User login
Terminalia chebula
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
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
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
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
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
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
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
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.
Royal jelly
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
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.
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
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.
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
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.
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.
Melia azedarach
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.
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.
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.
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
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.
Carnosine
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.
4. Mol. Aspects Med. 1992;13:379-444.
5. Am. J. Ther. 2012;19:e69-89.
7. J. Cosmet. Dermatol. 2004;3:26-34.
8. Nihon Yakurigaku Zasshi. 1992;100:165-72.
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.
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.
4. Mol. Aspects Med. 1992;13:379-444.
5. Am. J. Ther. 2012;19:e69-89.
7. J. Cosmet. Dermatol. 2004;3:26-34.
8. Nihon Yakurigaku Zasshi. 1992;100:165-72.
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.
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.
4. Mol. Aspects Med. 1992;13:379-444.
5. Am. J. Ther. 2012;19:e69-89.
7. J. Cosmet. Dermatol. 2004;3:26-34.
8. Nihon Yakurigaku Zasshi. 1992;100:165-72.
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.
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.
Patchouli
Pogostemon cablin, known in the West as patchouli or guang huo-xiang in China, is a long-time staple in traditional Chinese medicine for various indications, particularly gastrointestinal and skin disorders1.
Patchouli oil, which contains several mono- and sesquiterpenoids, alkaloids, and flavonoids, is thought to possess significant anti-inflammatory and antioxidant qualities2.In fact, it is reputed to impart antiviral, antioxidant, anti-inflammatory, and analgesic effects, and is also known to protect intestinal barrier function3. Peng et al. have found that patchouli oil exerts significant antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA)4.
After a comprehensive 2013 review, Chen et al. deemed P. cablin to have potential clinical benefits as an effective adaptogenic herbal treatment3. It is thought to have some antiacne properties as well1. Further, P. cablin is among the Top 10 most-often-used traditional Chinese medicine prescriptions for skin care and appearance1.
In Brazil, China, Indonesia, and Malaysia, P. cablin is cultivated for its essential oil, which plays an important role in the perfume industry. Patchouli essential oil, featured in perfumes, soaps, cosmetics, and as incense, is used by aromatherapists for its calming and reviving effects. The essential oil has also been shown to impart antioxidant activity5.
In 2014, Lin et al. studied the protective effects of P. cablin essential oil against ultraviolet (UV)-induced skin photoaging in mice. The researchers applied patchouli oil for 2 hours before UV exposure to the dorsal depilated skin of mice. They found that patchouli oil doses of 6 mg/mouse and 9 mg/mouse significantly suppressed skin wrinkle formation, mitigated skin elasticity impairment, and augmented collagen content (21.9% and 26.3%, respectively). The same doses also yielded significant reductions in epidermal thickness and malondialdehyde content, and blocked the disruption of collagen and elastic fibers. Patchouli oil treatment also resulted in the up-regulation of the antioxidant enzymes superoxide dismutase, glutathione peroxidase, and catalase. The investigators concluded that patchouli oil, perhaps due to its antioxidant characteristics, and sesquiterpene constituents in particular, was effective in preventing photoaging in mice, and warrants attention as a potential agent to hinder photoaging in humans1.
Feng et al. also investigated the effects of topically applied patchouli alcohol on UV-induced photoaging in mice that year. For 9 weeks, investigators applied patchouli oil solution or a vehicle to the depilated dorsal skin of 6-week-old mice. They found that patchouli oil significantly hastened the recovery of UV-induced skin lesions, which they ascribed to the antioxidant and anti-inflammatory activity of the agent and its down-regulation of the expression of matrix metalloproteinase (MMP)-1 and MMP-32.
Antimicrobial and mosquito repellent activity
In a 2005 study by Trongtokit et al. of the mosquito-repellent activity of 38 essential oils at three concentrations (10%, 50%, or undiluted) against the mosquito Aedes aegypti under laboratory conditions using human volunteers, undiluted P. cablin oil was one of four [along with Cymbopogon nardus (citronella), Syzygium aromaticum (clove), and Zanthoxylum limonella (Thai name: makaen)] undiluted oils to yield an effect, 2 hours of full repellency. The investigators then tested the same concentrations of these oils for repellency against Culex quinquefasciatus (the Southern house mosquito) and Anopheles dirus (the mosquito considered to be a vector of malaria in Asian forested zones. The undiluted oils provided the greatest protection, with clove oil rendering the most durable repellency6.
Photoaging
Wu et al. determined the acaricidal activity of compounds extracted from patchouli oil against the house dust mite (Dermatophagoides farinae) in 2012. They isolated 2-(1,3-dihydroxy-but-2-enylidene)-6-methyl-3-oxo-heptanoic acid (DHEMH), the hydrolysate of pogostone, and 15 other constituents in patchouli oil, ultimately ascertaining that DHEMH and patchouli oil itself were the most toxic substances to D. farinae. The investigators concluded that patchouli oil and DHEMH warrant consideration and more study for their acaricidal potential as environmentally friendly, effective, and simple fumigant alternatives to chemical agents7.
In 2013, Yang et al. used molecular docking technology to evaluate the antibacterial activity of patchouli oil in vitro. They identified 26 compounds in patchouli oil displaying antibacterial activity, with pogostone and (-)-patchouli alcohol exhibiting the strongest activity8. Later that year, Yang et al. used the same technology to establish that Herba pogostemonis oil exhibited potent antibacterial effects, especially the constituents pogostone and (-)-Herba pogostemonis alcohol9. Raharjo and Fatchiyah also used molecular docking tools and Chimera 1.7s viewer software in a virtual screening of compounds from patchouli oil, concluding that alpha-patchouli alcohol is a potential inhibitor of the cyclo-oxygenase (COX)-1 enzyme. This is notable given the pivotal role of COX-1 in the inflammatory response10.
The next year, Peng et al. isolated one of the primary constituents of patchouli oil, pogostone, and assessed its antibacterial activity in vitro and in vivo. They found that pogostone suppressed both gram-negative and gram-positive bacteria in vitro. The researchers noted that pogostone was active against some drug-resistant bacteria (such as MRSA). Via intraperitoneal injection, pogostone displayed antibacterial activity in male and female Kunming mice against Escherichia coli and MRSA. At concentrations of 50 and 100 mg/kg, 90% of the mice infected with E. coli were protected; 60% of the mice at 25 mg/kg were protected. For mice with MRSA, 60% were protected at a dose of 100 mg/kg and 50% at a dose of 50 mg/kg. The investigators concluded that pogostone is a viable antibacterial agent for clinical use4.
Transdermal delivery
A 2008 study by Luo et al. showed that patchouli oil was among three volatile oils that improved the skin penetration of the flavonoids baicalin11. It was less effective than several compounds, including clove oil, camphor, menthol, and oleic acid, as a transdermal enhancer in a subsequent study by Zheng et al.12.
Conclusion
Patchouli oil continues to be used today in traditional Chinese medicine. In the West, the established literature on Pogostemon cablin is thin, but what has emerged recently, particularly studies on the protection against photoaging in mice, supports the continued investigation of this ancient herb to determine its potential role in dermatologic practice. As it is, much more research is necessary.
References
1. J Ethnopharmacol. 2014;154(2):408-18.
2. Eur J Pharm Sci. 2014;63:113-23.
3. Expert Opin Investig Drugs. 2013;22(2):245-57.
4. Chin Med J. (Engl) 2014;127(23):4001-5.
5. J Agric Food Chem. 2007;55(5):1737-42
6. Phytother Res. 2005;19(4):303-9.
7. Chem Pharm Bull (Tokyo). 2012;60(2):178-82.
8. Iran J Pharm Res. 2013 Summer;12(3):307-16.
9. Pak J Pharm Sci. 2013;26(6):1173-9.
10. Bioinformation 2013;9(6):321-4.
11. Zhong Yao Cai. 2008;31(11):1721-4
12. Zhongguo Zhong Yao Za Zhi. 2009;34(20):2599-603.
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.
Pogostemon cablin, known in the West as patchouli or guang huo-xiang in China, is a long-time staple in traditional Chinese medicine for various indications, particularly gastrointestinal and skin disorders1.
Patchouli oil, which contains several mono- and sesquiterpenoids, alkaloids, and flavonoids, is thought to possess significant anti-inflammatory and antioxidant qualities2.In fact, it is reputed to impart antiviral, antioxidant, anti-inflammatory, and analgesic effects, and is also known to protect intestinal barrier function3. Peng et al. have found that patchouli oil exerts significant antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA)4.
After a comprehensive 2013 review, Chen et al. deemed P. cablin to have potential clinical benefits as an effective adaptogenic herbal treatment3. It is thought to have some antiacne properties as well1. Further, P. cablin is among the Top 10 most-often-used traditional Chinese medicine prescriptions for skin care and appearance1.
In Brazil, China, Indonesia, and Malaysia, P. cablin is cultivated for its essential oil, which plays an important role in the perfume industry. Patchouli essential oil, featured in perfumes, soaps, cosmetics, and as incense, is used by aromatherapists for its calming and reviving effects. The essential oil has also been shown to impart antioxidant activity5.
In 2014, Lin et al. studied the protective effects of P. cablin essential oil against ultraviolet (UV)-induced skin photoaging in mice. The researchers applied patchouli oil for 2 hours before UV exposure to the dorsal depilated skin of mice. They found that patchouli oil doses of 6 mg/mouse and 9 mg/mouse significantly suppressed skin wrinkle formation, mitigated skin elasticity impairment, and augmented collagen content (21.9% and 26.3%, respectively). The same doses also yielded significant reductions in epidermal thickness and malondialdehyde content, and blocked the disruption of collagen and elastic fibers. Patchouli oil treatment also resulted in the up-regulation of the antioxidant enzymes superoxide dismutase, glutathione peroxidase, and catalase. The investigators concluded that patchouli oil, perhaps due to its antioxidant characteristics, and sesquiterpene constituents in particular, was effective in preventing photoaging in mice, and warrants attention as a potential agent to hinder photoaging in humans1.
Feng et al. also investigated the effects of topically applied patchouli alcohol on UV-induced photoaging in mice that year. For 9 weeks, investigators applied patchouli oil solution or a vehicle to the depilated dorsal skin of 6-week-old mice. They found that patchouli oil significantly hastened the recovery of UV-induced skin lesions, which they ascribed to the antioxidant and anti-inflammatory activity of the agent and its down-regulation of the expression of matrix metalloproteinase (MMP)-1 and MMP-32.
