled, split-face studies. The researchers used the Fast Optical in vivo Topometry of Human Skin (FOITS) technique to measure changes in periorbital wrinkles in the two studies in women between the ages of 30 and 70 years old (study 1, n = 42; study 2, n = 35). They reported that 4 weeks of treatment with the test products, which contained niacinamide, the peptides Pal-KT and Pal-KTTKS, and carnosine, ameliorated periorbital skin, enhancing smoothness and diminishing larger wrinkle depth.¹⁸

In 2012, Babizhayev et al. conducted a 4-month randomized, double-blind, controlled study with 42 subjects to evaluate the effects on skin aging of oral nonhydrolyzed carnosine (Can-C Plus formulation). Skin parameters exhibited a consistent and significant improvement during 3 months of supplementation in the treatment group, compared with the placebo group, with overall skin appearance enhanced and fine lines diminished based on visual inspection. There were no reports of adverse effects. The investigators concluded that supplementation with nonhydrolyzed carnosine or carcinine in patented oral formulations has potential as an agent for antiaging purposes.¹⁹

Two years later, Emanuele et al. conducted an experimental double-blind irradiation study to compare a complex novel topical product (TPF50) consisting of three active ingredients (traditional physical sunscreens, SPF 50; a liposome-encapsulated DNA repair enzymes complex – photolyase, endonuclease, and 8-oxoguanine glycosylase [OGG1]; and a robust antioxidant complex containing carnosine, arazine, and ergothionine) to available DNA repair and antioxidant and growth factor topical products. They found that the new topical agent was the most effective product in reducing three molecular markers (cyclobutane pyrimidine dimers, protein carbonylation, and 8-oxo-7,8-dihydro-2’-deoxyguanosine) in human skin biopsies. The researchers concluded that the carnosine-containing formulation enhances the genomic and proteomic integrity of skin cells after continual UV exposure, suggesting its potential efficacy in lowering the risk of UV-induced cutaneous aging and nonmelanoma skin cancer.²⁰

Conclusion

Carnosine is an intriguing compound with well-documented antioxidant and wound healing activity. While more research is necessary to determine its wider applications in dermatology, recent work in formulating topical products to impart antiaging effects appears to show promise.

References

1. Nutr. Res. Pract. 2011;5:421-8.

2. Amino Acids 2012;43:127-34.

3. Immunology 1993;78:99-104.

4. Mol. Aspects Med. 1992;13:379-444.

5. Am. J. Ther. 2012;19:e69-89.

6. Life Sci. 2006;78:2343-57.

7. J. Cosmet. Dermatol. 2004;3:26-34.

8. Nihon Yakurigaku Zasshi. 1992;100:165-72.

9. Surgery 1986;100:815-21.

10. Surgery 1982;91:430-4.

11. Surgery 1982;91:56-60.

12. Int. J. Cosmet. Sci. 2011;33:1-16.

13. Crit. Rev. Ther. Drug Carrier Syst. 2011;28:203-53.

14. Crit. Rev. Ther. Drug Carrier Syst. 2010;27:85-154.

15. J. Cosmet. Dermatol. 2008;7:112-9.

16. Mol. Cancer 2010;9:2.

17. BMC Dermatol. 2012;12:16.

18. J. Cosmet. Dermatol. 2009;8:228-33.

19. J. Dermatolog. Treat. 2012;23:345-84.

20. J. Drugs Dermatol. 2014;13:309-14.

Dr. Baumann is chief executive officer of the Baumann Cosmetic & Research Institute in the Design District in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann wrote the textbook, “Cosmetic Dermatology: Principles and Practice” (New York: McGraw-Hill, 2002), and a book for consumers, “The Skin Type Solution” (New York: Bantam Dell, 2006). She has contributed to the Cosmeceutical Critique column in Dermatology News since January 2001. Her latest book, “Cosmeceuticals and Cosmetic Ingredients,” was published in November 2014. Dr. Baumann has received funding for clinical grants from Allergan, Aveeno, Avon Products, Evolus, Galderma, GlaxoSmithKline, Kythera Biopharmaceuticals, Mary Kay, Medicis Pharmaceuticals, Neutrogena, Philosophy, Topix Pharmaceuticals, and Unilever.