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Angelica: Part II
Besides Angelica sinensis, discussed last month, other species of Angelica have been studied for their medicinal potential, and, gradually, these species have been introduced into topical formulations.
Antitumor Activity
In a 2005 study, mice with highly metastatic drug-resistant tumors were used to test the effects of various herbal compounds on tumor growth and metastasis. Although the focus of the study was stilbene compounds, investigators found that two chalcone derivatives from Angelica keiskei roots inhibited tumor growth and metastasis. The chalcone derivatives worked by suppressing tumor-induced neovascularization and/or reducing the immune suppression brought on by tumors (In Vivo 2005;19:37–60).
Chalcone extracts of A. keiskei root, also known as ashitaba, which is consumed as a vegetable in Japan, also exhibited antitumorigenic activity in the two-phase mouse skin cancer model, in which carcinogenesis is induced by 7,12-dimethylbenz[a]anthracene (DMBA) and promoted by 12-O-tetradecanoylphorbol-13-acetate (TPA) (Planta Med. 1991;57:242–6).
In another study, xanthoangelol, a major chalcone constituent of A. keiskei, was found to dose-dependently decrease the survival rates of human neuroblastoma (IMR-32) and leukemia (Jurkat) cell lines. The findings indicated that the angelica component induced apoptosis by activating caspase-3 in neuroblastoma and leukemia cells without involving Bax/Bcl-2 proteins. The investigators concluded that xanthoangelol has potential as an agent against these cancers (Biol. Pharm. Bull. 2005;28:1404–7).
Other Angelica species besides keiskei and sinensis have shown antitumorigenic activity. Constituents of the Japanese drug shi-un-kou, which contains A. acutiloba, have been evaluated in assays. A. acutiloba alone and in combination with another constituent, Macrotomia euchroma, exhibited inhibitory effects, including reduced cytotoxicity, on Epstein-Barr virus activation induced by the tumor promoter TPA. The authors reported that a subsequent in vivo study in mice showed that shi-un-kou significantly inhibited skin tumor formation induced by TPA (Yakugaku Zasshi 1989;109:843–6).
In other research, investigators isolated the coumarin compound decursin from Korean angelica (A. gigantis, also known as A. gigas) root. They observed that decursin treatment for 24–96 hours strongly inhibited growth and dose-dependently induced apoptosis in human prostate carcinoma cells (Urol. Oncol. 2005;23:379–80).
In addition, another Angelica species, A. archangelica, exhibits antitumorigenic properties. Investigators evaluated the in vitro and in vivo effects of A. archangelica leaf extract on the growth of Crl mouse breast cancer cells. In vitro, the extract was found to be mildly antiproliferative. In the in vivo segment of the study, 11 of 20 mice were injected with A. archangelica leaf extract, and 9 of them developed no or small tumors, whereas control mice developed tumors that were significantly larger. The antitumor properties of A. archangelica extract could not be attributed to the antiproliferative characteristics of the furanocoumarins in the extract (In Vivo 2005;19:191–4).
Significant antiproliferative activity has also been identified in the tincture of A. archangelica, using the human pancreas cancer cell line PANC-1 as a model. Investigators ascribed most of the antiproliferative activity to imperatorin and xanthotoxin, the two furanocoumarins most prevalent in the A. archangelica tincture (Z. Naturforsch. [C] 2004;59:523–7).
Dermatologic Potential
In addition to antitumorigenic activity, several Angelica species have exhibited properties pertinent to clinical dermatology. Hwaotang, a traditional Korean formulation that combines seven herbs, including A. gigas, exerts anti-inflammatory effects related to the inhibition of human neutrophil functions and of nitric oxide and prostaglandin E2 production (Immunopharmacol. Immunotoxicol. 2004;26:53–73).
In a study of the anti-inflammatory activity of a new formulation containing Synurus deltoides and A. gigas extracts, along with glucosamine sulfate, the medication (SAG) dose dependently inhibited ear edema in mice induced by arachidonic acid and TPA. Prostaglandin E2 production associated with mouse skin lesions was also significantly reduced by SAG, as well as by treatment with S. deltoides extract alone. The authors acknowledged that although SAG is not as potent as anti-inflammatory products in widespread use, this A. gigas-containing preparation has potential benefits as a neutraceutical therapy for inflammatory conditions (Arch. Pharm. Res. 2005;28:848–53).
A study of herbs used in traditional Chinese and Japanese medicine to treat acne revealed that the ethanol extract (0.01%) of Angelica dahurica substantially inhibited neutrophil chemotaxis, at a level comparable to that of erythromycin (0.01%). In the same study, Rhizoma coptidis displayed a stronger antilipogenic effect than did retinoic acid (0.01%), and Glycyrrhiza glabra (licorice) showed significant antibacterial activity against P. acnes. These results led the researchers to conclude that a formulation containing all three herbs would have potential in the prevention and treatment of acne (Skin Pharmacol. Appl. Skin Physiol. 2003;16:84–90). A. dahurica, which also contains lactones and psoralen, and has been used traditionally to treat psoriasis and for its reputed antihistamine effects.
In a study evaluating extracts from 15 plants used in traditional Chinese medicine to treat topical inflammations, investigators focused on the inhibitory effects on enzymes that are therapeutic targets in cutaneous conditions, specifically 5-lipoxygenase, cyclooxygenase, and elastase. Four plant species, including A. dahurica and A. pubescens, inhibited elastase in intact leukocytes and platelets (J. Pharm. Pharmacol. 2003;55:1275–82; Planta Med. 1998;64:525–9). In addition, A. pubescens has been found to confer analgesic and anti-inflammatory effects (Planta Med. 1995;61:2–8). One of the main active components isolated from A. pubescens, osthole, a coumarin compound, has also been shown to exert a nonspecific relaxant effect on the trachea of guinea pigs (Naunyn Schmiedebergs Arch. Pharmacol. 1994;349:202–8).
At the Store
Zestra Feminine Arousal Fluid (Zestra Laboratories Inc.) is a topical botanical formulation containing A. archangelica along with borage seed oil, evening primrose oil, ascorbyl palmitate, and alpha tocopherol. The product is intended to enhance female sexual pleasure and arousal.
Investigators conducted a randomized, double-blind, crossover study to assess the efficacy and safety of Zestra in 10 women with and 10 women without female sexual arousal disorder. Using questionnaires, participants reported on a range of sexual functions pertaining to home use of the formulation. The results indicated statistically significant overall improvements in sexual function in both test groups, compared with placebo (J. Sex Marital Ther. 2003;29 [Suppl 1]:33–44).
Conclusions
A wide range of Angelica species possess properties found to be of medical, including dermatologic, benefit. In addition to A. sinensis (discussed in this column in August), A. archangelica, A. dahurica, and A. gigas have been used successfully in traditional herbal medicines, and research is ongoing on these and other species, including A. keiskei, A. pubescens, and A. acutiloba.
While the overall body of research is slim on the efficacy of these herbs, the extant evidence supports further investigation and provides reasons for optimism. In the meantime, as is typical in the case of myriad botanic ingredients, there are several unproven formulations available to consumers that contain botanical cocktails including the biologically active Angelica species.
Besides Angelica sinensis, discussed last month, other species of Angelica have been studied for their medicinal potential, and, gradually, these species have been introduced into topical formulations.
Antitumor Activity
In a 2005 study, mice with highly metastatic drug-resistant tumors were used to test the effects of various herbal compounds on tumor growth and metastasis. Although the focus of the study was stilbene compounds, investigators found that two chalcone derivatives from Angelica keiskei roots inhibited tumor growth and metastasis. The chalcone derivatives worked by suppressing tumor-induced neovascularization and/or reducing the immune suppression brought on by tumors (In Vivo 2005;19:37–60).
Chalcone extracts of A. keiskei root, also known as ashitaba, which is consumed as a vegetable in Japan, also exhibited antitumorigenic activity in the two-phase mouse skin cancer model, in which carcinogenesis is induced by 7,12-dimethylbenz[a]anthracene (DMBA) and promoted by 12-O-tetradecanoylphorbol-13-acetate (TPA) (Planta Med. 1991;57:242–6).
In another study, xanthoangelol, a major chalcone constituent of A. keiskei, was found to dose-dependently decrease the survival rates of human neuroblastoma (IMR-32) and leukemia (Jurkat) cell lines. The findings indicated that the angelica component induced apoptosis by activating caspase-3 in neuroblastoma and leukemia cells without involving Bax/Bcl-2 proteins. The investigators concluded that xanthoangelol has potential as an agent against these cancers (Biol. Pharm. Bull. 2005;28:1404–7).
Other Angelica species besides keiskei and sinensis have shown antitumorigenic activity. Constituents of the Japanese drug shi-un-kou, which contains A. acutiloba, have been evaluated in assays. A. acutiloba alone and in combination with another constituent, Macrotomia euchroma, exhibited inhibitory effects, including reduced cytotoxicity, on Epstein-Barr virus activation induced by the tumor promoter TPA. The authors reported that a subsequent in vivo study in mice showed that shi-un-kou significantly inhibited skin tumor formation induced by TPA (Yakugaku Zasshi 1989;109:843–6).
In other research, investigators isolated the coumarin compound decursin from Korean angelica (A. gigantis, also known as A. gigas) root. They observed that decursin treatment for 24–96 hours strongly inhibited growth and dose-dependently induced apoptosis in human prostate carcinoma cells (Urol. Oncol. 2005;23:379–80).
In addition, another Angelica species, A. archangelica, exhibits antitumorigenic properties. Investigators evaluated the in vitro and in vivo effects of A. archangelica leaf extract on the growth of Crl mouse breast cancer cells. In vitro, the extract was found to be mildly antiproliferative. In the in vivo segment of the study, 11 of 20 mice were injected with A. archangelica leaf extract, and 9 of them developed no or small tumors, whereas control mice developed tumors that were significantly larger. The antitumor properties of A. archangelica extract could not be attributed to the antiproliferative characteristics of the furanocoumarins in the extract (In Vivo 2005;19:191–4).
Significant antiproliferative activity has also been identified in the tincture of A. archangelica, using the human pancreas cancer cell line PANC-1 as a model. Investigators ascribed most of the antiproliferative activity to imperatorin and xanthotoxin, the two furanocoumarins most prevalent in the A. archangelica tincture (Z. Naturforsch. [C] 2004;59:523–7).
Dermatologic Potential
In addition to antitumorigenic activity, several Angelica species have exhibited properties pertinent to clinical dermatology. Hwaotang, a traditional Korean formulation that combines seven herbs, including A. gigas, exerts anti-inflammatory effects related to the inhibition of human neutrophil functions and of nitric oxide and prostaglandin E2 production (Immunopharmacol. Immunotoxicol. 2004;26:53–73).
In a study of the anti-inflammatory activity of a new formulation containing Synurus deltoides and A. gigas extracts, along with glucosamine sulfate, the medication (SAG) dose dependently inhibited ear edema in mice induced by arachidonic acid and TPA. Prostaglandin E2 production associated with mouse skin lesions was also significantly reduced by SAG, as well as by treatment with S. deltoides extract alone. The authors acknowledged that although SAG is not as potent as anti-inflammatory products in widespread use, this A. gigas-containing preparation has potential benefits as a neutraceutical therapy for inflammatory conditions (Arch. Pharm. Res. 2005;28:848–53).