Antimicrobial and mosquito repellent activity
In a 2005 study by Trongtokit et al. of the mosquito-repellent activity of 38 essential oils at three concentrations (10%, 50%, or undiluted) against the mosquito Aedes aegypti under laboratory conditions using human volunteers, undiluted P. cablin oil was one of four [along with Cymbopogon nardus (citronella), Syzygium aromaticum (clove), and Zanthoxylum limonella (Thai name: makaen)] undiluted oils to yield an effect, 2 hours of full repellency. The investigators then tested the same concentrations of these oils for repellency against Culex quinquefasciatus (the Southern house mosquito) and Anopheles dirus (the mosquito considered to be a vector of malaria in Asian forested zones. The undiluted oils provided the greatest protection, with clove oil rendering the most durable repellency6.
Photoaging
Wu et al. determined the acaricidal activity of compounds extracted from patchouli oil against the house dust mite (Dermatophagoides farinae) in 2012. They isolated 2-(1,3-dihydroxy-but-2-enylidene)-6-methyl-3-oxo-heptanoic acid (DHEMH), the hydrolysate of pogostone, and 15 other constituents in patchouli oil, ultimately ascertaining that DHEMH and patchouli oil itself were the most toxic substances to D. farinae. The investigators concluded that patchouli oil and DHEMH warrant consideration and more study for their acaricidal potential as environmentally friendly, effective, and simple fumigant alternatives to chemical agents7.
In 2013, Yang et al. used molecular docking technology to evaluate the antibacterial activity of patchouli oil in vitro. They identified 26 compounds in patchouli oil displaying antibacterial activity, with pogostone and (-)-patchouli alcohol exhibiting the strongest activity8. Later that year, Yang et al. used the same technology to establish that Herba pogostemonis oil exhibited potent antibacterial effects, especially the constituents pogostone and (-)-Herba pogostemonis alcohol9. Raharjo and Fatchiyah also used molecular docking tools and Chimera 1.7s viewer software in a virtual screening of compounds from patchouli oil, concluding that alpha-patchouli alcohol is a potential inhibitor of the cyclo-oxygenase (COX)-1 enzyme. This is notable given the pivotal role of COX-1 in the inflammatory response10.
The next year, Peng et al. isolated one of the primary constituents of patchouli oil, pogostone, and assessed its antibacterial activity in vitro and in vivo. They found that pogostone suppressed both gram-negative and gram-positive bacteria in vitro. The researchers noted that pogostone was active against some drug-resistant bacteria (such as MRSA). Via intraperitoneal injection, pogostone displayed antibacterial activity in male and female Kunming mice against Escherichia coli and MRSA. At concentrations of 50 and 100 mg/kg, 90% of the mice infected with E. coli were protected; 60% of the mice at 25 mg/kg were protected. For mice with MRSA, 60% were protected at a dose of 100 mg/kg and 50% at a dose of 50 mg/kg. The investigators concluded that pogostone is a viable antibacterial agent for clinical use4.
Transdermal delivery
A 2008 study by Luo et al. showed that patchouli oil was among three volatile oils that improved the skin penetration of the flavonoids baicalin11. It was less effective than several compounds, including clove oil, camphor, menthol, and oleic acid, as a transdermal enhancer in a subsequent study by Zheng et al.12.
Conclusion
Patchouli oil continues to be used today in traditional Chinese medicine. In the West, the established literature on Pogostemon cablin is thin, but what has emerged recently, particularly studies on the protection against photoaging in mice, supports the continued investigation of this ancient herb to determine its potential role in dermatologic practice. As it is, much more research is necessary.
References
1. J Ethnopharmacol. 2014;154(2):408-18.
2. Eur J Pharm Sci. 2014;63:113-23.
3. Expert Opin Investig Drugs. 2013;22(2):245-57.
4. Chin Med J. (Engl) 2014;127(23):4001-5.
5. J Agric Food Chem. 2007;55(5):1737-42
6. Phytother Res. 2005;19(4):303-9.
7. Chem Pharm Bull (Tokyo). 2012;60(2):178-82.
8. Iran J Pharm Res. 2013 Summer;12(3):307-16.
9. Pak J Pharm Sci. 2013;26(6):1173-9.
10. Bioinformation 2013;9(6):321-4.
11. Zhong Yao Cai. 2008;31(11):1721-4
12. Zhongguo Zhong Yao Za Zhi. 2009;34(20):2599-603.
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.
Pogostemon cablin, known in the West as patchouli or guang huo-xiang in China, is a long-time staple in traditional Chinese medicine for various indications, particularly gastrointestinal and skin disorders1.
Patchouli oil, which contains several mono- and sesquiterpenoids, alkaloids, and flavonoids, is thought to possess significant anti-inflammatory and antioxidant qualities2.In fact, it is reputed to impart antiviral, antioxidant, anti-inflammatory, and analgesic effects, and is also known to protect intestinal barrier function3. Peng et al. have found that patchouli oil exerts significant antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA)4.
After a comprehensive 2013 review, Chen et al. deemed P. cablin to have potential clinical benefits as an effective adaptogenic herbal treatment3. It is thought to have some antiacne properties as well1. Further, P. cablin is among the Top 10 most-often-used traditional Chinese medicine prescriptions for skin care and appearance1.
In Brazil, China, Indonesia, and Malaysia, P. cablin is cultivated for its essential oil, which plays an important role in the perfume industry. Patchouli essential oil, featured in perfumes, soaps, cosmetics, and as incense, is used by aromatherapists for its calming and reviving effects. The essential oil has also been shown to impart antioxidant activity5.
In 2014, Lin et al. studied the protective effects of P. cablin essential oil against ultraviolet (UV)-induced skin photoaging in mice. The researchers applied patchouli oil for 2 hours before UV exposure to the dorsal depilated skin of mice. They found that patchouli oil doses of 6 mg/mouse and 9 mg/mouse significantly suppressed skin wrinkle formation, mitigated skin elasticity impairment, and augmented collagen content (21.9% and 26.3%, respectively). The same doses also yielded significant reductions in epidermal thickness and malondialdehyde content, and blocked the disruption of collagen and elastic fibers. Patchouli oil treatment also resulted in the up-regulation of the antioxidant enzymes superoxide dismutase, glutathione peroxidase, and catalase. The investigators concluded that patchouli oil, perhaps due to its antioxidant characteristics, and sesquiterpene constituents in particular, was effective in preventing photoaging in mice, and warrants attention as a potential agent to hinder photoaging in humans1.
Feng et al. also investigated the effects of topically applied patchouli alcohol on UV-induced photoaging in mice that year. For 9 weeks, investigators applied patchouli oil solution or a vehicle to the depilated dorsal skin of 6-week-old mice. They found that patchouli oil significantly hastened the recovery of UV-induced skin lesions, which they ascribed to the antioxidant and anti-inflammatory activity of the agent and its down-regulation of the expression of matrix metalloproteinase (MMP)-1 and MMP-32.
Antimicrobial and mosquito repellent activity
In a 2005 study by Trongtokit et al. of the mosquito-repellent activity of 38 essential oils at three concentrations (10%, 50%, or undiluted) against the mosquito Aedes aegypti under laboratory conditions using human volunteers, undiluted P. cablin oil was one of four [along with Cymbopogon nardus (citronella), Syzygium aromaticum (clove), and Zanthoxylum limonella (Thai name: makaen)] undiluted oils to yield an effect, 2 hours of full repellency. The investigators then tested the same concentrations of these oils for repellency against Culex quinquefasciatus (the Southern house mosquito) and Anopheles dirus (the mosquito considered to be a vector of malaria in Asian forested zones. The undiluted oils provided the greatest protection, with clove oil rendering the most durable repellency6.
Photoaging
Wu et al. determined the acaricidal activity of compounds extracted from patchouli oil against the house dust mite (Dermatophagoides farinae) in 2012. They isolated 2-(1,3-dihydroxy-but-2-enylidene)-6-methyl-3-oxo-heptanoic acid (DHEMH), the hydrolysate of pogostone, and 15 other constituents in patchouli oil, ultimately ascertaining that DHEMH and patchouli oil itself were the most toxic substances to D. farinae. The investigators concluded that patchouli oil and DHEMH warrant consideration and more study for their acaricidal potential as environmentally friendly, effective, and simple fumigant alternatives to chemical agents7.
In 2013, Yang et al. used molecular docking technology to evaluate the antibacterial activity of patchouli oil in vitro. They identified 26 compounds in patchouli oil displaying antibacterial activity, with pogostone and (-)-patchouli alcohol exhibiting the strongest activity8. Later that year, Yang et al. used the same technology to establish that Herba pogostemonis oil exhibited potent antibacterial effects, especially the constituents pogostone and (-)-Herba pogostemonis alcohol9. Raharjo and Fatchiyah also used molecular docking tools and Chimera 1.7s viewer software in a virtual screening of compounds from patchouli oil, concluding that alpha-patchouli alcohol is a potential inhibitor of the cyclo-oxygenase (COX)-1 enzyme. This is notable given the pivotal role of COX-1 in the inflammatory response10.
The next year, Peng et al. isolated one of the primary constituents of patchouli oil, pogostone, and assessed its antibacterial activity in vitro and in vivo. They found that pogostone suppressed both gram-negative and gram-positive bacteria in vitro. The researchers noted that pogostone was active against some drug-resistant bacteria (such as MRSA). Via intraperitoneal injection, pogostone displayed antibacterial activity in male and female Kunming mice against Escherichia coli and MRSA. At concentrations of 50 and 100 mg/kg, 90% of the mice infected with E. coli were protected; 60% of the mice at 25 mg/kg were protected. For mice with MRSA, 60% were protected at a dose of 100 mg/kg and 50% at a dose of 50 mg/kg. The investigators concluded that pogostone is a viable antibacterial agent for clinical use4.
Transdermal delivery
A 2008 study by Luo et al. showed that patchouli oil was among three volatile oils that improved the skin penetration of the flavonoids baicalin11. It was less effective than several compounds, including clove oil, camphor, menthol, and oleic acid, as a transdermal enhancer in a subsequent study by Zheng et al.12.
Conclusion
Patchouli oil continues to be used today in traditional Chinese medicine. In the West, the established literature on Pogostemon cablin is thin, but what has emerged recently, particularly studies on the protection against photoaging in mice, supports the continued investigation of this ancient herb to determine its potential role in dermatologic practice. As it is, much more research is necessary.
References
1. J Ethnopharmacol. 2014;154(2):408-18.
2. Eur J Pharm Sci. 2014;63:113-23.
3. Expert Opin Investig Drugs. 2013;22(2):245-57.
4. Chin Med J. (Engl) 2014;127(23):4001-5.
5. J Agric Food Chem. 2007;55(5):1737-42
6. Phytother Res. 2005;19(4):303-9.
7. Chem Pharm Bull (Tokyo). 2012;60(2):178-82.
8. Iran J Pharm Res. 2013 Summer;12(3):307-16.
9. Pak J Pharm Sci. 2013;26(6):1173-9.
10. Bioinformation 2013;9(6):321-4.
11. Zhong Yao Cai. 2008;31(11):1721-4
12. Zhongguo Zhong Yao Za Zhi. 2009;34(20):2599-603.
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.
Black tea
Camellia sinensis, an evergreen tree belonging to the Theaceae family and used by human beings for approximately 4,000 years, is the source of the beverage tea, which is popular throughout the world, especially in Asia.1 Of the four main true teas (that is, derived from the tea plant C. sinensis), green and white are unfermented, black tea is fermented, and oolong tea is semifermented.2,3
Polyphenols, many of which act as strong antioxidants, are a diverse family of thousands of chemical substances found in plants. Theaflavins are black tea polyphenols with well-documented tumor-suppressing activity.4 In fact, they are thought to be the primary constituents of black tea responsible for conferring chemoprotection against cancer.5 Black tea, through oral administration and topical application, has been shown in the laboratory setting to protect skin from UV-induced erythema, premature aging, and cancer.6
Halder et al. have found that theaflavins and thearubigins, another key class of black tea polyphenols, can suppress A431 (human epidermoid carcinoma) and A375 (human malignant melanoma) cell proliferation without adversely impacting normal human epidermal keratinocytes. The researchers concluded that theaflavins and thearubigins appear to impart chemopreventive activity via cell cycle arrest and promotion of apoptosis in human skin cancer cells through a mitochondrial death cascade.7
In a 2005 English-language literature review, Thornfeldt cited green and black tea, as well as pomegranate, as the only ingredients supported by clinical trial evidence for effectiveness in treating extrinsic aging.2
Oral administration findings in animals and humans
More than 2 decades ago, Wang et al. found that the effects of orally administered black tea were comparable to those of green tea in suppressing UVB-induced skin carcinogenesis in 7,12-dimethylbenz[a]anthracene (DMBA)-initiated SKH-1 mice.8
In 1997, Lu et al. found that orally administered black tea inhibited the proliferation of skin tumors and enhanced apoptosis in nonmalignant and malignant skin tumors in female CD-1 mice with tumors initiated by the application of DMBA and promoted with 12-O-tetradecanoylphorbol-13-acetate (TPA).9 Record et al. reported in 1998 that black tea may confer greater protection than green tea against simulated solar irradiation.10
Hakim and Harris conducted a population-based case-control study in 2001 to assess the effects of the consumption of citrus peel and black tea on squamous cell skin cancer. They found that participants who reported intake of hot black tea and citrus peel had a significant reduction in the risk of squamous cell carcinoma. Further, they concluded that hot black tea and citrus peel displayed independent potential protection against SCC.11
Two years earlier, Zhao et al. used cultured keratinocytes and mouse and human skin to evaluate the effect of both orally and topically administered standardized black tea extract and its two major polyphenolic subfractions against UVB-induced photodamage. Topical pretreatment with the extract on SKH-1 hairless mice significantly lowered the incidence and severity of erythema and diminished skinfold thickness, compared with UVB-exposed nontreated mice. The black tea extract was similarly effective in human subjects. UVB-induced inflammation in murine as well as human skin also was reduced when the standardized extract was administered 5 minutes after UVB exposure. The investigators suggested that their findings indicated that black tea extracts have the capacity to mitigate UVB-generated erythema in human and murine skin.12
In 2011, George et al. assessed the chemopreventive effects of topical resveratrol and oral black tea polyphenols in blocking skin carcinogenesis in a two-stage mouse model initiated and promoted by DMBA and TPA, respectively. The combined treatment was found to reduce tumor incidence by approximately 89% (resveratrol alone, approximately 67%; black tea polyphenols alone, approximately 75%). Tumor volume and number also were significantly diminished by the synergistic combination, which, histologically, was noted for suppressing cellular proliferation and inducing apoptosis. The investigators concluded that oral black tea polyphenols combined with topical resveratrol exert greater chemopreventive activity than either compound alone and warrant study in trials for treating skin and other cancers.13
Animal studies on topical application
In 1997, Katiyar et al. investigated the anti-inflammatory effects of topically applied black tea polyphenols, primarily theaflavin gallates and (-)-epigallocatechin-3-gallate (EGCG), against TPA-induced inflammatory responses in murine skin. Significant inhibition against TPA-promoted induction of epidermal edema, hyperplasia, leukocyte infiltration, and proinflammatory cytokine expression was rendered by the preapplication of black tea polyphenols prior to TPA exposure. The investigators concluded that black tea polyphenols may be effective against human cutaneous inflammatory responses.14
Just over a decade later, Patel et al. investigated the in vivo antitumor-promoting effects of the most plentiful polymeric black tea polyphenols (thearubigins) in mice exposed to tumor-initiating DMBA and tumor-promoting TPA over a 40-week period. Pretreatment with topical thearubigins resulted in antipromoting effects in terms of latency, multiplicity, and incidence of skin papillomas. The black tea polyphenols also were found to reduce TPA-induced cell proliferation and epidermal cell apoptosis. The researchers attributed the protective effects of these compounds to their inhibitory impact on TPA-induced cellular proliferation.15
In 2011, Choi and Kim assessed the whitening effect of black tea water extract topically applied twice daily (6 days a week for 4 weeks) to UVB-induced hyperpigmented spots on the backs of brown guinea pigs. Treatment was divided into control (UVB and saline), vehicle control (UVB, propylene glycol, ethanol, and water), positive control (UVB and 2% hydroquinone), and two experimental groups (UVB and 1% black tea; UVB and 2% black tea). The investigators observed that the hyperpigmented spots treated with hydroquinone and black tea were clearly lighter than those treated by the control or vehicle-control groups. Histologic examination revealed that melanin pigmentation, melanocyte proliferation, and melanin production were significantly diminished in the groups treated with hydroquinone and both concentrations of black tea. The authors concluded that black tea suppresses melanocyte proliferation and melanosome synthesis in vivo, thus displaying the capacity to whiten skin in brown guinea pigs.16
In 2013, Yeh et al. found in nude mouse skin in vitro that niosomes appear to be feasible as a delivery vehicle for the dermal administration of black tea extracts as a sunscreen agent.1
Topical studies in humans
Building on findings 3 years earlier18, Türkoglu et al., in 2010, assessed the photoprotective effects of dermal gels produced from green and black tea aqueous extracts tested in vivo in the forearms of six volunteers exposed to artificial UV light (200-400 nm). In addition to the green tea and black tea gels, a 0.3% caffeine gel, a carbomer gel base, and a control were tested. The investigators reported no eruptions of UV-induced erythema in any of the black and green tea gel sites, but erythema was present to varying degrees at the areas treated with caffeine gel, carbomer gel, and control. The investigators concluded that the black and green tea extracts exhibited potent UV absorbance and that the formulated gels were effective in protecting the skin against UV-induced erythema. Further, the investigators suggested that these agents have the potential to protect against other harm caused by UV radiation, including photoaging.19
Conclusion
Though not as widely investigated as green tea, the therapeutic potential of black tea is of great interest. Although an abundance of laboratory evidence has emerged, clinical evidence is sparse. Nevertheless, laboratory data suggest the potential uses of black tea in the dermatologic realm and justify more human trials.
References
1. Cancer Lett. 1997 Mar 19;114(1-2):315-7.
2. Dermatol. Surg. 2005;31(7 Pt 2):873-80.
3. Oxid Med Cell Longev. 2012:2012:560682.
4. J Environ Pathol Toxicol Oncol. 2010;29(1):55-68.
5. Mol Carcinog. 2000 Jul;28(3):148-55.
6. Am J Clin Dermatol. 2010;11(4):247-67.
7. Carcinogenesis. 2008 Jan;29(1):129-38.
8. Cancer Res. 1994 Jul 1;54(13):3428-35.
9. Carcinogenesis. 1997 Nov;18(11):2163-9.
10. Mutat Res. 1998 Nov 9;422(1):191-9.
12. Photochem Photobiol. 1999 Oct;70(4):637-44.
13. PLoS One. 2011;6(8):e23395.
14. Carcinogenesis. 1997 Oct;18(10):1911-6.
15. Cell Prolif. 2008 Jun;41(3):532-53.
16. Toxicol Res. 2011 Sep;27(3):153-60.
17. Int J Dermatol. 2013 Feb;52(2):239-45.
18. Int J Cosmet Sci. 2007 Dec;29(6):437-42.
19. Drug Discov Ther. 2010 Oct;4(5):362-7.
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.