A study of herbs used in traditional Chinese and Japanese medicine to treat acne revealed that the ethanol extract (0.01%) of Angelica dahurica substantially inhibited neutrophil chemotaxis, at a level comparable to that of erythromycin (0.01%). In the same study, Rhizoma coptidis displayed a stronger antilipogenic effect than did retinoic acid (0.01%), and Glycyrrhiza glabra (licorice) showed significant antibacterial activity against P. acnes. These results led the researchers to conclude that a formulation containing all three herbs would have potential in the prevention and treatment of acne (Skin Pharmacol. Appl. Skin Physiol. 2003;16:84–90). A. dahurica, which also contains lactones and psoralen, and has been used traditionally to treat psoriasis and for its reputed antihistamine effects.
In a study evaluating extracts from 15 plants used in traditional Chinese medicine to treat topical inflammations, investigators focused on the inhibitory effects on enzymes that are therapeutic targets in cutaneous conditions, specifically 5-lipoxygenase, cyclooxygenase, and elastase. Four plant species, including A. dahurica and A. pubescens, inhibited elastase in intact leukocytes and platelets (J. Pharm. Pharmacol. 2003;55:1275–82; Planta Med. 1998;64:525–9). In addition, A. pubescens has been found to confer analgesic and anti-inflammatory effects (Planta Med. 1995;61:2–8). One of the main active components isolated from A. pubescens, osthole, a coumarin compound, has also been shown to exert a nonspecific relaxant effect on the trachea of guinea pigs (Naunyn Schmiedebergs Arch. Pharmacol. 1994;349:202–8).
At the Store
Zestra Feminine Arousal Fluid (Zestra Laboratories Inc.) is a topical botanical formulation containing A. archangelica along with borage seed oil, evening primrose oil, ascorbyl palmitate, and alpha tocopherol. The product is intended to enhance female sexual pleasure and arousal.
Investigators conducted a randomized, double-blind, crossover study to assess the efficacy and safety of Zestra in 10 women with and 10 women without female sexual arousal disorder. Using questionnaires, participants reported on a range of sexual functions pertaining to home use of the formulation. The results indicated statistically significant overall improvements in sexual function in both test groups, compared with placebo (J. Sex Marital Ther. 2003;29 [Suppl 1]:33–44).
Conclusions
A wide range of Angelica species possess properties found to be of medical, including dermatologic, benefit. In addition to A. sinensis (discussed in this column in August), A. archangelica, A. dahurica, and A. gigas have been used successfully in traditional herbal medicines, and research is ongoing on these and other species, including A. keiskei, A. pubescens, and A. acutiloba.
While the overall body of research is slim on the efficacy of these herbs, the extant evidence supports further investigation and provides reasons for optimism. In the meantime, as is typical in the case of myriad botanic ingredients, there are several unproven formulations available to consumers that contain botanical cocktails including the biologically active Angelica species.
Besides Angelica sinensis, discussed last month, other species of Angelica have been studied for their medicinal potential, and, gradually, these species have been introduced into topical formulations.
Antitumor Activity
In a 2005 study, mice with highly metastatic drug-resistant tumors were used to test the effects of various herbal compounds on tumor growth and metastasis. Although the focus of the study was stilbene compounds, investigators found that two chalcone derivatives from Angelica keiskei roots inhibited tumor growth and metastasis. The chalcone derivatives worked by suppressing tumor-induced neovascularization and/or reducing the immune suppression brought on by tumors (In Vivo 2005;19:37–60).
Chalcone extracts of A. keiskei root, also known as ashitaba, which is consumed as a vegetable in Japan, also exhibited antitumorigenic activity in the two-phase mouse skin cancer model, in which carcinogenesis is induced by 7,12-dimethylbenz[a]anthracene (DMBA) and promoted by 12-O-tetradecanoylphorbol-13-acetate (TPA) (Planta Med. 1991;57:242–6).
In another study, xanthoangelol, a major chalcone constituent of A. keiskei, was found to dose-dependently decrease the survival rates of human neuroblastoma (IMR-32) and leukemia (Jurkat) cell lines. The findings indicated that the angelica component induced apoptosis by activating caspase-3 in neuroblastoma and leukemia cells without involving Bax/Bcl-2 proteins. The investigators concluded that xanthoangelol has potential as an agent against these cancers (Biol. Pharm. Bull. 2005;28:1404–7).
Other Angelica species besides keiskei and sinensis have shown antitumorigenic activity. Constituents of the Japanese drug shi-un-kou, which contains A. acutiloba, have been evaluated in assays. A. acutiloba alone and in combination with another constituent, Macrotomia euchroma, exhibited inhibitory effects, including reduced cytotoxicity, on Epstein-Barr virus activation induced by the tumor promoter TPA. The authors reported that a subsequent in vivo study in mice showed that shi-un-kou significantly inhibited skin tumor formation induced by TPA (Yakugaku Zasshi 1989;109:843–6).
In other research, investigators isolated the coumarin compound decursin from Korean angelica (A. gigantis, also known as A. gigas) root. They observed that decursin treatment for 24–96 hours strongly inhibited growth and dose-dependently induced apoptosis in human prostate carcinoma cells (Urol. Oncol. 2005;23:379–80).
In addition, another Angelica species, A. archangelica, exhibits antitumorigenic properties. Investigators evaluated the in vitro and in vivo effects of A. archangelica leaf extract on the growth of Crl mouse breast cancer cells. In vitro, the extract was found to be mildly antiproliferative. In the in vivo segment of the study, 11 of 20 mice were injected with A. archangelica leaf extract, and 9 of them developed no or small tumors, whereas control mice developed tumors that were significantly larger. The antitumor properties of A. archangelica extract could not be attributed to the antiproliferative characteristics of the furanocoumarins in the extract (In Vivo 2005;19:191–4).
Significant antiproliferative activity has also been identified in the tincture of A. archangelica, using the human pancreas cancer cell line PANC-1 as a model. Investigators ascribed most of the antiproliferative activity to imperatorin and xanthotoxin, the two furanocoumarins most prevalent in the A. archangelica tincture (Z. Naturforsch. [C] 2004;59:523–7).
Dermatologic Potential
In addition to antitumorigenic activity, several Angelica species have exhibited properties pertinent to clinical dermatology. Hwaotang, a traditional Korean formulation that combines seven herbs, including A. gigas, exerts anti-inflammatory effects related to the inhibition of human neutrophil functions and of nitric oxide and prostaglandin E2 production (Immunopharmacol. Immunotoxicol. 2004;26:53–73).
In a study of the anti-inflammatory activity of a new formulation containing Synurus deltoides and A. gigas extracts, along with glucosamine sulfate, the medication (SAG) dose dependently inhibited ear edema in mice induced by arachidonic acid and TPA. Prostaglandin E2 production associated with mouse skin lesions was also significantly reduced by SAG, as well as by treatment with S. deltoides extract alone. The authors acknowledged that although SAG is not as potent as anti-inflammatory products in widespread use, this A. gigas-containing preparation has potential benefits as a neutraceutical therapy for inflammatory conditions (Arch. Pharm. Res. 2005;28:848–53).
A study of herbs used in traditional Chinese and Japanese medicine to treat acne revealed that the ethanol extract (0.01%) of Angelica dahurica substantially inhibited neutrophil chemotaxis, at a level comparable to that of erythromycin (0.01%). In the same study, Rhizoma coptidis displayed a stronger antilipogenic effect than did retinoic acid (0.01%), and Glycyrrhiza glabra (licorice) showed significant antibacterial activity against P. acnes. These results led the researchers to conclude that a formulation containing all three herbs would have potential in the prevention and treatment of acne (Skin Pharmacol. Appl. Skin Physiol. 2003;16:84–90). A. dahurica, which also contains lactones and psoralen, and has been used traditionally to treat psoriasis and for its reputed antihistamine effects.
In a study evaluating extracts from 15 plants used in traditional Chinese medicine to treat topical inflammations, investigators focused on the inhibitory effects on enzymes that are therapeutic targets in cutaneous conditions, specifically 5-lipoxygenase, cyclooxygenase, and elastase. Four plant species, including A. dahurica and A. pubescens, inhibited elastase in intact leukocytes and platelets (J. Pharm. Pharmacol. 2003;55:1275–82; Planta Med. 1998;64:525–9). In addition, A. pubescens has been found to confer analgesic and anti-inflammatory effects (Planta Med. 1995;61:2–8). One of the main active components isolated from A. pubescens, osthole, a coumarin compound, has also been shown to exert a nonspecific relaxant effect on the trachea of guinea pigs (Naunyn Schmiedebergs Arch. Pharmacol. 1994;349:202–8).
At the Store
Zestra Feminine Arousal Fluid (Zestra Laboratories Inc.) is a topical botanical formulation containing A. archangelica along with borage seed oil, evening primrose oil, ascorbyl palmitate, and alpha tocopherol. The product is intended to enhance female sexual pleasure and arousal.
Investigators conducted a randomized, double-blind, crossover study to assess the efficacy and safety of Zestra in 10 women with and 10 women without female sexual arousal disorder. Using questionnaires, participants reported on a range of sexual functions pertaining to home use of the formulation. The results indicated statistically significant overall improvements in sexual function in both test groups, compared with placebo (J. Sex Marital Ther. 2003;29 [Suppl 1]:33–44).
Conclusions
A wide range of Angelica species possess properties found to be of medical, including dermatologic, benefit. In addition to A. sinensis (discussed in this column in August), A. archangelica, A. dahurica, and A. gigas have been used successfully in traditional herbal medicines, and research is ongoing on these and other species, including A. keiskei, A. pubescens, and A. acutiloba.
While the overall body of research is slim on the efficacy of these herbs, the extant evidence supports further investigation and provides reasons for optimism. In the meantime, as is typical in the case of myriad botanic ingredients, there are several unproven formulations available to consumers that contain botanical cocktails including the biologically active Angelica species.
Angelica: Part I
Angelica sinensis, better known as dong quai, is a fragrant perennial plant that has been used for medicinal purposes for more than a thousand years in China, Japan, and Korea. A. sinensis is best known as a traditional treatment for dysmenorrhea, amenorrhea, menopause, and related conditions in women.
The dried root of A. sinensis is included in several herbal formulations, typically for amenorrhea, endometriosis and premenstrual syndrome, and as a hormone replacement therapy alternative, even though Western medicine has not established whether such indications are appropriate or justified (Integrative Cancer Therapies 2003;2:120-38; Nurse Pract. 1997;22:55-6, 61-6).
Despite numerous anecdotal reports of its effectiveness in exerting estrogenic effects, a study of 71 postmenopausal women showed that A. sinensis alone failed to produce estrogenic effects on endometrial thickness or vaginal maturation. In addition, the herb eased menopause symptoms no better than placebo (Fertil. Steril. 1997;68:981-6).
Although the reported effects of this reputed “women's herb” remain dubious in the West, evidence is increasing that A. sinensis possesses anticarcinogenic properties, which are often associated with antioxidant potential and implications for dermatologic use.
In this vein, the potent antioxidant ferulic acid, which was featured in this column in October 2005, has been identified as a major active component of A. sinensis, along with ligustilide (J. Pharm. Biomed. Anal. 2005;38:664-9).
Antitumor Action
Investigators assessing the antitumor effects, in vitro and in vivo, of a chloroform extract of A. sinensis on glioblastoma multiforme brain tumors reported that the herb strongly inhibits the growth of malignant brain tumor cells, via cell cycle arrest and apoptosis induction, without damaging fibroblasts.