Camellia sinensis, an evergreen tree belonging to the Theaceae family and used by human beings for approximately 4,000 years, is the source of the beverage tea, which is popular throughout the world, especially in Asia.1 Of the four main true teas (that is, derived from the tea plant C. sinensis), green and white are unfermented, black tea is fermented, and oolong tea is semifermented.2,3
Polyphenols, many of which act as strong antioxidants, are a diverse family of thousands of chemical substances found in plants. Theaflavins are black tea polyphenols with well-documented tumor-suppressing activity.4 In fact, they are thought to be the primary constituents of black tea responsible for conferring chemoprotection against cancer.5 Black tea, through oral administration and topical application, has been shown in the laboratory setting to protect skin from UV-induced erythema, premature aging, and cancer.6
Halder et al. have found that theaflavins and thearubigins, another key class of black tea polyphenols, can suppress A431 (human epidermoid carcinoma) and A375 (human malignant melanoma) cell proliferation without adversely impacting normal human epidermal keratinocytes. The researchers concluded that theaflavins and thearubigins appear to impart chemopreventive activity via cell cycle arrest and promotion of apoptosis in human skin cancer cells through a mitochondrial death cascade.7
In a 2005 English-language literature review, Thornfeldt cited green and black tea, as well as pomegranate, as the only ingredients supported by clinical trial evidence for effectiveness in treating extrinsic aging.2
Oral administration findings in animals and humans
More than 2 decades ago, Wang et al. found that the effects of orally administered black tea were comparable to those of green tea in suppressing UVB-induced skin carcinogenesis in 7,12-dimethylbenz[a]anthracene (DMBA)-initiated SKH-1 mice.8
In 1997, Lu et al. found that orally administered black tea inhibited the proliferation of skin tumors and enhanced apoptosis in nonmalignant and malignant skin tumors in female CD-1 mice with tumors initiated by the application of DMBA and promoted with 12-O-tetradecanoylphorbol-13-acetate (TPA).9 Record et al. reported in 1998 that black tea may confer greater protection than green tea against simulated solar irradiation.10
Hakim and Harris conducted a population-based case-control study in 2001 to assess the effects of the consumption of citrus peel and black tea on squamous cell skin cancer. They found that participants who reported intake of hot black tea and citrus peel had a significant reduction in the risk of squamous cell carcinoma. Further, they concluded that hot black tea and citrus peel displayed independent potential protection against SCC.11
Two years earlier, Zhao et al. used cultured keratinocytes and mouse and human skin to evaluate the effect of both orally and topically administered standardized black tea extract and its two major polyphenolic subfractions against UVB-induced photodamage. Topical pretreatment with the extract on SKH-1 hairless mice significantly lowered the incidence and severity of erythema and diminished skinfold thickness, compared with UVB-exposed nontreated mice. The black tea extract was similarly effective in human subjects. UVB-induced inflammation in murine as well as human skin also was reduced when the standardized extract was administered 5 minutes after UVB exposure. The investigators suggested that their findings indicated that black tea extracts have the capacity to mitigate UVB-generated erythema in human and murine skin.12
In 2011, George et al. assessed the chemopreventive effects of topical resveratrol and oral black tea polyphenols in blocking skin carcinogenesis in a two-stage mouse model initiated and promoted by DMBA and TPA, respectively. The combined treatment was found to reduce tumor incidence by approximately 89% (resveratrol alone, approximately 67%; black tea polyphenols alone, approximately 75%). Tumor volume and number also were significantly diminished by the synergistic combination, which, histologically, was noted for suppressing cellular proliferation and inducing apoptosis. The investigators concluded that oral black tea polyphenols combined with topical resveratrol exert greater chemopreventive activity than either compound alone and warrant study in trials for treating skin and other cancers.13
Animal studies on topical application
In 1997, Katiyar et al. investigated the anti-inflammatory effects of topically applied black tea polyphenols, primarily theaflavin gallates and (-)-epigallocatechin-3-gallate (EGCG), against TPA-induced inflammatory responses in murine skin. Significant inhibition against TPA-promoted induction of epidermal edema, hyperplasia, leukocyte infiltration, and proinflammatory cytokine expression was rendered by the preapplication of black tea polyphenols prior to TPA exposure. The investigators concluded that black tea polyphenols may be effective against human cutaneous inflammatory responses.14
Just over a decade later, Patel et al. investigated the in vivo antitumor-promoting effects of the most plentiful polymeric black tea polyphenols (thearubigins) in mice exposed to tumor-initiating DMBA and tumor-promoting TPA over a 40-week period. Pretreatment with topical thearubigins resulted in antipromoting effects in terms of latency, multiplicity, and incidence of skin papillomas. The black tea polyphenols also were found to reduce TPA-induced cell proliferation and epidermal cell apoptosis. The researchers attributed the protective effects of these compounds to their inhibitory impact on TPA-induced cellular proliferation.15
In 2011, Choi and Kim assessed the whitening effect of black tea water extract topically applied twice daily (6 days a week for 4 weeks) to UVB-induced hyperpigmented spots on the backs of brown guinea pigs. Treatment was divided into control (UVB and saline), vehicle control (UVB, propylene glycol, ethanol, and water), positive control (UVB and 2% hydroquinone), and two experimental groups (UVB and 1% black tea; UVB and 2% black tea). The investigators observed that the hyperpigmented spots treated with hydroquinone and black tea were clearly lighter than those treated by the control or vehicle-control groups. Histologic examination revealed that melanin pigmentation, melanocyte proliferation, and melanin production were significantly diminished in the groups treated with hydroquinone and both concentrations of black tea. The authors concluded that black tea suppresses melanocyte proliferation and melanosome synthesis in vivo, thus displaying the capacity to whiten skin in brown guinea pigs.16
In 2013, Yeh et al. found in nude mouse skin in vitro that niosomes appear to be feasible as a delivery vehicle for the dermal administration of black tea extracts as a sunscreen agent.1
Topical studies in humans
Building on findings 3 years earlier18, Türkoglu et al., in 2010, assessed the photoprotective effects of dermal gels produced from green and black tea aqueous extracts tested in vivo in the forearms of six volunteers exposed to artificial UV light (200-400 nm). In addition to the green tea and black tea gels, a 0.3% caffeine gel, a carbomer gel base, and a control were tested. The investigators reported no eruptions of UV-induced erythema in any of the black and green tea gel sites, but erythema was present to varying degrees at the areas treated with caffeine gel, carbomer gel, and control. The investigators concluded that the black and green tea extracts exhibited potent UV absorbance and that the formulated gels were effective in protecting the skin against UV-induced erythema. Further, the investigators suggested that these agents have the potential to protect against other harm caused by UV radiation, including photoaging.19
Conclusion
Though not as widely investigated as green tea, the therapeutic potential of black tea is of great interest. Although an abundance of laboratory evidence has emerged, clinical evidence is sparse. Nevertheless, laboratory data suggest the potential uses of black tea in the dermatologic realm and justify more human trials.
References
1. Cancer Lett. 1997 Mar 19;114(1-2):315-7.
2. Dermatol. Surg. 2005;31(7 Pt 2):873-80.
3. Oxid Med Cell Longev. 2012:2012:560682.
4. J Environ Pathol Toxicol Oncol. 2010;29(1):55-68.
5. Mol Carcinog. 2000 Jul;28(3):148-55.
6. Am J Clin Dermatol. 2010;11(4):247-67.
7. Carcinogenesis. 2008 Jan;29(1):129-38.
8. Cancer Res. 1994 Jul 1;54(13):3428-35.
9. Carcinogenesis. 1997 Nov;18(11):2163-9.
10. Mutat Res. 1998 Nov 9;422(1):191-9.
12. Photochem Photobiol. 1999 Oct;70(4):637-44.
13. PLoS One. 2011;6(8):e23395.
14. Carcinogenesis. 1997 Oct;18(10):1911-6.
15. Cell Prolif. 2008 Jun;41(3):532-53.
16. Toxicol Res. 2011 Sep;27(3):153-60.
17. Int J Dermatol. 2013 Feb;52(2):239-45.
18. Int J Cosmet Sci. 2007 Dec;29(6):437-42.
19. Drug Discov Ther. 2010 Oct;4(5):362-7.
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.
Camellia sinensis, an evergreen tree belonging to the Theaceae family and used by human beings for approximately 4,000 years, is the source of the beverage tea, which is popular throughout the world, especially in Asia.1 Of the four main true teas (that is, derived from the tea plant C. sinensis), green and white are unfermented, black tea is fermented, and oolong tea is semifermented.2,3
Polyphenols, many of which act as strong antioxidants, are a diverse family of thousands of chemical substances found in plants. Theaflavins are black tea polyphenols with well-documented tumor-suppressing activity.4 In fact, they are thought to be the primary constituents of black tea responsible for conferring chemoprotection against cancer.5 Black tea, through oral administration and topical application, has been shown in the laboratory setting to protect skin from UV-induced erythema, premature aging, and cancer.6
Halder et al. have found that theaflavins and thearubigins, another key class of black tea polyphenols, can suppress A431 (human epidermoid carcinoma) and A375 (human malignant melanoma) cell proliferation without adversely impacting normal human epidermal keratinocytes. The researchers concluded that theaflavins and thearubigins appear to impart chemopreventive activity via cell cycle arrest and promotion of apoptosis in human skin cancer cells through a mitochondrial death cascade.7
In a 2005 English-language literature review, Thornfeldt cited green and black tea, as well as pomegranate, as the only ingredients supported by clinical trial evidence for effectiveness in treating extrinsic aging.2
Oral administration findings in animals and humans
More than 2 decades ago, Wang et al. found that the effects of orally administered black tea were comparable to those of green tea in suppressing UVB-induced skin carcinogenesis in 7,12-dimethylbenz[a]anthracene (DMBA)-initiated SKH-1 mice.8
In 1997, Lu et al. found that orally administered black tea inhibited the proliferation of skin tumors and enhanced apoptosis in nonmalignant and malignant skin tumors in female CD-1 mice with tumors initiated by the application of DMBA and promoted with 12-O-tetradecanoylphorbol-13-acetate (TPA).9 Record et al. reported in 1998 that black tea may confer greater protection than green tea against simulated solar irradiation.10
Hakim and Harris conducted a population-based case-control study in 2001 to assess the effects of the consumption of citrus peel and black tea on squamous cell skin cancer. They found that participants who reported intake of hot black tea and citrus peel had a significant reduction in the risk of squamous cell carcinoma. Further, they concluded that hot black tea and citrus peel displayed independent potential protection against SCC.11
Two years earlier, Zhao et al. used cultured keratinocytes and mouse and human skin to evaluate the effect of both orally and topically administered standardized black tea extract and its two major polyphenolic subfractions against UVB-induced photodamage. Topical pretreatment with the extract on SKH-1 hairless mice significantly lowered the incidence and severity of erythema and diminished skinfold thickness, compared with UVB-exposed nontreated mice. The black tea extract was similarly effective in human subjects. UVB-induced inflammation in murine as well as human skin also was reduced when the standardized extract was administered 5 minutes after UVB exposure. The investigators suggested that their findings indicated that black tea extracts have the capacity to mitigate UVB-generated erythema in human and murine skin.12
In 2011, George et al. assessed the chemopreventive effects of topical resveratrol and oral black tea polyphenols in blocking skin carcinogenesis in a two-stage mouse model initiated and promoted by DMBA and TPA, respectively. The combined treatment was found to reduce tumor incidence by approximately 89% (resveratrol alone, approximately 67%; black tea polyphenols alone, approximately 75%). Tumor volume and number also were significantly diminished by the synergistic combination, which, histologically, was noted for suppressing cellular proliferation and inducing apoptosis. The investigators concluded that oral black tea polyphenols combined with topical resveratrol exert greater chemopreventive activity than either compound alone and warrant study in trials for treating skin and other cancers.13
Animal studies on topical application
In 1997, Katiyar et al. investigated the anti-inflammatory effects of topically applied black tea polyphenols, primarily theaflavin gallates and (-)-epigallocatechin-3-gallate (EGCG), against TPA-induced inflammatory responses in murine skin. Significant inhibition against TPA-promoted induction of epidermal edema, hyperplasia, leukocyte infiltration, and proinflammatory cytokine expression was rendered by the preapplication of black tea polyphenols prior to TPA exposure. The investigators concluded that black tea polyphenols may be effective against human cutaneous inflammatory responses.14
Just over a decade later, Patel et al. investigated the in vivo antitumor-promoting effects of the most plentiful polymeric black tea polyphenols (thearubigins) in mice exposed to tumor-initiating DMBA and tumor-promoting TPA over a 40-week period. Pretreatment with topical thearubigins resulted in antipromoting effects in terms of latency, multiplicity, and incidence of skin papillomas. The black tea polyphenols also were found to reduce TPA-induced cell proliferation and epidermal cell apoptosis. The researchers attributed the protective effects of these compounds to their inhibitory impact on TPA-induced cellular proliferation.15
In 2011, Choi and Kim assessed the whitening effect of black tea water extract topically applied twice daily (6 days a week for 4 weeks) to UVB-induced hyperpigmented spots on the backs of brown guinea pigs. Treatment was divided into control (UVB and saline), vehicle control (UVB, propylene glycol, ethanol, and water), positive control (UVB and 2% hydroquinone), and two experimental groups (UVB and 1% black tea; UVB and 2% black tea). The investigators observed that the hyperpigmented spots treated with hydroquinone and black tea were clearly lighter than those treated by the control or vehicle-control groups. Histologic examination revealed that melanin pigmentation, melanocyte proliferation, and melanin production were significantly diminished in the groups treated with hydroquinone and both concentrations of black tea. The authors concluded that black tea suppresses melanocyte proliferation and melanosome synthesis in vivo, thus displaying the capacity to whiten skin in brown guinea pigs.16
In 2013, Yeh et al. found in nude mouse skin in vitro that niosomes appear to be feasible as a delivery vehicle for the dermal administration of black tea extracts as a sunscreen agent.1
Topical studies in humans
Building on findings 3 years earlier18, Türkoglu et al., in 2010, assessed the photoprotective effects of dermal gels produced from green and black tea aqueous extracts tested in vivo in the forearms of six volunteers exposed to artificial UV light (200-400 nm). In addition to the green tea and black tea gels, a 0.3% caffeine gel, a carbomer gel base, and a control were tested. The investigators reported no eruptions of UV-induced erythema in any of the black and green tea gel sites, but erythema was present to varying degrees at the areas treated with caffeine gel, carbomer gel, and control. The investigators concluded that the black and green tea extracts exhibited potent UV absorbance and that the formulated gels were effective in protecting the skin against UV-induced erythema. Further, the investigators suggested that these agents have the potential to protect against other harm caused by UV radiation, including photoaging.19
Conclusion
Though not as widely investigated as green tea, the therapeutic potential of black tea is of great interest. Although an abundance of laboratory evidence has emerged, clinical evidence is sparse. Nevertheless, laboratory data suggest the potential uses of black tea in the dermatologic realm and justify more human trials.
References
1. Cancer Lett. 1997 Mar 19;114(1-2):315-7.
2. Dermatol. Surg. 2005;31(7 Pt 2):873-80.
3. Oxid Med Cell Longev. 2012:2012:560682.
4. J Environ Pathol Toxicol Oncol. 2010;29(1):55-68.
5. Mol Carcinog. 2000 Jul;28(3):148-55.
6. Am J Clin Dermatol. 2010;11(4):247-67.
7. Carcinogenesis. 2008 Jan;29(1):129-38.
8. Cancer Res. 1994 Jul 1;54(13):3428-35.
9. Carcinogenesis. 1997 Nov;18(11):2163-9.
10. Mutat Res. 1998 Nov 9;422(1):191-9.
12. Photochem Photobiol. 1999 Oct;70(4):637-44.
13. PLoS One. 2011;6(8):e23395.
14. Carcinogenesis. 1997 Oct;18(10):1911-6.
15. Cell Prolif. 2008 Jun;41(3):532-53.
16. Toxicol Res. 2011 Sep;27(3):153-60.
17. Int J Dermatol. 2013 Feb;52(2):239-45.
18. Int J Cosmet Sci. 2007 Dec;29(6):437-42.
19. Drug Discov Ther. 2010 Oct;4(5):362-7.
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.
Naringenin
The flavanone naringenin (5,7,4-trihydroxyflavanone) is known to exhibit anticarcinogenic, antioxidative, antiatherogenic, estrogenic, and immunomodulatory activity (Nutr. Cancer. 2012;64:714-24; J. Nutr. 2001;131:235-41; Life Sci. 2013;93:516-24). Naringenin can be found in high concentrations in grapefruits, oranges, and other citrus fruits as well as tomatoes (skin), with grapefruit juice found to yield much higher levels in plasma than orange juice (J. Nutr. 2001;131:235-41; Am. J. Physiol. Gastrointest. Liver Physiol. 2000;279:G1148-54; Nutr. Cancer 2012;64:714-24). Naringenin has been shown, along with other flavanones such as hesperetin and ponciretin, to strongly inhibit IgE-induced beta-hexosaminidase release from RBL-2H3 cells. Sung-Hwan Park and associates have suggested that the glycosides of these substances have potential as agents for treating IgE-induced atopic allergies (Planta Med. 2005;71:24-7).
In 2012, Kushi Anand and associates also showed that the combination of curcumin and naringenin exerted antiangiogenic and antitumor effects in Swiss albino mice, adding that neither compound has been associated with reports of toxicity in animals or humans (Nutr. Cancer 2012;64:714-24).
Potential cutaneous benefits
Tae-Ho Kim and colleagues studied the effects of naringenin on 2,4-dinitrofluorobenzene (DNFB)-induced atomic dermatitis in NC/Nga mice in 2013. After repetitive skin contact with DNFB, mice received intraperitoneal injections of naringenin for 1 week, with the treatment with the fruit flavonoid significantly diminishing ear swelling and back skin lesions. The flavonoid also significantly inhibited interferon (IFN)-alpha production by activated CD4+ T cells and lowered serum IgE levels as well as DNFB-induced infiltration of eosinophils, mast cells, CD4+ T cells, and CD8+ T cells in skin lesions (Life Sci. 2013;93:516-24).
Also that year, a naringenin glucoside (naringenin-7-O-glucoside) was found in an industrial blanch water extract, a byproduct of almond processing, and believed to play a role in exerting or contributing to a photoprotective effect in a small in vivo study with 12 volunteers (Molecules 2013;18:12426-40).
In 2014, K. Murata and associates screened several Prunus species in a search for skin-whitening compounds. Using an antityrosinase assay, the investigators determined that P. persica exhibited the greatest inhibitory activity and, in additional evaluation, it was found to hinder melanogenesis in B16 rat melanoma cells. Further, they identified afzelin (3-O-alpha-L-rhamnosylkaempferol) and the flavanone naringenin as the active ingredients responsible for inhibition of tyrosinase and melanogenesis and concluded that these substances warrant attention as potential skin-whitening agents (Nat. Prod. Commun. 2014;9:185-8).
A 2014 study in the ophthalmologic literature may also shed light on the photoprotective properties of naringenin. Jun-Li Lin and colleagues, studying the effects of the flavanone in eye drops used to treat N-methyl-N-nitrosourea (MNU)-induced photoreceptor cell death in rats, found that topical naringenin dose-dependently shielded the outer nuclear layer, outer retina, and whole retina, and prevented structural and functional damages to retinal neurons (Int. J. Ophthalmol. 2014;7:391-6).
Conclusion
The antioxidative, antiatherogenic, anticarcinogenic, antiproliferative, antimutagenic, estrogenic, and immunomodulatory properties of naringenin have been established in the laboratory. It remains to be seen whether such activity can be harnessed for medical applications, particularly in the dermatologic arena. Nevertheless, this flavanone warrants watching as research into its potential cutaneous applications proceeds. Currently, there is a dearth of research, though, regarding the use of naringenin in topical products.
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.
The flavanone naringenin (5,7,4-trihydroxyflavanone) is known to exhibit anticarcinogenic, antioxidative, antiatherogenic, estrogenic, and immunomodulatory activity (Nutr. Cancer. 2012;64:714-24; J. Nutr. 2001;131:235-41; Life Sci. 2013;93:516-24). Naringenin can be found in high concentrations in grapefruits, oranges, and other citrus fruits as well as tomatoes (skin), with grapefruit juice found to yield much higher levels in plasma than orange juice (J. Nutr. 2001;131:235-41; Am. J. Physiol. Gastrointest. Liver Physiol. 2000;279:G1148-54; Nutr. Cancer 2012;64:714-24). Naringenin has been shown, along with other flavanones such as hesperetin and ponciretin, to strongly inhibit IgE-induced beta-hexosaminidase release from RBL-2H3 cells. Sung-Hwan Park and associates have suggested that the glycosides of these substances have potential as agents for treating IgE-induced atopic allergies (Planta Med. 2005;71:24-7).
In 2012, Kushi Anand and associates also showed that the combination of curcumin and naringenin exerted antiangiogenic and antitumor effects in Swiss albino mice, adding that neither compound has been associated with reports of toxicity in animals or humans (Nutr. Cancer 2012;64:714-24).