In vitro, angelica spurred p53-dependent and -independent pathways, resulting in apoptosis. In human DBTRG-05MG and rat RG2 glioblastoma multiforme tumor cells, angelica suppressed malignant growth and reduced tumor volume. Researchers concluded that A. sinensis merits more research and consideration as a potential brain tumor therapeutic agent (Clin. Cancer Res. 2005;11:3475-84).
In a study that assessed the antioxidant activities of three herbs used frequently in traditional Chinese medicine—A. sinensis, Lycium barbarum, and Poria cocos—aqueous extracts of these herbs concentration-dependently displayed antioxidant activities. L. barbarum extract was the strongest, but all the extracts inhibited ferric chloride-ascorbic acid-induced lipid peroxidation in rat liver homogenate in vitro, and demonstrated significant superoxide anion-scavenging activity as well as antisuperoxide formation activity (Phytother. Res. 2004;18:1008-12).
Another study revealed that the total polysaccharide from A. sinensis confers antitumor effects on in vivo murine models and, in vitro, inhibits invasion and metastasis of hepatocellular cancer cells (World J. Gastroenterol. 2003;9:1963-7).
In a study of the effects of 14 commonly used herbs on cellular proliferation and apoptosis of a hepatic stellate cell line in rats, A. sinensis was among five herbs that exhibited both antiproliferative and proapoptotic properties in association with upregulation of Fas and Bax and downregulation of Bcl-xL. Investigators suggested that further research is warranted into the antifibrotic potential of these herbs to promote apoptosis in hepatic stellate cells, which are integral in hepatic fibrosis and are known to possess antifibrotic activity (J. Ethnopharmacol. 2005;100:180-6).
Action in the Skin
Perhaps the evidence providing the most direct link to dermatologic application comes from a study of the effects of A. sinensis on melanocytes and tyrosinase activity. The potent herb was noted for significantly promoting melanocytic proliferation, which substantially increased cell counts, and fostering melanin synthesis and melanocytic tyrosinase activity. Such actions, the investigators concluded, suggest a mechanism that may justify the use of this fragrant botanical in the treatment of skin dyschromias (Di Yi Jun Yi Da Xue Xue Bao 2003;23:239-41).
In addition, A. sinensis is an ingredient in Si-Wu-Tang, a traditional Chinese formula used to treat pruritus, chronic skin inflammation, and other conditions (Biol. Pharm. Bull. 2002;25:1175-8).
Gastrointestinal Protection
Polysaccharides isolated from the root of A. sinensis have been found to impart an ulcer-protective effect.
Specifically, angelica extract dose-dependently inhibited various neutrophil-dependent gastrointestinal lesions induced in rats by orally administered ethanol or indomethacin. The investigators concluded that angelica exhibits anti-inflammatory action, and might be effective in preventing neutrophil-dependent gastrointestinal damage (Planta Med. 2000;66:348-51).
Some of the same researchers followed up by demonstrating that A. sinensis extract has a direct wound-healing effect on gastric epithelial cells. The herb significantly promoted epithelial cell migration over an artificial wound, and dose-dependently stimulated DNA synthesis as well as concurrent epithelial growth factor mRNA expression (Life Sci. 2001;68:961-8).
Subsequent research confirmed that A. sinensis crude extract does dose-dependently confer a direct healing effect on gastric mucosal lesions in rats, and it also promotes wound repair in culture (Biochem. Pharmacol. 2001;61:1439-48).
Other Actions
An evaluation of the therapeutic activity of A. sinensis on focal ischemic injury in rats showed reduced volume of cerebral infarction, reduced Bax protein expression, and significant decreases in the number of neuronal apoptosis cells (Clin. Hemorheol. Microcirc. 2005;32:209-15). Improvement in microcirculation, with obvious implications for various organs, was achieved by the intravenous injection of A. sinensis in a study examining the mechanism of microcirculation disorder in the tongue in the common oral disease glossodynia (Hua Xi Kou Qiang Yi Xue Za Zhi 2000;18:101-2, 108).
Aqueous extract of A. sinensis has been shown in a rabbit model to impart myocardial protective effects caused by ischemia reperfusion (Zhongguo Zhong Xi Yi Jie He Za Zhi 1995;15:486-8).
A study of the effects of two herbs used in traditional Chinese medicine to treat bleomycin-induced pulmonary fibrosis in rats revealed that ligustrazini and, to a lesser extent, A. sinensis, lessened the severity of alveolitis symptomatic of pulmonary fibrosis (Zhonghua Jie He He Hu Xi Za Zhi 1996;19:26-8).
Similarly, a traditional Chinese medicinal decoction containing A. sinensis and Astragalus membranaceus, which is used for stimulating production of red blood cells and bolstering cardiovascular function, was shown in a rat model to confer myocardial protection against ischemia-reperfusion injury (Phytother. Res. 2000;14:195-9).
Injection of Qi-Xue, another Chinese herb combination containing A. sinensis, Panax ginseng, and Astragalus monogholicus, is thought to prevent severe hypoxic pulmonary hypertension by enhancing heart function (Zhongguo Yi Xue Ke Xue Yuan Xue Bao 1990;12:51-5).
In high doses, A. sinensis may increase susceptibility to photosensitivity reactions, so sun exposure should be curtailed. It also is contraindicated for patients taking warfarin (Lancet 2000; 355:134-8; J. Am. Med. Womens Assoc. 1999;54:191-2, 195).
Conclusions
A. sinensis is one of the oldest and most popular herbs used in traditional Chinese medicine. While there is an expanding body of research on the broad medical applications of this botanical product, and it is being used in multibotanical formulations, there is minimal evidence as yet to warrant its use for dermatologic purposes.
Recent studies, however, do seem to indicate that A. sinensis has antioxidant and antitumorigenic activity and that it warrants further investigation, including for its potential benefit to the skin. Research associating angelica with melanocytic, anti-inflammatory, and antipruritic properties also deserves attention and further study.
Although little dermatologic research has been done, the Angelica sinensis plant, also known as dong quai, appears to have antioxidant and antitumorigenic activity.
Photo ©adisa/iStockphoto, Inc.
Angelica sinensis, better known as dong quai, is a fragrant perennial plant that has been used for medicinal purposes for more than a thousand years in China, Japan, and Korea. A. sinensis is best known as a traditional treatment for dysmenorrhea, amenorrhea, menopause, and related conditions in women.
The dried root of A. sinensis is included in several herbal formulations, typically for amenorrhea, endometriosis and premenstrual syndrome, and as a hormone replacement therapy alternative, even though Western medicine has not established whether such indications are appropriate or justified (Integrative Cancer Therapies 2003;2:120-38; Nurse Pract. 1997;22:55-6, 61-6).
Despite numerous anecdotal reports of its effectiveness in exerting estrogenic effects, a study of 71 postmenopausal women showed that A. sinensis alone failed to produce estrogenic effects on endometrial thickness or vaginal maturation. In addition, the herb eased menopause symptoms no better than placebo (Fertil. Steril. 1997;68:981-6).
Although the reported effects of this reputed “women's herb” remain dubious in the West, evidence is increasing that A. sinensis possesses anticarcinogenic properties, which are often associated with antioxidant potential and implications for dermatologic use.
In this vein, the potent antioxidant ferulic acid, which was featured in this column in October 2005, has been identified as a major active component of A. sinensis, along with ligustilide (J. Pharm. Biomed. Anal. 2005;38:664-9).
Antitumor Action
Investigators assessing the antitumor effects, in vitro and in vivo, of a chloroform extract of A. sinensis on glioblastoma multiforme brain tumors reported that the herb strongly inhibits the growth of malignant brain tumor cells, via cell cycle arrest and apoptosis induction, without damaging fibroblasts.
In vitro, angelica spurred p53-dependent and -independent pathways, resulting in apoptosis. In human DBTRG-05MG and rat RG2 glioblastoma multiforme tumor cells, angelica suppressed malignant growth and reduced tumor volume. Researchers concluded that A. sinensis merits more research and consideration as a potential brain tumor therapeutic agent (Clin. Cancer Res. 2005;11:3475-84).
In a study that assessed the antioxidant activities of three herbs used frequently in traditional Chinese medicine—A. sinensis, Lycium barbarum, and Poria cocos—aqueous extracts of these herbs concentration-dependently displayed antioxidant activities. L. barbarum extract was the strongest, but all the extracts inhibited ferric chloride-ascorbic acid-induced lipid peroxidation in rat liver homogenate in vitro, and demonstrated significant superoxide anion-scavenging activity as well as antisuperoxide formation activity (Phytother. Res. 2004;18:1008-12).
Another study revealed that the total polysaccharide from A. sinensis confers antitumor effects on in vivo murine models and, in vitro, inhibits invasion and metastasis of hepatocellular cancer cells (World J. Gastroenterol. 2003;9:1963-7).
In a study of the effects of 14 commonly used herbs on cellular proliferation and apoptosis of a hepatic stellate cell line in rats, A. sinensis was among five herbs that exhibited both antiproliferative and proapoptotic properties in association with upregulation of Fas and Bax and downregulation of Bcl-xL. Investigators suggested that further research is warranted into the antifibrotic potential of these herbs to promote apoptosis in hepatic stellate cells, which are integral in hepatic fibrosis and are known to possess antifibrotic activity (J. Ethnopharmacol. 2005;100:180-6).
Action in the Skin
Perhaps the evidence providing the most direct link to dermatologic application comes from a study of the effects of A. sinensis on melanocytes and tyrosinase activity. The potent herb was noted for significantly promoting melanocytic proliferation, which substantially increased cell counts, and fostering melanin synthesis and melanocytic tyrosinase activity. Such actions, the investigators concluded, suggest a mechanism that may justify the use of this fragrant botanical in the treatment of skin dyschromias (Di Yi Jun Yi Da Xue Xue Bao 2003;23:239-41).
In addition, A. sinensis is an ingredient in Si-Wu-Tang, a traditional Chinese formula used to treat pruritus, chronic skin inflammation, and other conditions (Biol. Pharm. Bull. 2002;25:1175-8).
Gastrointestinal Protection
Polysaccharides isolated from the root of A. sinensis have been found to impart an ulcer-protective effect.
Specifically, angelica extract dose-dependently inhibited various neutrophil-dependent gastrointestinal lesions induced in rats by orally administered ethanol or indomethacin. The investigators concluded that angelica exhibits anti-inflammatory action, and might be effective in preventing neutrophil-dependent gastrointestinal damage (Planta Med. 2000;66:348-51).
Some of the same researchers followed up by demonstrating that A. sinensis extract has a direct wound-healing effect on gastric epithelial cells. The herb significantly promoted epithelial cell migration over an artificial wound, and dose-dependently stimulated DNA synthesis as well as concurrent epithelial growth factor mRNA expression (Life Sci. 2001;68:961-8).
Subsequent research confirmed that A. sinensis crude extract does dose-dependently confer a direct healing effect on gastric mucosal lesions in rats, and it also promotes wound repair in culture (Biochem. Pharmacol. 2001;61:1439-48).
Other Actions
An evaluation of the therapeutic activity of A. sinensis on focal ischemic injury in rats showed reduced volume of cerebral infarction, reduced Bax protein expression, and significant decreases in the number of neuronal apoptosis cells (Clin. Hemorheol. Microcirc. 2005;32:209-15). Improvement in microcirculation, with obvious implications for various organs, was achieved by the intravenous injection of A. sinensis in a study examining the mechanism of microcirculation disorder in the tongue in the common oral disease glossodynia (Hua Xi Kou Qiang Yi Xue Za Zhi 2000;18:101-2, 108).