Potential cutaneous benefits
Tae-Ho Kim and colleagues studied the effects of naringenin on 2,4-dinitrofluorobenzene (DNFB)-induced atomic dermatitis in NC/Nga mice in 2013. After repetitive skin contact with DNFB, mice received intraperitoneal injections of naringenin for 1 week, with the treatment with the fruit flavonoid significantly diminishing ear swelling and back skin lesions. The flavonoid also significantly inhibited interferon (IFN)-alpha production by activated CD4+ T cells and lowered serum IgE levels as well as DNFB-induced infiltration of eosinophils, mast cells, CD4+ T cells, and CD8+ T cells in skin lesions (Life Sci. 2013;93:516-24).
Also that year, a naringenin glucoside (naringenin-7-O-glucoside) was found in an industrial blanch water extract, a byproduct of almond processing, and believed to play a role in exerting or contributing to a photoprotective effect in a small in vivo study with 12 volunteers (Molecules 2013;18:12426-40).
In 2014, K. Murata and associates screened several Prunus species in a search for skin-whitening compounds. Using an antityrosinase assay, the investigators determined that P. persica exhibited the greatest inhibitory activity and, in additional evaluation, it was found to hinder melanogenesis in B16 rat melanoma cells. Further, they identified afzelin (3-O-alpha-L-rhamnosylkaempferol) and the flavanone naringenin as the active ingredients responsible for inhibition of tyrosinase and melanogenesis and concluded that these substances warrant attention as potential skin-whitening agents (Nat. Prod. Commun. 2014;9:185-8).
A 2014 study in the ophthalmologic literature may also shed light on the photoprotective properties of naringenin. Jun-Li Lin and colleagues, studying the effects of the flavanone in eye drops used to treat N-methyl-N-nitrosourea (MNU)-induced photoreceptor cell death in rats, found that topical naringenin dose-dependently shielded the outer nuclear layer, outer retina, and whole retina, and prevented structural and functional damages to retinal neurons (Int. J. Ophthalmol. 2014;7:391-6).
Conclusion
The antioxidative, antiatherogenic, anticarcinogenic, antiproliferative, antimutagenic, estrogenic, and immunomodulatory properties of naringenin have been established in the laboratory. It remains to be seen whether such activity can be harnessed for medical applications, particularly in the dermatologic arena. Nevertheless, this flavanone warrants watching as research into its potential cutaneous applications proceeds. Currently, there is a dearth of research, though, regarding the use of naringenin in topical products.
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.
The flavanone naringenin (5,7,4-trihydroxyflavanone) is known to exhibit anticarcinogenic, antioxidative, antiatherogenic, estrogenic, and immunomodulatory activity (Nutr. Cancer. 2012;64:714-24; J. Nutr. 2001;131:235-41; Life Sci. 2013;93:516-24). Naringenin can be found in high concentrations in grapefruits, oranges, and other citrus fruits as well as tomatoes (skin), with grapefruit juice found to yield much higher levels in plasma than orange juice (J. Nutr. 2001;131:235-41; Am. J. Physiol. Gastrointest. Liver Physiol. 2000;279:G1148-54; Nutr. Cancer 2012;64:714-24). Naringenin has been shown, along with other flavanones such as hesperetin and ponciretin, to strongly inhibit IgE-induced beta-hexosaminidase release from RBL-2H3 cells. Sung-Hwan Park and associates have suggested that the glycosides of these substances have potential as agents for treating IgE-induced atopic allergies (Planta Med. 2005;71:24-7).
In 2012, Kushi Anand and associates also showed that the combination of curcumin and naringenin exerted antiangiogenic and antitumor effects in Swiss albino mice, adding that neither compound has been associated with reports of toxicity in animals or humans (Nutr. Cancer 2012;64:714-24).
Potential cutaneous benefits
Tae-Ho Kim and colleagues studied the effects of naringenin on 2,4-dinitrofluorobenzene (DNFB)-induced atomic dermatitis in NC/Nga mice in 2013. After repetitive skin contact with DNFB, mice received intraperitoneal injections of naringenin for 1 week, with the treatment with the fruit flavonoid significantly diminishing ear swelling and back skin lesions. The flavonoid also significantly inhibited interferon (IFN)-alpha production by activated CD4+ T cells and lowered serum IgE levels as well as DNFB-induced infiltration of eosinophils, mast cells, CD4+ T cells, and CD8+ T cells in skin lesions (Life Sci. 2013;93:516-24).
Also that year, a naringenin glucoside (naringenin-7-O-glucoside) was found in an industrial blanch water extract, a byproduct of almond processing, and believed to play a role in exerting or contributing to a photoprotective effect in a small in vivo study with 12 volunteers (Molecules 2013;18:12426-40).
In 2014, K. Murata and associates screened several Prunus species in a search for skin-whitening compounds. Using an antityrosinase assay, the investigators determined that P. persica exhibited the greatest inhibitory activity and, in additional evaluation, it was found to hinder melanogenesis in B16 rat melanoma cells. Further, they identified afzelin (3-O-alpha-L-rhamnosylkaempferol) and the flavanone naringenin as the active ingredients responsible for inhibition of tyrosinase and melanogenesis and concluded that these substances warrant attention as potential skin-whitening agents (Nat. Prod. Commun. 2014;9:185-8).
A 2014 study in the ophthalmologic literature may also shed light on the photoprotective properties of naringenin. Jun-Li Lin and colleagues, studying the effects of the flavanone in eye drops used to treat N-methyl-N-nitrosourea (MNU)-induced photoreceptor cell death in rats, found that topical naringenin dose-dependently shielded the outer nuclear layer, outer retina, and whole retina, and prevented structural and functional damages to retinal neurons (Int. J. Ophthalmol. 2014;7:391-6).
Conclusion
The antioxidative, antiatherogenic, anticarcinogenic, antiproliferative, antimutagenic, estrogenic, and immunomodulatory properties of naringenin have been established in the laboratory. It remains to be seen whether such activity can be harnessed for medical applications, particularly in the dermatologic arena. Nevertheless, this flavanone warrants watching as research into its potential cutaneous applications proceeds. Currently, there is a dearth of research, though, regarding the use of naringenin in topical products.
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.
Why your patients should buy skincare products from you
The Internet has changed many facets of modern life, and the practice of medicine has not gone untouched. Consider, for better or worse, the reliance of many patients on WebMD and various other sites for self-diagnosis before consulting with a physician. Even before the Internet, patients would self-diagnose their skin type (more than 80% of them get it wrong). The Internet allows them access to most cosmeceutical brands, the misuse of which leads to unintended consequences that can affect skin health. Clearly, patients who receive advice from a trained medical professional have better outcomes. One reason for this is that the doctor (or aesthetician) spends time with the patient, explaining what products to use and in which order to use them, and follows up with the patient to assess the outcome and adjust the regimen as needed. The problem arises when these patients decide to purchase the products from a source other than their treating physician. Only about 30% of patients buy refills from their doctor for second purchases, and just 15% purchase products from their doctor the third time around. Why is this? It is likely the convenience and the low cost that drive patients to purchase from sources other than their physician or aesthetician. This desire to save money carries significant risks. Many the products online are expired or counterfeit, or are old containers refilled with a different formulation. Patients should be cautioned to only buy products from a source they trust.
I have had dozens of patients bringing in counterfeit products in the last few months. It seems that the problem is becoming more common. I interviewed several companies about this to see whether others were experiencing the same trend. This is what I found:
Some companies report that they have seen their samples and trade size containers being sold on eBay. Joe Ragosta of Topix Pharmaceuticals reports that when his company has asked such sellers if they are obtaining these products – marked as samples – from the company, they hear a range of defensive responses, including: “I got it at a show” or “My doctor gave me samples, and I decided to sell them” and “I work at a doctor’s office, and they let me take products as needed.” Make sure that no one on your staff is taking samples and selling them online.
One example: NeoStrata is concerned about the fraudulent use of their products. They recommend that patients purchase their products only from a known physician, ideally from the physician’s office rather than the website. The company understands that customers may want to save money wherever they can and might prefer to buy products online. NeoStrata urges customers who opt to buy online to make such purchases through physician-affiliated websites, where the doctor is clearly identified. At the very least, the company urges patients to choose only sites where they can contact someone and obtain the name of a physician. Further, they strongly discourage using eBay or other auction sites, which do not vouch for the safety and authenticity of products sold through their services.
Other potential problems with skin care products sold online include the following.
Counterfeit products
Several reports have indicated that counterfeit skin products originating in other countries have made their way into the United States and, according to the article published on the website Fact Based Skin Care, pharmaceuticals and personal care products, including cosmetics, are among the top five types of products seized by U.S. Customs and Border Patrol agents (Coy, C. Dangers of Counterfeit Cosmetics, Aug. 4, 2014). Such products include old bottles refilled with inexpensive imitation creams or bottles made to look like legitimate products that in fact contain imitation creams. I once had a patient present with an adverse reaction to a retinol product, which she brought with her to the visit. I sent the bottle to the company, which confirmed my suspicion that the product was counterfeit – a different bottle with a similar label.
In February 2014, CBS New York ran a segment on the potential inclusion of carcinogenic and other harmful ingredients found in online personal care products touted for their low prices (CBS New York. Counterfeit Cosmetics May Be Harmful To Your Health. Feb. 27, 2014). Not even 2 weeks later, CNN reported on the arrest of two brothers in New York alleged to have masterminded a multimillion-dollar counterfeit health and beauty product ring (CNN. Zulueta A. Massive Fake Health and Beauty Supplies Ring Busted. March 9, 2014). ABC’s Good Morning America followed suit with a segment in April 2014 that exposed aspects of the use of knock-off cosmetic products (ABC News, Good Morning America. Online Beauty Bargains: Is It the Real Deal? April 3, 2014).
The Federal Bureau of Investigation has posted memos concerning counterfeit and potentially compromised and hazardous cosmetics and fragrances, offering tips aimed at readily identifying or avoiding unauthorized products.
Torie Hardee of EltaMD summarized that counterfeit products can sometimes be identified by lack of an expiration date on the bottle, discoloration or slightly different fonts on bottles and packaging, and the manufacturer’s address on the bottle.
Jan Marini Company representative Stuart Mohr noted that their company has received returns of products that they had not manufactured, as well as their own current or discontinued products returned years after the expiration date. The Jan Marini Co., and most other companies, will not guarantee any product purchased via nonauthorized resellers, because the authenticity and safety of such products cannot be verified.
“These unauthorized resellers are sophisticated, often even working in rings, and find it easy to hide their real identity,” said Mr. Mohr. “Addresses are often hidden or vague; emails are not linked to any specific person; and it’s easy to use false names. If a person is caught in an unauthorized online transaction, it’s easy to change the email address or name and start again,” he added.