Aqueous extract of A. sinensis has been shown in a rabbit model to impart myocardial protective effects caused by ischemia reperfusion (Zhongguo Zhong Xi Yi Jie He Za Zhi 1995;15:486-8).
A study of the effects of two herbs used in traditional Chinese medicine to treat bleomycin-induced pulmonary fibrosis in rats revealed that ligustrazini and, to a lesser extent, A. sinensis, lessened the severity of alveolitis symptomatic of pulmonary fibrosis (Zhonghua Jie He He Hu Xi Za Zhi 1996;19:26-8).
Similarly, a traditional Chinese medicinal decoction containing A. sinensis and Astragalus membranaceus, which is used for stimulating production of red blood cells and bolstering cardiovascular function, was shown in a rat model to confer myocardial protection against ischemia-reperfusion injury (Phytother. Res. 2000;14:195-9).
Injection of Qi-Xue, another Chinese herb combination containing A. sinensis, Panax ginseng, and Astragalus monogholicus, is thought to prevent severe hypoxic pulmonary hypertension by enhancing heart function (Zhongguo Yi Xue Ke Xue Yuan Xue Bao 1990;12:51-5).
In high doses, A. sinensis may increase susceptibility to photosensitivity reactions, so sun exposure should be curtailed. It also is contraindicated for patients taking warfarin (Lancet 2000; 355:134-8; J. Am. Med. Womens Assoc. 1999;54:191-2, 195).
Conclusions
A. sinensis is one of the oldest and most popular herbs used in traditional Chinese medicine. While there is an expanding body of research on the broad medical applications of this botanical product, and it is being used in multibotanical formulations, there is minimal evidence as yet to warrant its use for dermatologic purposes.
Recent studies, however, do seem to indicate that A. sinensis has antioxidant and antitumorigenic activity and that it warrants further investigation, including for its potential benefit to the skin. Research associating angelica with melanocytic, anti-inflammatory, and antipruritic properties also deserves attention and further study.
Although little dermatologic research has been done, the Angelica sinensis plant, also known as dong quai, appears to have antioxidant and antitumorigenic activity.
Photo ©adisa/iStockphoto, Inc.
Angelica sinensis, better known as dong quai, is a fragrant perennial plant that has been used for medicinal purposes for more than a thousand years in China, Japan, and Korea. A. sinensis is best known as a traditional treatment for dysmenorrhea, amenorrhea, menopause, and related conditions in women.
The dried root of A. sinensis is included in several herbal formulations, typically for amenorrhea, endometriosis and premenstrual syndrome, and as a hormone replacement therapy alternative, even though Western medicine has not established whether such indications are appropriate or justified (Integrative Cancer Therapies 2003;2:120-38; Nurse Pract. 1997;22:55-6, 61-6).
Despite numerous anecdotal reports of its effectiveness in exerting estrogenic effects, a study of 71 postmenopausal women showed that A. sinensis alone failed to produce estrogenic effects on endometrial thickness or vaginal maturation. In addition, the herb eased menopause symptoms no better than placebo (Fertil. Steril. 1997;68:981-6).
Although the reported effects of this reputed “women's herb” remain dubious in the West, evidence is increasing that A. sinensis possesses anticarcinogenic properties, which are often associated with antioxidant potential and implications for dermatologic use.
In this vein, the potent antioxidant ferulic acid, which was featured in this column in October 2005, has been identified as a major active component of A. sinensis, along with ligustilide (J. Pharm. Biomed. Anal. 2005;38:664-9).
Antitumor Action
Investigators assessing the antitumor effects, in vitro and in vivo, of a chloroform extract of A. sinensis on glioblastoma multiforme brain tumors reported that the herb strongly inhibits the growth of malignant brain tumor cells, via cell cycle arrest and apoptosis induction, without damaging fibroblasts.
In vitro, angelica spurred p53-dependent and -independent pathways, resulting in apoptosis. In human DBTRG-05MG and rat RG2 glioblastoma multiforme tumor cells, angelica suppressed malignant growth and reduced tumor volume. Researchers concluded that A. sinensis merits more research and consideration as a potential brain tumor therapeutic agent (Clin. Cancer Res. 2005;11:3475-84).
In a study that assessed the antioxidant activities of three herbs used frequently in traditional Chinese medicine—A. sinensis, Lycium barbarum, and Poria cocos—aqueous extracts of these herbs concentration-dependently displayed antioxidant activities. L. barbarum extract was the strongest, but all the extracts inhibited ferric chloride-ascorbic acid-induced lipid peroxidation in rat liver homogenate in vitro, and demonstrated significant superoxide anion-scavenging activity as well as antisuperoxide formation activity (Phytother. Res. 2004;18:1008-12).
Another study revealed that the total polysaccharide from A. sinensis confers antitumor effects on in vivo murine models and, in vitro, inhibits invasion and metastasis of hepatocellular cancer cells (World J. Gastroenterol. 2003;9:1963-7).
In a study of the effects of 14 commonly used herbs on cellular proliferation and apoptosis of a hepatic stellate cell line in rats, A. sinensis was among five herbs that exhibited both antiproliferative and proapoptotic properties in association with upregulation of Fas and Bax and downregulation of Bcl-xL. Investigators suggested that further research is warranted into the antifibrotic potential of these herbs to promote apoptosis in hepatic stellate cells, which are integral in hepatic fibrosis and are known to possess antifibrotic activity (J. Ethnopharmacol. 2005;100:180-6).
Action in the Skin
Perhaps the evidence providing the most direct link to dermatologic application comes from a study of the effects of A. sinensis on melanocytes and tyrosinase activity. The potent herb was noted for significantly promoting melanocytic proliferation, which substantially increased cell counts, and fostering melanin synthesis and melanocytic tyrosinase activity. Such actions, the investigators concluded, suggest a mechanism that may justify the use of this fragrant botanical in the treatment of skin dyschromias (Di Yi Jun Yi Da Xue Xue Bao 2003;23:239-41).
In addition, A. sinensis is an ingredient in Si-Wu-Tang, a traditional Chinese formula used to treat pruritus, chronic skin inflammation, and other conditions (Biol. Pharm. Bull. 2002;25:1175-8).
Gastrointestinal Protection
Polysaccharides isolated from the root of A. sinensis have been found to impart an ulcer-protective effect.
Specifically, angelica extract dose-dependently inhibited various neutrophil-dependent gastrointestinal lesions induced in rats by orally administered ethanol or indomethacin. The investigators concluded that angelica exhibits anti-inflammatory action, and might be effective in preventing neutrophil-dependent gastrointestinal damage (Planta Med. 2000;66:348-51).
Some of the same researchers followed up by demonstrating that A. sinensis extract has a direct wound-healing effect on gastric epithelial cells. The herb significantly promoted epithelial cell migration over an artificial wound, and dose-dependently stimulated DNA synthesis as well as concurrent epithelial growth factor mRNA expression (Life Sci. 2001;68:961-8).
Subsequent research confirmed that A. sinensis crude extract does dose-dependently confer a direct healing effect on gastric mucosal lesions in rats, and it also promotes wound repair in culture (Biochem. Pharmacol. 2001;61:1439-48).
Other Actions
An evaluation of the therapeutic activity of A. sinensis on focal ischemic injury in rats showed reduced volume of cerebral infarction, reduced Bax protein expression, and significant decreases in the number of neuronal apoptosis cells (Clin. Hemorheol. Microcirc. 2005;32:209-15). Improvement in microcirculation, with obvious implications for various organs, was achieved by the intravenous injection of A. sinensis in a study examining the mechanism of microcirculation disorder in the tongue in the common oral disease glossodynia (Hua Xi Kou Qiang Yi Xue Za Zhi 2000;18:101-2, 108).
Aqueous extract of A. sinensis has been shown in a rabbit model to impart myocardial protective effects caused by ischemia reperfusion (Zhongguo Zhong Xi Yi Jie He Za Zhi 1995;15:486-8).
A study of the effects of two herbs used in traditional Chinese medicine to treat bleomycin-induced pulmonary fibrosis in rats revealed that ligustrazini and, to a lesser extent, A. sinensis, lessened the severity of alveolitis symptomatic of pulmonary fibrosis (Zhonghua Jie He He Hu Xi Za Zhi 1996;19:26-8).
Similarly, a traditional Chinese medicinal decoction containing A. sinensis and Astragalus membranaceus, which is used for stimulating production of red blood cells and bolstering cardiovascular function, was shown in a rat model to confer myocardial protection against ischemia-reperfusion injury (Phytother. Res. 2000;14:195-9).
Injection of Qi-Xue, another Chinese herb combination containing A. sinensis, Panax ginseng, and Astragalus monogholicus, is thought to prevent severe hypoxic pulmonary hypertension by enhancing heart function (Zhongguo Yi Xue Ke Xue Yuan Xue Bao 1990;12:51-5).
In high doses, A. sinensis may increase susceptibility to photosensitivity reactions, so sun exposure should be curtailed. It also is contraindicated for patients taking warfarin (Lancet 2000; 355:134-8; J. Am. Med. Womens Assoc. 1999;54:191-2, 195).
Conclusions
A. sinensis is one of the oldest and most popular herbs used in traditional Chinese medicine. While there is an expanding body of research on the broad medical applications of this botanical product, and it is being used in multibotanical formulations, there is minimal evidence as yet to warrant its use for dermatologic purposes.
Recent studies, however, do seem to indicate that A. sinensis has antioxidant and antitumorigenic activity and that it warrants further investigation, including for its potential benefit to the skin. Research associating angelica with melanocytic, anti-inflammatory, and antipruritic properties also deserves attention and further study.
Although little dermatologic research has been done, the Angelica sinensis plant, also known as dong quai, appears to have antioxidant and antitumorigenic activity.
Photo ©adisa/iStockphoto, Inc.
Triterpenoids
Triterpenoids, to which squalene is the immediate biologic precursor, include steroids and, thus, sterols, and represent the largest group of terpenoids, the most abundant group of botanical constituents and the most common ingredient class found in volatile oils. Consequently, triterpenoids appear in numerous botanical products with traditional and modern applications to dermatology, such as Centella asiatica (gotu kola) and propolis.
Indeed, the naturally occurring triterpenoids, oleanolic acid and ursolic acid, are known to confer anticarcinogenic and anti-inflammatory effects in certain cells (Exp. Dermatol. 2006;15:66–73). Ursolic acid and the natural triterpenoid erythrodiol have also been found to be effective in a multiple-dose 12-O-tetradecanoylphorbol-13-acetate (TPA) model of chronic dermal inflammation (Eur. J. Pharmacol. 1997;334:103–5).
Although triterpenoids are not as prevalent in as many of the highly touted herbal sources as polyphenols, this group of compounds is gaining increased attention for its anti-inflammatory and anti-tumor-promoting activity. In one trial, investigators studying the triterpenoids oleanolic acid and ursolic acid found that the former induced the differentiation of keratinocytes through peroxisome proliferator-activated receptor (PPAR)-α activation. In addition, topical application of oleanolic acid improved the recovery of epidermal permeability barrier function and increased ceramides in epidermis (Exp. Dermatol. 2006;15:66–73).
The preponderance of data on triterpenoids, though, points to the anti-tumor-promoting capacity of this copious botanical class of compounds.