FBI’s tips for spotting counterfeit cosmetics and fragrances
• The product is a sample size.
• The packaging differs slightly from the authentic brand (different color or font).
• The product’s wrapping appears haphazard.
• The product is being advertised as a “limited edition” even though the authentic manufacturer doesn’t offer it as a limited edition.
• The product is not listed on the manufacturer’s website.
• The price is drastically lower than the MSRP.
• The product’s consistency or texture doesn’t feel or look like the authentic brand.
• For fragrances, something seems off about the scent, and the color of the fluid in the bottle might be different than the original.
• They are being sold at nonauthorized retailers, including flea markets and discount stores.
• The label does not contain lot number, bar code, manufacturer’s address, or expiration date.
Expired products
Unscrupulous online retailers may slash prices on expired products and remove the expiration date from the package. In my practice, a patient experiencing an erythematous reaction brought in the “SkinMedica” product bottle, which looked suspicious to me. The packaging that the product was in had been discontinued 8 years earlier. It is important to remember that ingredients, particularly retinol, degrade with exposure to air, sun, and heat, and over time. This is most likely what caused my patient’s adverse reaction, and her initial savings from the product caused her several weeks of irritated skin.
Diverted products
SkinMedica reports that diverted products are a trickier issue than counterfeit products, because their packaging and formulas are sufficiently complex to make counterfeiting too difficult to be profitable. Instead, their products have been sold on the so-called gray market below the manufacturer suggested retail price (MSRP), typically online. In these cases, the company cannot help patients with returns or complaints because they cannot verify the chain of custody of the purchased product. They are addressing this problem, though, with an awareness campaign called “Authentic and Authorized.” Its goal is to alert patients and the physicians who dispense their products of the benefits of a physician-dispensed model of skin care, with best outcomes achieved when doctors are prescribing a skin care regimen. SkinMedica emphasizes that no website can guarantee outcomes comparable to a skin care professional and product quality and safety can only be enforced when dispensed through authorized channels.
Potentially illegal or toxic ingredients
Several products that have entered the United States marketed as skin lighteners, antiaging agents, and acne treatment products have been found to contain mercury, according to a consumer update from the FDA. Arsenic, lead, beryllium, and other harmful toxins as well as allergy-inducing fragrances or preservatives not approved as safe in the U.S. may also be found in such products of dubious origin.
Improper storage
Products purveyed online are often stored in hot warehouses. As mentioned above, heat degrades and alters ingredients, rendering compounds such as retinol, benzoyl peroxide, peptides, and ascorbic acid worthless. Extreme cold can also damage the chemical integrity of products. Notably, organic products are more vulnerable because they lack preservatives to gird them against temperature variations and microbes that grow in hot, damp environments.
Lookalike imposters
Generic formulations are packaged to piggyback onto the success of well-known products. Such products found in drugstores may be packaged to look like Cetaphil or Aveeno items, but cost less, and deliver less. While the ingredients on the copycats are identical to those found in the branded preparations, the order in which ingredients are added, the temperature, pH, and even when and how fast ingredients are stirred are part of the proprietary recipe of the company and play a significant role in the potential of the end product and the actions the product exerts on the skin.
Conclusion
Whether or not you sell skin care products in your office, there is much you can do to educate your patients about skin care product safety. Namely, the farther a consumer gets from the source of the product or from reliable endorsers of products, the greater the opportunity for encountering fraudulent or counterfeit products. Patients are best served by sources they can trust, such as their dermatologist. If you sell products in your office, encourage your patients to buy refills from you so they can be assured of the proper formulations. Finally, encourage your patients not to skimp when it comes to the health of their skin, reminding them that it may cost them much more in terms of time, skin irritation, improper treatment, and all related expenses to buy products cheaply from unreliable sources.
Give your patients a copy of this article so that they will understand the enormity of the problem.
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.
The Internet has changed many facets of modern life, and the practice of medicine has not gone untouched. Consider, for better or worse, the reliance of many patients on WebMD and various other sites for self-diagnosis before consulting with a physician. Even before the Internet, patients would self-diagnose their skin type (more than 80% of them get it wrong). The Internet allows them access to most cosmeceutical brands, the misuse of which leads to unintended consequences that can affect skin health. Clearly, patients who receive advice from a trained medical professional have better outcomes. One reason for this is that the doctor (or aesthetician) spends time with the patient, explaining what products to use and in which order to use them, and follows up with the patient to assess the outcome and adjust the regimen as needed. The problem arises when these patients decide to purchase the products from a source other than their treating physician. Only about 30% of patients buy refills from their doctor for second purchases, and just 15% purchase products from their doctor the third time around. Why is this? It is likely the convenience and the low cost that drive patients to purchase from sources other than their physician or aesthetician. This desire to save money carries significant risks. Many the products online are expired or counterfeit, or are old containers refilled with a different formulation. Patients should be cautioned to only buy products from a source they trust.
I have had dozens of patients bringing in counterfeit products in the last few months. It seems that the problem is becoming more common. I interviewed several companies about this to see whether others were experiencing the same trend. This is what I found:
Some companies report that they have seen their samples and trade size containers being sold on eBay. Joe Ragosta of Topix Pharmaceuticals reports that when his company has asked such sellers if they are obtaining these products – marked as samples – from the company, they hear a range of defensive responses, including: “I got it at a show” or “My doctor gave me samples, and I decided to sell them” and “I work at a doctor’s office, and they let me take products as needed.” Make sure that no one on your staff is taking samples and selling them online.
One example: NeoStrata is concerned about the fraudulent use of their products. They recommend that patients purchase their products only from a known physician, ideally from the physician’s office rather than the website. The company understands that customers may want to save money wherever they can and might prefer to buy products online. NeoStrata urges customers who opt to buy online to make such purchases through physician-affiliated websites, where the doctor is clearly identified. At the very least, the company urges patients to choose only sites where they can contact someone and obtain the name of a physician. Further, they strongly discourage using eBay or other auction sites, which do not vouch for the safety and authenticity of products sold through their services.
Other potential problems with skin care products sold online include the following.
Counterfeit products
Several reports have indicated that counterfeit skin products originating in other countries have made their way into the United States and, according to the article published on the website Fact Based Skin Care, pharmaceuticals and personal care products, including cosmetics, are among the top five types of products seized by U.S. Customs and Border Patrol agents (Coy, C. Dangers of Counterfeit Cosmetics, Aug. 4, 2014). Such products include old bottles refilled with inexpensive imitation creams or bottles made to look like legitimate products that in fact contain imitation creams. I once had a patient present with an adverse reaction to a retinol product, which she brought with her to the visit. I sent the bottle to the company, which confirmed my suspicion that the product was counterfeit – a different bottle with a similar label.
In February 2014, CBS New York ran a segment on the potential inclusion of carcinogenic and other harmful ingredients found in online personal care products touted for their low prices (CBS New York. Counterfeit Cosmetics May Be Harmful To Your Health. Feb. 27, 2014). Not even 2 weeks later, CNN reported on the arrest of two brothers in New York alleged to have masterminded a multimillion-dollar counterfeit health and beauty product ring (CNN. Zulueta A. Massive Fake Health and Beauty Supplies Ring Busted. March 9, 2014). ABC’s Good Morning America followed suit with a segment in April 2014 that exposed aspects of the use of knock-off cosmetic products (ABC News, Good Morning America. Online Beauty Bargains: Is It the Real Deal? April 3, 2014).
The Federal Bureau of Investigation has posted memos concerning counterfeit and potentially compromised and hazardous cosmetics and fragrances, offering tips aimed at readily identifying or avoiding unauthorized products.
Torie Hardee of EltaMD summarized that counterfeit products can sometimes be identified by lack of an expiration date on the bottle, discoloration or slightly different fonts on bottles and packaging, and the manufacturer’s address on the bottle.
Jan Marini Company representative Stuart Mohr noted that their company has received returns of products that they had not manufactured, as well as their own current or discontinued products returned years after the expiration date. The Jan Marini Co., and most other companies, will not guarantee any product purchased via nonauthorized resellers, because the authenticity and safety of such products cannot be verified.
“These unauthorized resellers are sophisticated, often even working in rings, and find it easy to hide their real identity,” said Mr. Mohr. “Addresses are often hidden or vague; emails are not linked to any specific person; and it’s easy to use false names. If a person is caught in an unauthorized online transaction, it’s easy to change the email address or name and start again,” he added.
FBI’s tips for spotting counterfeit cosmetics and fragrances
• The product is a sample size.
• The packaging differs slightly from the authentic brand (different color or font).
• The product’s wrapping appears haphazard.
• The product is being advertised as a “limited edition” even though the authentic manufacturer doesn’t offer it as a limited edition.
• The product is not listed on the manufacturer’s website.
• The price is drastically lower than the MSRP.
• The product’s consistency or texture doesn’t feel or look like the authentic brand.
• For fragrances, something seems off about the scent, and the color of the fluid in the bottle might be different than the original.
• They are being sold at nonauthorized retailers, including flea markets and discount stores.
• The label does not contain lot number, bar code, manufacturer’s address, or expiration date.
Expired products
Unscrupulous online retailers may slash prices on expired products and remove the expiration date from the package. In my practice, a patient experiencing an erythematous reaction brought in the “SkinMedica” product bottle, which looked suspicious to me. The packaging that the product was in had been discontinued 8 years earlier. It is important to remember that ingredients, particularly retinol, degrade with exposure to air, sun, and heat, and over time. This is most likely what caused my patient’s adverse reaction, and her initial savings from the product caused her several weeks of irritated skin.
Diverted products
SkinMedica reports that diverted products are a trickier issue than counterfeit products, because their packaging and formulas are sufficiently complex to make counterfeiting too difficult to be profitable. Instead, their products have been sold on the so-called gray market below the manufacturer suggested retail price (MSRP), typically online. In these cases, the company cannot help patients with returns or complaints because they cannot verify the chain of custody of the purchased product. They are addressing this problem, though, with an awareness campaign called “Authentic and Authorized.” Its goal is to alert patients and the physicians who dispense their products of the benefits of a physician-dispensed model of skin care, with best outcomes achieved when doctors are prescribing a skin care regimen. SkinMedica emphasizes that no website can guarantee outcomes comparable to a skin care professional and product quality and safety can only be enforced when dispensed through authorized channels.