Anti-Tumor-Promoting Actions
In a study designed to identify potential anti-tumor promoters, investigators screened 21 cucurbitane triterpenoids using an in vitro assay system, and found that several of the compounds significantly inhibited Epstein-Barr virus (EBV) activation induced by the tumor promoter TPA.
These compounds were scandenoside R6, 23,24-dihydrocucurbitacin F, 25-acetyl-23,24-dihydrocucurbitacin F, 2-O-beta-D-glucopyranosyl-23,24-dihydrocucurbitacin F, and cucurbitacin F. Two triterpenoids, 23,24-dihydrocucurbitacin F and 2-O-beta-D-glucopyranosyl-23,24-dihydrocucurbitacin F, also displayed significant activity against skin tumor promotion in an in vivo two-stage murine carcinogenesis model (Biol. Pharm. Bull. 1994;17:668–71).
A later in vitro study conducted by the same lab to identify anti-tumor promoters considered 23 triterpenoid hydrocarbons isolated from ferns. Significant inhibitory activity against EBV induced by TPA was exhibited by hop-17(21)-ene, neohop-13(18)-ene, neohop-12-ene, taraxerane, multiflor-9(11)-ene, multiflor-8-ene, glutin-5(10)-ene, and taraxastane. In a two-stage in vivo murine carcinogenesis model using 7,12-dimethylbenz[a]anthracene (DMBA) for initiation and TPA for promotion, hop-17(21)-ene and neohop-13(18)-ene displayed significant anti-tumor promoting effects on mouse skin (Biol. Pharm. Bull. 1996;19:962–5).
Three years later, some of the same investigators, studying triterpenoids derived from Taraxacum japonicum (Compositae) roots, found that taraxasterol and taraxerol significantly inhibited the effects of TPA-induced Epstein-Barr virus early antigen (EBV-EA) induction, which is a preliminary in vitro screening approach to identifying anti-tumor-promoting agents. These compounds also exhibited potent anti-tumor-promoting activity in the two-stage murine skin carcinogenesis model initiated by DMBA and promoted by TPA (Biol. Pharm. Bull. 1999;22:606–10).
In a study from Osaka (Japan) University of Pharmaceutical Sciences, seven serratane-type triterpenoids isolated from different Picea species all exhibited potent inhibitory effects on EBV-EA activation induced by TPA, and did so more strongly than oleanolic acid. In addition, 13alpha,14alpha-epoxy-3beta-methoxyserratan-21beta-ol displayed significant anti-tumor-promoting activity in the in vivo two-stage murine carcinogenesis model (Cancer Lett. 2001;172:119–26).
The same lab subsequently studied 11 serratane-type triterpenoids isolated from various Picea species and three synthetic analogues for their potential inhibitory effects on EBV-EA activation induced by TPA. That study yielded more corroborative findings, as several of the compounds showed potent inhibitory activity, again more strongly than the oleanolic control, including 21-episerratenediol, serratenediol, diepiserratenediol, 3-beta-hydroxyserrat-14-en-21-one, and 3-alpha-methoxy-21-beta-hydroxyserrat-14-en-16-one. Furthermore, no cytotoxicity was associated with these compounds.
Of these triterpenoids, 21-episerratenediol was found to demonstrate significant inhibitory effects on skin tumor promotion in the in vivo two-stage mouse skin carcinogenesis model using DMBA for initiation and TPA for promotion. The investigators suggested that the triterpenoid 21-episerratenediol has potential as an effective cancer chemopreventive agent (Cancer Lett. 2003;196:121–6).
In a separate experiment conducted by this lab, two new serratane-type triterpenoids, 3beta-methoxyserrat-13-en-21-beta-ol and 13-beta,14beta-epoxy-3beta-methoxyserratan-21beta-ol, also isolated from Picea plants, exhibited strong anti-tumor-promoting effects on mouse skin carcinogenesis (Planta Med. 2003;69:1041–7).
This lab also showed that, in a test of the lupane-type triterpenoids isolated from the stem bark of Glochidion zeylanicum as well as synthetic analogues, glochidiol and lup-20(29)-ene-1beta,3beta-diol were the strongest inhibitors of EBV-EA activation induced by TPA. Glochidiol also exhibited the greatest inhibitory effect on skin tumor promotion (Planta Med. 2004;70:1234–6).
Other Anticarcinogenic Actions
In 2005, investigators at the University of North Carolina, Chapel Hill, published a report on cimigenol, an acid- and base-stable triterpenoid found in species such as Cimicifuga racemosa, C. dahurica, and C. japonica. These researchers had previously shown that cimigenol and some of its derivatives had strong inhibitory effects on mouse skin tumor promotion induced by TPA in a two-stage carcinogenesis test. Continuing that previous work, the investigators repeated screens of cimigenol and also tested 15 related compounds as potential anti-tumor promoters by using the in vitro, short-term TPA-induced EBV-EA activation assay (Bioorg. Med. Chem. 2005;13:1403–8).
Of these compounds, the researchers found that cimigenol-3,15-dione showed the greatest potency and, in a subsequent two-stage DMBA/TPA carcinogenesis assay, reduced, at 20 weeks, the number of papillomas per mouse to 48% of controls. Both cimigenol and cimigenol-3,15-dione were also nearly as potent as epigallocatechin gallate, a primary constituent of green tea, in terms of anti-tumor initiation activity, as demonstrated in a two-stage carcinogenesis assay of mouse skin tumors induced by peroxynitrite (initiator) and TPA (promoter).
The investigators concluded that these two triterpenoids amply demonstrate anti-tumor promotion as well as anti-tumor initiation and warrant consideration as significant cancer chemopreventive agents (Bioorg. Med. Chem. 2005;13:1403–8).
Protection Against UV
Four triterpenoids isolated from the stems of Styrax japonica were recently found to significantly inhibit matrix metalloproteinase-1 (MMP-1) in primary human skin fibroblasts induced by UV radiation. This finding is significant given the association between the upregulation of MMPs and chronic skin damage (Biol. Pharm. Bull. 2005;28:2003–6).
Previously, some of the same investigators studied the effects of 3,23-dihydroxy-20(29)-lupen-27-oic acid, a triterpenoid derived from Tiarella polyphylla, on the regulation of MMP-1 and type 1 procollagen in UV irradiation of cultured old-age human dermal fibroblasts. The triterpenoid dose-dependently induced regulation of type 1 procollagen and diminished regulation of MMP-1 at the protein level (Arch. Pharm. Res. 2004;27:1060–4).
Other Pharmacologic Actions
Triterpenoids also have been found in Boswellia serrata, an herb used in traditional medicine to treat inflammatory and arthritic conditions (and discussed in this column in November 2006, p. 17).
In a study published in 2000, the primary components and derivatives of Boswellia markedly inhibited TPA-induced increases in skin inflammation, epidermal proliferation, the number of epidermal cell layers, and tumor promotion in DMBA-initiated mice. DNA synthesis in human leukemia HL-60 cells was also shown to be inhibited by the addition of various forms of boswellic acid. The investigators suggest that such findings demonstrate the anticarcinogenic and antitumor properties of the major constituents, including triterpenoids, of this herb (Biofactors 2000;13:225–30).
The anti-inflammatory activity of several triterpenoids suggests the potential for numerous additional medical applications. A study evaluating the mechanism of anti-inflammatory activity displayed by triterpenoids on edema induced in mouse ears and paws, as well as rat skin, revealed that the inhibition of protein kinase C may play a crucial role in facilitating the anti-inflammatory activity of this class of compounds (Eur. J. Pharmacol. 2000;410:69–81).
In another study, several triterpene constituents of Vochysia pacifica Cuatrec, a South American tree used by traditional communities to treat inflammation, skin sores, asthma, and pulmonary congestion, were found to exert mild inhibitory activity on the intracellular target for new anti-inflammatory medications, namely the cAMP phosphodiesterase 4 isozyme (PDE4) (Phytother. Res. 2005;19:75–7).
Some triterpenoids have been documented as irritating (J. Asian Nat. Prod. Res. 2003;5:35–41) and others as toxic, which is not unexpected as these compounds comprise the primary constituent class in the volatile oils of plants. Given the breadth of this biochemical class, it is expected that some members would be toxic and others safe and beneficial to human health, such as the triterpenoid saponin glycyrrhizin, derived from licorice root (and featured in this column in March 2007, p. 24, and April 2007, p. 30). Triterpenoid saponins, or sapogenins, are used in some emulsifiers, including some Estée Lauder products, for their capacity to confer antifungal, anti-inflammatory, antimicrobial, and adaptogenic activity.
Conclusion
As we continue to explore botanical sources for medical and cosmetic purposes, we will learn more about the numerous triterpenoids found in plants. This class of biochemical compounds typically receives less attention than polyphenols in discussions of the most potent herbal ingredients used in dermatology, but the considerable potential of triterpenoids to be used in a broad range of cutaneous applications is gradually becoming appreciated.
Triterpenoids, to which squalene is the immediate biologic precursor, include steroids and, thus, sterols, and represent the largest group of terpenoids, the most abundant group of botanical constituents and the most common ingredient class found in volatile oils. Consequently, triterpenoids appear in numerous botanical products with traditional and modern applications to dermatology, such as Centella asiatica (gotu kola) and propolis.
Indeed, the naturally occurring triterpenoids, oleanolic acid and ursolic acid, are known to confer anticarcinogenic and anti-inflammatory effects in certain cells (Exp. Dermatol. 2006;15:66–73). Ursolic acid and the natural triterpenoid erythrodiol have also been found to be effective in a multiple-dose 12-O-tetradecanoylphorbol-13-acetate (TPA) model of chronic dermal inflammation (Eur. J. Pharmacol. 1997;334:103–5).
Although triterpenoids are not as prevalent in as many of the highly touted herbal sources as polyphenols, this group of compounds is gaining increased attention for its anti-inflammatory and anti-tumor-promoting activity. In one trial, investigators studying the triterpenoids oleanolic acid and ursolic acid found that the former induced the differentiation of keratinocytes through peroxisome proliferator-activated receptor (PPAR)-α activation. In addition, topical application of oleanolic acid improved the recovery of epidermal permeability barrier function and increased ceramides in epidermis (Exp. Dermatol. 2006;15:66–73).
The preponderance of data on triterpenoids, though, points to the anti-tumor-promoting capacity of this copious botanical class of compounds.
Anti-Tumor-Promoting Actions
In a study designed to identify potential anti-tumor promoters, investigators screened 21 cucurbitane triterpenoids using an in vitro assay system, and found that several of the compounds significantly inhibited Epstein-Barr virus (EBV) activation induced by the tumor promoter TPA.
These compounds were scandenoside R6, 23,24-dihydrocucurbitacin F, 25-acetyl-23,24-dihydrocucurbitacin F, 2-O-beta-D-glucopyranosyl-23,24-dihydrocucurbitacin F, and cucurbitacin F. Two triterpenoids, 23,24-dihydrocucurbitacin F and 2-O-beta-D-glucopyranosyl-23,24-dihydrocucurbitacin F, also displayed significant activity against skin tumor promotion in an in vivo two-stage murine carcinogenesis model (Biol. Pharm. Bull. 1994;17:668–71).
A later in vitro study conducted by the same lab to identify anti-tumor promoters considered 23 triterpenoid hydrocarbons isolated from ferns. Significant inhibitory activity against EBV induced by TPA was exhibited by hop-17(21)-ene, neohop-13(18)-ene, neohop-12-ene, taraxerane, multiflor-9(11)-ene, multiflor-8-ene, glutin-5(10)-ene, and taraxastane. In a two-stage in vivo murine carcinogenesis model using 7,12-dimethylbenz[a]anthracene (DMBA) for initiation and TPA for promotion, hop-17(21)-ene and neohop-13(18)-ene displayed significant anti-tumor promoting effects on mouse skin (Biol. Pharm. Bull. 1996;19:962–5).
Three years later, some of the same investigators, studying triterpenoids derived from Taraxacum japonicum (Compositae) roots, found that taraxasterol and taraxerol significantly inhibited the effects of TPA-induced Epstein-Barr virus early antigen (EBV-EA) induction, which is a preliminary in vitro screening approach to identifying anti-tumor-promoting agents. These compounds also exhibited potent anti-tumor-promoting activity in the two-stage murine skin carcinogenesis model initiated by DMBA and promoted by TPA (Biol. Pharm. Bull. 1999;22:606–10).
In a study from Osaka (Japan) University of Pharmaceutical Sciences, seven serratane-type triterpenoids isolated from different Picea species all exhibited potent inhibitory effects on EBV-EA activation induced by TPA, and did so more strongly than oleanolic acid. In addition, 13alpha,14alpha-epoxy-3beta-methoxyserratan-21beta-ol displayed significant anti-tumor-promoting activity in the in vivo two-stage murine carcinogenesis model (Cancer Lett. 2001;172:119–26).
The same lab subsequently studied 11 serratane-type triterpenoids isolated from various Picea species and three synthetic analogues for their potential inhibitory effects on EBV-EA activation induced by TPA. That study yielded more corroborative findings, as several of the compounds showed potent inhibitory activity, again more strongly than the oleanolic control, including 21-episerratenediol, serratenediol, diepiserratenediol, 3-beta-hydroxyserrat-14-en-21-one, and 3-alpha-methoxy-21-beta-hydroxyserrat-14-en-16-one. Furthermore, no cytotoxicity was associated with these compounds.
Of these triterpenoids, 21-episerratenediol was found to demonstrate significant inhibitory effects on skin tumor promotion in the in vivo two-stage mouse skin carcinogenesis model using DMBA for initiation and TPA for promotion. The investigators suggested that the triterpenoid 21-episerratenediol has potential as an effective cancer chemopreventive agent (Cancer Lett. 2003;196:121–6).
In a separate experiment conducted by this lab, two new serratane-type triterpenoids, 3beta-methoxyserrat-13-en-21-beta-ol and 13-beta,14beta-epoxy-3beta-methoxyserratan-21beta-ol, also isolated from Picea plants, exhibited strong anti-tumor-promoting effects on mouse skin carcinogenesis (Planta Med. 2003;69:1041–7).
This lab also showed that, in a test of the lupane-type triterpenoids isolated from the stem bark of Glochidion zeylanicum as well as synthetic analogues, glochidiol and lup-20(29)-ene-1beta,3beta-diol were the strongest inhibitors of EBV-EA activation induced by TPA. Glochidiol also exhibited the greatest inhibitory effect on skin tumor promotion (Planta Med. 2004;70:1234–6).
Other Anticarcinogenic Actions
In 2005, investigators at the University of North Carolina, Chapel Hill, published a report on cimigenol, an acid- and base-stable triterpenoid found in species such as Cimicifuga racemosa, C. dahurica, and C. japonica. These researchers had previously shown that cimigenol and some of its derivatives had strong inhibitory effects on mouse skin tumor promotion induced by TPA in a two-stage carcinogenesis test. Continuing that previous work, the investigators repeated screens of cimigenol and also tested 15 related compounds as potential anti-tumor promoters by using the in vitro, short-term TPA-induced EBV-EA activation assay (Bioorg. Med. Chem. 2005;13:1403–8).
Of these compounds, the researchers found that cimigenol-3,15-dione showed the greatest potency and, in a subsequent two-stage DMBA/TPA carcinogenesis assay, reduced, at 20 weeks, the number of papillomas per mouse to 48% of controls. Both cimigenol and cimigenol-3,15-dione were also nearly as potent as epigallocatechin gallate, a primary constituent of green tea, in terms of anti-tumor initiation activity, as demonstrated in a two-stage carcinogenesis assay of mouse skin tumors induced by peroxynitrite (initiator) and TPA (promoter).
The investigators concluded that these two triterpenoids amply demonstrate anti-tumor promotion as well as anti-tumor initiation and warrant consideration as significant cancer chemopreventive agents (Bioorg. Med. Chem. 2005;13:1403–8).
Protection Against UV
Four triterpenoids isolated from the stems of Styrax japonica were recently found to significantly inhibit matrix metalloproteinase-1 (MMP-1) in primary human skin fibroblasts induced by UV radiation. This finding is significant given the association between the upregulation of MMPs and chronic skin damage (Biol. Pharm. Bull. 2005;28:2003–6).
Previously, some of the same investigators studied the effects of 3,23-dihydroxy-20(29)-lupen-27-oic acid, a triterpenoid derived from Tiarella polyphylla, on the regulation of MMP-1 and type 1 procollagen in UV irradiation of cultured old-age human dermal fibroblasts. The triterpenoid dose-dependently induced regulation of type 1 procollagen and diminished regulation of MMP-1 at the protein level (Arch. Pharm. Res. 2004;27:1060–4).
Other Pharmacologic Actions
Triterpenoids also have been found in Boswellia serrata, an herb used in traditional medicine to treat inflammatory and arthritic conditions (and discussed in this column in November 2006, p. 17).
In a study published in 2000, the primary components and derivatives of Boswellia markedly inhibited TPA-induced increases in skin inflammation, epidermal proliferation, the number of epidermal cell layers, and tumor promotion in DMBA-initiated mice. DNA synthesis in human leukemia HL-60 cells was also shown to be inhibited by the addition of various forms of boswellic acid. The investigators suggest that such findings demonstrate the anticarcinogenic and antitumor properties of the major constituents, including triterpenoids, of this herb (Biofactors 2000;13:225–30).
The anti-inflammatory activity of several triterpenoids suggests the potential for numerous additional medical applications. A study evaluating the mechanism of anti-inflammatory activity displayed by triterpenoids on edema induced in mouse ears and paws, as well as rat skin, revealed that the inhibition of protein kinase C may play a crucial role in facilitating the anti-inflammatory activity of this class of compounds (Eur. J. Pharmacol. 2000;410:69–81).
In another study, several triterpene constituents of Vochysia pacifica Cuatrec, a South American tree used by traditional communities to treat inflammation, skin sores, asthma, and pulmonary congestion, were found to exert mild inhibitory activity on the intracellular target for new anti-inflammatory medications, namely the cAMP phosphodiesterase 4 isozyme (PDE4) (Phytother. Res. 2005;19:75–7).
Some triterpenoids have been documented as irritating (J. Asian Nat. Prod. Res. 2003;5:35–41) and others as toxic, which is not unexpected as these compounds comprise the primary constituent class in the volatile oils of plants. Given the breadth of this biochemical class, it is expected that some members would be toxic and others safe and beneficial to human health, such as the triterpenoid saponin glycyrrhizin, derived from licorice root (and featured in this column in March 2007, p. 24, and April 2007, p. 30). Triterpenoid saponins, or sapogenins, are used in some emulsifiers, including some Estée Lauder products, for their capacity to confer antifungal, anti-inflammatory, antimicrobial, and adaptogenic activity.
Conclusion
As we continue to explore botanical sources for medical and cosmetic purposes, we will learn more about the numerous triterpenoids found in plants. This class of biochemical compounds typically receives less attention than polyphenols in discussions of the most potent herbal ingredients used in dermatology, but the considerable potential of triterpenoids to be used in a broad range of cutaneous applications is gradually becoming appreciated.
Triterpenoids, to which squalene is the immediate biologic precursor, include steroids and, thus, sterols, and represent the largest group of terpenoids, the most abundant group of botanical constituents and the most common ingredient class found in volatile oils. Consequently, triterpenoids appear in numerous botanical products with traditional and modern applications to dermatology, such as Centella asiatica (gotu kola) and propolis.
Indeed, the naturally occurring triterpenoids, oleanolic acid and ursolic acid, are known to confer anticarcinogenic and anti-inflammatory effects in certain cells (Exp. Dermatol. 2006;15:66–73). Ursolic acid and the natural triterpenoid erythrodiol have also been found to be effective in a multiple-dose 12-O-tetradecanoylphorbol-13-acetate (TPA) model of chronic dermal inflammation (Eur. J. Pharmacol. 1997;334:103–5).
Although triterpenoids are not as prevalent in as many of the highly touted herbal sources as polyphenols, this group of compounds is gaining increased attention for its anti-inflammatory and anti-tumor-promoting activity. In one trial, investigators studying the triterpenoids oleanolic acid and ursolic acid found that the former induced the differentiation of keratinocytes through peroxisome proliferator-activated receptor (PPAR)-α activation. In addition, topical application of oleanolic acid improved the recovery of epidermal permeability barrier function and increased ceramides in epidermis (Exp. Dermatol. 2006;15:66–73).
The preponderance of data on triterpenoids, though, points to the anti-tumor-promoting capacity of this copious botanical class of compounds.
Anti-Tumor-Promoting Actions
In a study designed to identify potential anti-tumor promoters, investigators screened 21 cucurbitane triterpenoids using an in vitro assay system, and found that several of the compounds significantly inhibited Epstein-Barr virus (EBV) activation induced by the tumor promoter TPA.
These compounds were scandenoside R6, 23,24-dihydrocucurbitacin F, 25-acetyl-23,24-dihydrocucurbitacin F, 2-O-beta-D-glucopyranosyl-23,24-dihydrocucurbitacin F, and cucurbitacin F. Two triterpenoids, 23,24-dihydrocucurbitacin F and 2-O-beta-D-glucopyranosyl-23,24-dihydrocucurbitacin F, also displayed significant activity against skin tumor promotion in an in vivo two-stage murine carcinogenesis model (Biol. Pharm. Bull. 1994;17:668–71).
A later in vitro study conducted by the same lab to identify anti-tumor promoters considered 23 triterpenoid hydrocarbons isolated from ferns. Significant inhibitory activity against EBV induced by TPA was exhibited by hop-17(21)-ene, neohop-13(18)-ene, neohop-12-ene, taraxerane, multiflor-9(11)-ene, multiflor-8-ene, glutin-5(10)-ene, and taraxastane. In a two-stage in vivo murine carcinogenesis model using 7,12-dimethylbenz[a]anthracene (DMBA) for initiation and TPA for promotion, hop-17(21)-ene and neohop-13(18)-ene displayed significant anti-tumor promoting effects on mouse skin (Biol. Pharm. Bull. 1996;19:962–5).
Three years later, some of the same investigators, studying triterpenoids derived from Taraxacum japonicum (Compositae) roots, found that taraxasterol and taraxerol significantly inhibited the effects of TPA-induced Epstein-Barr virus early antigen (EBV-EA) induction, which is a preliminary in vitro screening approach to identifying anti-tumor-promoting agents. These compounds also exhibited potent anti-tumor-promoting activity in the two-stage murine skin carcinogenesis model initiated by DMBA and promoted by TPA (Biol. Pharm. Bull. 1999;22:606–10).
In a study from Osaka (Japan) University of Pharmaceutical Sciences, seven serratane-type triterpenoids isolated from different Picea species all exhibited potent inhibitory effects on EBV-EA activation induced by TPA, and did so more strongly than oleanolic acid. In addition, 13alpha,14alpha-epoxy-3beta-methoxyserratan-21beta-ol displayed significant anti-tumor-promoting activity in the in vivo two-stage murine carcinogenesis model (Cancer Lett. 2001;172:119–26).