Potentially illegal or toxic ingredients
Several products that have entered the United States marketed as skin lighteners, antiaging agents, and acne treatment products have been found to contain mercury, according to a consumer update from the FDA. Arsenic, lead, beryllium, and other harmful toxins as well as allergy-inducing fragrances or preservatives not approved as safe in the U.S. may also be found in such products of dubious origin.
Improper storage
Products purveyed online are often stored in hot warehouses. As mentioned above, heat degrades and alters ingredients, rendering compounds such as retinol, benzoyl peroxide, peptides, and ascorbic acid worthless. Extreme cold can also damage the chemical integrity of products. Notably, organic products are more vulnerable because they lack preservatives to gird them against temperature variations and microbes that grow in hot, damp environments.
Lookalike imposters
Generic formulations are packaged to piggyback onto the success of well-known products. Such products found in drugstores may be packaged to look like Cetaphil or Aveeno items, but cost less, and deliver less. While the ingredients on the copycats are identical to those found in the branded preparations, the order in which ingredients are added, the temperature, pH, and even when and how fast ingredients are stirred are part of the proprietary recipe of the company and play a significant role in the potential of the end product and the actions the product exerts on the skin.
Conclusion
Whether or not you sell skin care products in your office, there is much you can do to educate your patients about skin care product safety. Namely, the farther a consumer gets from the source of the product or from reliable endorsers of products, the greater the opportunity for encountering fraudulent or counterfeit products. Patients are best served by sources they can trust, such as their dermatologist. If you sell products in your office, encourage your patients to buy refills from you so they can be assured of the proper formulations. Finally, encourage your patients not to skimp when it comes to the health of their skin, reminding them that it may cost them much more in terms of time, skin irritation, improper treatment, and all related expenses to buy products cheaply from unreliable sources.
Give your patients a copy of this article so that they will understand the enormity of the problem.
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.
The Internet has changed many facets of modern life, and the practice of medicine has not gone untouched. Consider, for better or worse, the reliance of many patients on WebMD and various other sites for self-diagnosis before consulting with a physician. Even before the Internet, patients would self-diagnose their skin type (more than 80% of them get it wrong). The Internet allows them access to most cosmeceutical brands, the misuse of which leads to unintended consequences that can affect skin health. Clearly, patients who receive advice from a trained medical professional have better outcomes. One reason for this is that the doctor (or aesthetician) spends time with the patient, explaining what products to use and in which order to use them, and follows up with the patient to assess the outcome and adjust the regimen as needed. The problem arises when these patients decide to purchase the products from a source other than their treating physician. Only about 30% of patients buy refills from their doctor for second purchases, and just 15% purchase products from their doctor the third time around. Why is this? It is likely the convenience and the low cost that drive patients to purchase from sources other than their physician or aesthetician. This desire to save money carries significant risks. Many the products online are expired or counterfeit, or are old containers refilled with a different formulation. Patients should be cautioned to only buy products from a source they trust.
I have had dozens of patients bringing in counterfeit products in the last few months. It seems that the problem is becoming more common. I interviewed several companies about this to see whether others were experiencing the same trend. This is what I found:
Some companies report that they have seen their samples and trade size containers being sold on eBay. Joe Ragosta of Topix Pharmaceuticals reports that when his company has asked such sellers if they are obtaining these products – marked as samples – from the company, they hear a range of defensive responses, including: “I got it at a show” or “My doctor gave me samples, and I decided to sell them” and “I work at a doctor’s office, and they let me take products as needed.” Make sure that no one on your staff is taking samples and selling them online.
One example: NeoStrata is concerned about the fraudulent use of their products. They recommend that patients purchase their products only from a known physician, ideally from the physician’s office rather than the website. The company understands that customers may want to save money wherever they can and might prefer to buy products online. NeoStrata urges customers who opt to buy online to make such purchases through physician-affiliated websites, where the doctor is clearly identified. At the very least, the company urges patients to choose only sites where they can contact someone and obtain the name of a physician. Further, they strongly discourage using eBay or other auction sites, which do not vouch for the safety and authenticity of products sold through their services.
Other potential problems with skin care products sold online include the following.
Counterfeit products
Several reports have indicated that counterfeit skin products originating in other countries have made their way into the United States and, according to the article published on the website Fact Based Skin Care, pharmaceuticals and personal care products, including cosmetics, are among the top five types of products seized by U.S. Customs and Border Patrol agents (Coy, C. Dangers of Counterfeit Cosmetics, Aug. 4, 2014). Such products include old bottles refilled with inexpensive imitation creams or bottles made to look like legitimate products that in fact contain imitation creams. I once had a patient present with an adverse reaction to a retinol product, which she brought with her to the visit. I sent the bottle to the company, which confirmed my suspicion that the product was counterfeit – a different bottle with a similar label.
In February 2014, CBS New York ran a segment on the potential inclusion of carcinogenic and other harmful ingredients found in online personal care products touted for their low prices (CBS New York. Counterfeit Cosmetics May Be Harmful To Your Health. Feb. 27, 2014). Not even 2 weeks later, CNN reported on the arrest of two brothers in New York alleged to have masterminded a multimillion-dollar counterfeit health and beauty product ring (CNN. Zulueta A. Massive Fake Health and Beauty Supplies Ring Busted. March 9, 2014). ABC’s Good Morning America followed suit with a segment in April 2014 that exposed aspects of the use of knock-off cosmetic products (ABC News, Good Morning America. Online Beauty Bargains: Is It the Real Deal? April 3, 2014).
The Federal Bureau of Investigation has posted memos concerning counterfeit and potentially compromised and hazardous cosmetics and fragrances, offering tips aimed at readily identifying or avoiding unauthorized products.
Torie Hardee of EltaMD summarized that counterfeit products can sometimes be identified by lack of an expiration date on the bottle, discoloration or slightly different fonts on bottles and packaging, and the manufacturer’s address on the bottle.
Jan Marini Company representative Stuart Mohr noted that their company has received returns of products that they had not manufactured, as well as their own current or discontinued products returned years after the expiration date. The Jan Marini Co., and most other companies, will not guarantee any product purchased via nonauthorized resellers, because the authenticity and safety of such products cannot be verified.
“These unauthorized resellers are sophisticated, often even working in rings, and find it easy to hide their real identity,” said Mr. Mohr. “Addresses are often hidden or vague; emails are not linked to any specific person; and it’s easy to use false names. If a person is caught in an unauthorized online transaction, it’s easy to change the email address or name and start again,” he added.
FBI’s tips for spotting counterfeit cosmetics and fragrances
• The product is a sample size.
• The packaging differs slightly from the authentic brand (different color or font).
• The product’s wrapping appears haphazard.
• The product is being advertised as a “limited edition” even though the authentic manufacturer doesn’t offer it as a limited edition.
• The product is not listed on the manufacturer’s website.
• The price is drastically lower than the MSRP.
• The product’s consistency or texture doesn’t feel or look like the authentic brand.
• For fragrances, something seems off about the scent, and the color of the fluid in the bottle might be different than the original.
• They are being sold at nonauthorized retailers, including flea markets and discount stores.
• The label does not contain lot number, bar code, manufacturer’s address, or expiration date.
Expired products
Unscrupulous online retailers may slash prices on expired products and remove the expiration date from the package. In my practice, a patient experiencing an erythematous reaction brought in the “SkinMedica” product bottle, which looked suspicious to me. The packaging that the product was in had been discontinued 8 years earlier. It is important to remember that ingredients, particularly retinol, degrade with exposure to air, sun, and heat, and over time. This is most likely what caused my patient’s adverse reaction, and her initial savings from the product caused her several weeks of irritated skin.
Diverted products
SkinMedica reports that diverted products are a trickier issue than counterfeit products, because their packaging and formulas are sufficiently complex to make counterfeiting too difficult to be profitable. Instead, their products have been sold on the so-called gray market below the manufacturer suggested retail price (MSRP), typically online. In these cases, the company cannot help patients with returns or complaints because they cannot verify the chain of custody of the purchased product. They are addressing this problem, though, with an awareness campaign called “Authentic and Authorized.” Its goal is to alert patients and the physicians who dispense their products of the benefits of a physician-dispensed model of skin care, with best outcomes achieved when doctors are prescribing a skin care regimen. SkinMedica emphasizes that no website can guarantee outcomes comparable to a skin care professional and product quality and safety can only be enforced when dispensed through authorized channels.
Potentially illegal or toxic ingredients
Several products that have entered the United States marketed as skin lighteners, antiaging agents, and acne treatment products have been found to contain mercury, according to a consumer update from the FDA. Arsenic, lead, beryllium, and other harmful toxins as well as allergy-inducing fragrances or preservatives not approved as safe in the U.S. may also be found in such products of dubious origin.
Improper storage
Products purveyed online are often stored in hot warehouses. As mentioned above, heat degrades and alters ingredients, rendering compounds such as retinol, benzoyl peroxide, peptides, and ascorbic acid worthless. Extreme cold can also damage the chemical integrity of products. Notably, organic products are more vulnerable because they lack preservatives to gird them against temperature variations and microbes that grow in hot, damp environments.
Lookalike imposters
Generic formulations are packaged to piggyback onto the success of well-known products. Such products found in drugstores may be packaged to look like Cetaphil or Aveeno items, but cost less, and deliver less. While the ingredients on the copycats are identical to those found in the branded preparations, the order in which ingredients are added, the temperature, pH, and even when and how fast ingredients are stirred are part of the proprietary recipe of the company and play a significant role in the potential of the end product and the actions the product exerts on the skin.
Conclusion
Whether or not you sell skin care products in your office, there is much you can do to educate your patients about skin care product safety. Namely, the farther a consumer gets from the source of the product or from reliable endorsers of products, the greater the opportunity for encountering fraudulent or counterfeit products. Patients are best served by sources they can trust, such as their dermatologist. If you sell products in your office, encourage your patients to buy refills from you so they can be assured of the proper formulations. Finally, encourage your patients not to skimp when it comes to the health of their skin, reminding them that it may cost them much more in terms of time, skin irritation, improper treatment, and all related expenses to buy products cheaply from unreliable sources.
Give your patients a copy of this article so that they will understand the enormity of the problem.
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.