The same lab subsequently studied 11 serratane-type triterpenoids isolated from various Picea species and three synthetic analogues for their potential inhibitory effects on EBV-EA activation induced by TPA. That study yielded more corroborative findings, as several of the compounds showed potent inhibitory activity, again more strongly than the oleanolic control, including 21-episerratenediol, serratenediol, diepiserratenediol, 3-beta-hydroxyserrat-14-en-21-one, and 3-alpha-methoxy-21-beta-hydroxyserrat-14-en-16-one. Furthermore, no cytotoxicity was associated with these compounds.
Of these triterpenoids, 21-episerratenediol was found to demonstrate significant inhibitory effects on skin tumor promotion in the in vivo two-stage mouse skin carcinogenesis model using DMBA for initiation and TPA for promotion. The investigators suggested that the triterpenoid 21-episerratenediol has potential as an effective cancer chemopreventive agent (Cancer Lett. 2003;196:121–6).
In a separate experiment conducted by this lab, two new serratane-type triterpenoids, 3beta-methoxyserrat-13-en-21-beta-ol and 13-beta,14beta-epoxy-3beta-methoxyserratan-21beta-ol, also isolated from Picea plants, exhibited strong anti-tumor-promoting effects on mouse skin carcinogenesis (Planta Med. 2003;69:1041–7).
This lab also showed that, in a test of the lupane-type triterpenoids isolated from the stem bark of Glochidion zeylanicum as well as synthetic analogues, glochidiol and lup-20(29)-ene-1beta,3beta-diol were the strongest inhibitors of EBV-EA activation induced by TPA. Glochidiol also exhibited the greatest inhibitory effect on skin tumor promotion (Planta Med. 2004;70:1234–6).
Other Anticarcinogenic Actions
In 2005, investigators at the University of North Carolina, Chapel Hill, published a report on cimigenol, an acid- and base-stable triterpenoid found in species such as Cimicifuga racemosa, C. dahurica, and C. japonica. These researchers had previously shown that cimigenol and some of its derivatives had strong inhibitory effects on mouse skin tumor promotion induced by TPA in a two-stage carcinogenesis test. Continuing that previous work, the investigators repeated screens of cimigenol and also tested 15 related compounds as potential anti-tumor promoters by using the in vitro, short-term TPA-induced EBV-EA activation assay (Bioorg. Med. Chem. 2005;13:1403–8).
Of these compounds, the researchers found that cimigenol-3,15-dione showed the greatest potency and, in a subsequent two-stage DMBA/TPA carcinogenesis assay, reduced, at 20 weeks, the number of papillomas per mouse to 48% of controls. Both cimigenol and cimigenol-3,15-dione were also nearly as potent as epigallocatechin gallate, a primary constituent of green tea, in terms of anti-tumor initiation activity, as demonstrated in a two-stage carcinogenesis assay of mouse skin tumors induced by peroxynitrite (initiator) and TPA (promoter).
The investigators concluded that these two triterpenoids amply demonstrate anti-tumor promotion as well as anti-tumor initiation and warrant consideration as significant cancer chemopreventive agents (Bioorg. Med. Chem. 2005;13:1403–8).
Protection Against UV
Four triterpenoids isolated from the stems of Styrax japonica were recently found to significantly inhibit matrix metalloproteinase-1 (MMP-1) in primary human skin fibroblasts induced by UV radiation. This finding is significant given the association between the upregulation of MMPs and chronic skin damage (Biol. Pharm. Bull. 2005;28:2003–6).
Previously, some of the same investigators studied the effects of 3,23-dihydroxy-20(29)-lupen-27-oic acid, a triterpenoid derived from Tiarella polyphylla, on the regulation of MMP-1 and type 1 procollagen in UV irradiation of cultured old-age human dermal fibroblasts. The triterpenoid dose-dependently induced regulation of type 1 procollagen and diminished regulation of MMP-1 at the protein level (Arch. Pharm. Res. 2004;27:1060–4).
Other Pharmacologic Actions
Triterpenoids also have been found in Boswellia serrata, an herb used in traditional medicine to treat inflammatory and arthritic conditions (and discussed in this column in November 2006, p. 17).
In a study published in 2000, the primary components and derivatives of Boswellia markedly inhibited TPA-induced increases in skin inflammation, epidermal proliferation, the number of epidermal cell layers, and tumor promotion in DMBA-initiated mice. DNA synthesis in human leukemia HL-60 cells was also shown to be inhibited by the addition of various forms of boswellic acid. The investigators suggest that such findings demonstrate the anticarcinogenic and antitumor properties of the major constituents, including triterpenoids, of this herb (Biofactors 2000;13:225–30).
The anti-inflammatory activity of several triterpenoids suggests the potential for numerous additional medical applications. A study evaluating the mechanism of anti-inflammatory activity displayed by triterpenoids on edema induced in mouse ears and paws, as well as rat skin, revealed that the inhibition of protein kinase C may play a crucial role in facilitating the anti-inflammatory activity of this class of compounds (Eur. J. Pharmacol. 2000;410:69–81).
In another study, several triterpene constituents of Vochysia pacifica Cuatrec, a South American tree used by traditional communities to treat inflammation, skin sores, asthma, and pulmonary congestion, were found to exert mild inhibitory activity on the intracellular target for new anti-inflammatory medications, namely the cAMP phosphodiesterase 4 isozyme (PDE4) (Phytother. Res. 2005;19:75–7).
Some triterpenoids have been documented as irritating (J. Asian Nat. Prod. Res. 2003;5:35–41) and others as toxic, which is not unexpected as these compounds comprise the primary constituent class in the volatile oils of plants. Given the breadth of this biochemical class, it is expected that some members would be toxic and others safe and beneficial to human health, such as the triterpenoid saponin glycyrrhizin, derived from licorice root (and featured in this column in March 2007, p. 24, and April 2007, p. 30). Triterpenoid saponins, or sapogenins, are used in some emulsifiers, including some Estée Lauder products, for their capacity to confer antifungal, anti-inflammatory, antimicrobial, and adaptogenic activity.
Conclusion
As we continue to explore botanical sources for medical and cosmetic purposes, we will learn more about the numerous triterpenoids found in plants. This class of biochemical compounds typically receives less attention than polyphenols in discussions of the most potent herbal ingredients used in dermatology, but the considerable potential of triterpenoids to be used in a broad range of cutaneous applications is gradually becoming appreciated.
Mahonia
Mahonia aquifolium, also known as Oregon grape root, belongs to the Berberidaceae or barberry family. This evergreen shrub, native to the American northwest and adjacent areas of Canada, has been used in folk medicine to treat chronic eruptions and various rashes, especially those containing pustules or resulting from consumption of fatty foods (Dermatol. Ther. 2003;16:106–13).
In numerous investigations, Oregon grape root has displayed a wide range of biologic activities, including antioxidant, antimicrobial, and antimutagenic properties. Although this column will focus on the Mahonia aquifolium species, it is worth noting that Mahonia bealei (also of the Berberidaceae family), native to China, exhibits anti-influenza effects in vitro (Zhong Yao Cai. 2003;26:29–30).
Research on the extract of the bark of Mahonia aquifolium has indicated that its primary bioactive characteristic is the inhibition of lipid peroxidation, and that its main constituents are the alkaloids berberine, berbamine, and oxyacanthine (Planta Med. 1994;60:421–4).
Mahonia aquifolium bark extract has been shown to inhibit keratinocyte growth. In one study, berberine was as effective as the mahonia extract at inhibiting cell growth, while berbamine and oxyacanthine, the benzylisoquinoline alkaloid constituents of mahonia, were three times as effective at cell growth suppression (Planta Med. 1995;61:74–5).
Berberine-containing herbs have been used in folk medicine to relieve neonatal jaundice (Comp. Med. East West 1977;5:161–8), as anti-inflammatory agents (for lumbago and rheumatism), and as antinociceptive and antipyretic medications (Life Sci. 2002;72:645–57; J. Ethnopharmacol. 1998;59:211–5). Further, researchers studying the use of berberine as an antiacne medication in Japanese Kampoh (Japanese herbal medicine based on Chinese methods) found that the alkaloid inhibited lipogenesis in hamster sebaceous glands by 63% (Skin Pharmacol. 1993;6:56–60).
Antimicrobial Actions
In a study more than a decade ago, researchers screened 100 methanolic plant extracts for antifungal activity against nine species of fungi. In all, 81 of the extracts had some antifungal activity, and 30 extracts demonstrated activity against at least four of the fungal species assayed. Mahonia was one of six extracts showing the greatest antifungal activity (J. Ethnopharmacol. 1994;44:157–69).
In a more recent study, investigators evaluated the activity of Mahonia aquifolium stem bark extract and three of its constituents—berberine, palmatine, and jatrorrhizine—against various dermatophytes and two Candida species of human origin. Jatrorrhizine was the most effective against all the fungi tested. Investigators concluded that this component of mahonia would be more suitable than berberine, palmatine, and the crude extract for further investigation as a potential antifungal agent (Phytother Res. 2003;17:834–7).
In vitro antimicrobial activity was also exhibited by the crude extract of Mahonia aquifolium stem bark and its two main protoberberine alkaloids, berberine and jatrorrhizine, in a wide-ranging evaluation of antibacterial and antifungal activity.
The crude extract and key constituents displayed various levels of activity against 20 strains of coagulase-negative staphylococci, 20 strains of Propionibacterium acnes isolated from skin lesions of patients with severe acne, and 20 strains of Candida isolated from chronic vulvovaginal candidoses. Investigators concluded that the results buttressed the traditional use of Mahonia aquifolium for the treatment of localized skin and mucosal infections, and that the herb warrants consideration for inclusion in formulations to treat acne and chronic yeast infections (Phytother. Res. 2004;18:674–6).
Evidence of berberine's antimicrobial activity against several bacterial and fungal species has been gathering for several years (Folia Microbiol. 1999;44:164–6; Planta Med. 1997;63:196–8; J. Pharm. Sci. 1994;83:404–6; Canad. J. Microbiol. 1969;15:1067–76).
Antitumor Activity
Berberine has been shown to induce apoptosis in promyelocytic leukemia HL-60 and 3T3 fibroblast cells (Arch. Pharmacol. 1996;354:102–6; Cancer Lett. 1995;93:193–200), and protoberberines have exhibited significant toxicity against topoisomerases (Biochem. Pharmacol. 1998;56:1157–66).
Berberine, which is also the main alkaloid constituent of goldenseal, an herb used medically in eyewash and skin lotion formulations, was evaluated recently for its photochemical interactions with different solvents and potential phototoxicity to HaCaT keratinocytes. The alkaloid was a weak photosensitizer in water, but capable of generating superoxide anions and other radicals in a nonpolar setting. Significant reductions in cell viability and simultaneous elevation in DNA damage were observed in HaCaT keratinocytes exposed to UVA in the presence of berberine. The investigators concluded that exposure to the sun or to artificial UVA is contraindicated in people using topical products containing berberine (Chem. Res. Toxicol. 2001;14:1529–34).
In a study of the antimutagenic activity of crude extract fractions of the bark of Mahonia aquifolium against the common direct-acting mutagen acridine orange, investigators found that while antimutagenic properties were associated with both bis-benzylisoquinoline and protoberberine alkaloid fractions, only the protoberberine derivatives, jatrorrhizine and berberine, exhibited significant concentration-dependent inhibitory activity against the mutagen.
This was particularly true of berberine, which was threefold stronger than jatrorrhizine. In fact, even at very low doses, berberine suppressed the acridine orange-induced mutagenicity and consistently demonstrated the highest cytotoxicity among the mahonia components tested (BMC Complement Altern. Med. 2002;2:2).
Other Actions
In a chemical structural study of three alkaloids isolated from Mahonia aquifolium (berberine, jatrorrhizine, and magnoflorine), the free phenolic group-bearing alkaloids (jatrorrhizine and magnoflorine) exhibited a greater capacity to scavenge peroxyl radicals, which the investigators attributed to higher lipophilicity (Bioorg. Med. Chem. 2004;12:4709–15). Nevertheless, berberine is one of the primary active ingredients in mahonia that is consistently identified for study.
Photochemical reactions and sensitivity are particularly relevant, as a recent study showed that irradiation of berberine in oxygenated dimethyl sulfoxide solvent generated the formation of superoxide anion radicals and singlet oxygen.
Other protoberberinium salts—palmatine and jatrorrhizine—were associated with significantly less photochemical generation of reactive oxygen species. Nevertheless, the investigators concluded that UVA-induced photochemical reactions of protoberberinium salts, which have been shown to exhibit antibacterial, antimalarial, and antitumor activity, warrant attention, particularly in their use for treating skin disorders (Phytother Res. 2004;18:640–6).
Psoriasis
By far, psoriasis is the dermatologic condition most associated with treatment using Mahonia aquifolium. Traditional and alternative treatments, as well as a growing body of research, bear this out.
In one study, investigators tested four protoberberine alkaloid extracts of Mahonia aquifolium (berberine, oxyberberine, jatrorrhizine, columbamine), as well as two aporphine alkaloid extracts of the herb (magnoflorine and corytuberine), for their ability to inhibit lipoxygenase, the metabolism of which contributes to psoriasis pathogenesis.
Oxyberberine, corytuberine, and columbamine were significantly better inhibitors than the remaining alkaloids. Lipoxygenase inhibition was found to be commensurate with lipid antioxidant activity. The authors concluded that the efficacy of Mahonia aquifolium for the treatment of psoriasis can be at least partially ascribed to the lipoxygenase inhibition imparted by the herb's alkaloid constituents (Planta Med. 1995;61:372–3).
In another study evaluating the capacity of Mahonia aquifolium compounds to inhibit lipoxygenase, the same team of investigators tested six bis-benzylisoquinoline (BBIQ) alkaloid constituents (oxyacanthine, armoline, baluchistine, berbamine, obamegine, and aquifoline) and found that berbamine and oxyacanthine were the most potent inhibitors, also significantly hampering lipid peroxidation. The researchers again suggested that the inhibition of lipoxygenase by these Mahonia aquifolium components may account for therapeutic effects of the plant extract, particularly when it is used to treat psoriasis (Pharmazie. 1996;51:758–61).
In a monograph published in 2005, three open-label clinical trials of Mahonia aquifolium 10% topical cream for treatment of psoriasis were discussed. The first study, which evaluated the safety of the herb in 39 patients treated for 12 weeks, revealed statistically significant increases in Psoriasis Area and Severity Index (PASI) and Dermatology Life Quality Index (DLQI) scores after 4 weeks of treatment that continued up to 1 month after treatment ended.
The second study examined 32 psoriasis patients with mild to moderate bilateral presentations treated for up to 6 months with mahonia on one side of the body and a standard psoriasis formulation, i.e., calcipotriene ointment (Dovonex), on the other. The herbal treatment was considered effective, with 84% of patients reporting a good to excellent response and 63% of patients rating Mahonia aquifolium equal to or better than the standard preparation.
Similarly, the third trial, an observational study of 33 patients with mild to moderate bilateral psoriasis treated for 1 month, showed that patients improved after 1 week of therapy, with mahonia performing as well as or better than the vehicle-treated side.
The authors suggested that these findings by numerous researchers in several countries show Mahonia aquifolium to be safe and effective as a treatment for mild to moderate psoriasis (Am. J. Ther. 2005;12:398–406).
Conclusions
In addition to a long history of traditional folk use of Mahonia aquifolium, there is an expanding track record of modern use of this dynamic herb for several dermatologic indications, especially psoriasis. Mahonia's reputation as a long-time natural remedy, as well as its status in the sanctioned dermatologic armamentarium, positions this botanical as an important ingredient in a broad array of accepted medications and over-the-counter preparations.
In terms of psoriasis treatment, Mahonia aquifolium appears to belong among the various treatments considered for the mild to moderate manifestation of this recalcitrant condition.
Mahonia aquifolium, also known as Oregon grape root, belongs to the Berberidaceae or barberry family. This evergreen shrub, native to the American northwest and adjacent areas of Canada, has been used in folk medicine to treat chronic eruptions and various rashes, especially those containing pustules or resulting from consumption of fatty foods (Dermatol. Ther. 2003;16:106–13).
In numerous investigations, Oregon grape root has displayed a wide range of biologic activities, including antioxidant, antimicrobial, and antimutagenic properties. Although this column will focus on the Mahonia aquifolium species, it is worth noting that Mahonia bealei (also of the Berberidaceae family), native to China, exhibits anti-influenza effects in vitro (Zhong Yao Cai. 2003;26:29–30).
Research on the extract of the bark of Mahonia aquifolium has indicated that its primary bioactive characteristic is the inhibition of lipid peroxidation, and that its main constituents are the alkaloids berberine, berbamine, and oxyacanthine (Planta Med. 1994;60:421–4).
Mahonia aquifolium bark extract has been shown to inhibit keratinocyte growth. In one study, berberine was as effective as the mahonia extract at inhibiting cell growth, while berbamine and oxyacanthine, the benzylisoquinoline alkaloid constituents of mahonia, were three times as effective at cell growth suppression (Planta Med. 1995;61:74–5).
Berberine-containing herbs have been used in folk medicine to relieve neonatal jaundice (Comp. Med. East West 1977;5:161–8), as anti-inflammatory agents (for lumbago and rheumatism), and as antinociceptive and antipyretic medications (Life Sci. 2002;72:645–57; J. Ethnopharmacol. 1998;59:211–5). Further, researchers studying the use of berberine as an antiacne medication in Japanese Kampoh (Japanese herbal medicine based on Chinese methods) found that the alkaloid inhibited lipogenesis in hamster sebaceous glands by 63% (Skin Pharmacol. 1993;6:56–60).
Antimicrobial Actions
In a study more than a decade ago, researchers screened 100 methanolic plant extracts for antifungal activity against nine species of fungi. In all, 81 of the extracts had some antifungal activity, and 30 extracts demonstrated activity against at least four of the fungal species assayed. Mahonia was one of six extracts showing the greatest antifungal activity (J. Ethnopharmacol. 1994;44:157–69).
In a more recent study, investigators evaluated the activity of Mahonia aquifolium stem bark extract and three of its constituents—berberine, palmatine, and jatrorrhizine—against various dermatophytes and two Candida species of human origin. Jatrorrhizine was the most effective against all the fungi tested. Investigators concluded that this component of mahonia would be more suitable than berberine, palmatine, and the crude extract for further investigation as a potential antifungal agent (Phytother Res. 2003;17:834–7).
In vitro antimicrobial activity was also exhibited by the crude extract of Mahonia aquifolium stem bark and its two main protoberberine alkaloids, berberine and jatrorrhizine, in a wide-ranging evaluation of antibacterial and antifungal activity.
The crude extract and key constituents displayed various levels of activity against 20 strains of coagulase-negative staphylococci, 20 strains of Propionibacterium acnes isolated from skin lesions of patients with severe acne, and 20 strains of Candida isolated from chronic vulvovaginal candidoses. Investigators concluded that the results buttressed the traditional use of Mahonia aquifolium for the treatment of localized skin and mucosal infections, and that the herb warrants consideration for inclusion in formulations to treat acne and chronic yeast infections (Phytother. Res. 2004;18:674–6).
Evidence of berberine's antimicrobial activity against several bacterial and fungal species has been gathering for several years (Folia Microbiol. 1999;44:164–6; Planta Med. 1997;63:196–8; J. Pharm. Sci. 1994;83:404–6; Canad. J. Microbiol. 1969;15:1067–76).
Antitumor Activity
Berberine has been shown to induce apoptosis in promyelocytic leukemia HL-60 and 3T3 fibroblast cells (Arch. Pharmacol. 1996;354:102–6; Cancer Lett. 1995;93:193–200), and protoberberines have exhibited significant toxicity against topoisomerases (Biochem. Pharmacol. 1998;56:1157–66).
Berberine, which is also the main alkaloid constituent of goldenseal, an herb used medically in eyewash and skin lotion formulations, was evaluated recently for its photochemical interactions with different solvents and potential phototoxicity to HaCaT keratinocytes. The alkaloid was a weak photosensitizer in water, but capable of generating superoxide anions and other radicals in a nonpolar setting. Significant reductions in cell viability and simultaneous elevation in DNA damage were observed in HaCaT keratinocytes exposed to UVA in the presence of berberine. The investigators concluded that exposure to the sun or to artificial UVA is contraindicated in people using topical products containing berberine (Chem. Res. Toxicol. 2001;14:1529–34).
In a study of the antimutagenic activity of crude extract fractions of the bark of Mahonia aquifolium against the common direct-acting mutagen acridine orange, investigators found that while antimutagenic properties were associated with both bis-benzylisoquinoline and protoberberine alkaloid fractions, only the protoberberine derivatives, jatrorrhizine and berberine, exhibited significant concentration-dependent inhibitory activity against the mutagen.
This was particularly true of berberine, which was threefold stronger than jatrorrhizine. In fact, even at very low doses, berberine suppressed the acridine orange-induced mutagenicity and consistently demonstrated the highest cytotoxicity among the mahonia components tested (BMC Complement Altern. Med. 2002;2:2).
Other Actions
In a chemical structural study of three alkaloids isolated from Mahonia aquifolium (berberine, jatrorrhizine, and magnoflorine), the free phenolic group-bearing alkaloids (jatrorrhizine and magnoflorine) exhibited a greater capacity to scavenge peroxyl radicals, which the investigators attributed to higher lipophilicity (Bioorg. Med. Chem. 2004;12:4709–15). Nevertheless, berberine is one of the primary active ingredients in mahonia that is consistently identified for study.
Photochemical reactions and sensitivity are particularly relevant, as a recent study showed that irradiation of berberine in oxygenated dimethyl sulfoxide solvent generated the formation of superoxide anion radicals and singlet oxygen.
Other protoberberinium salts—palmatine and jatrorrhizine—were associated with significantly less photochemical generation of reactive oxygen species. Nevertheless, the investigators concluded that UVA-induced photochemical reactions of protoberberinium salts, which have been shown to exhibit antibacterial, antimalarial, and antitumor activity, warrant attention, particularly in their use for treating skin disorders (Phytother Res. 2004;18:640–6).
Psoriasis
By far, psoriasis is the dermatologic condition most associated with treatment using Mahonia aquifolium. Traditional and alternative treatments, as well as a growing body of research, bear this out.
In one study, investigators tested four protoberberine alkaloid extracts of Mahonia aquifolium (berberine, oxyberberine, jatrorrhizine, columbamine), as well as two aporphine alkaloid extracts of the herb (magnoflorine and corytuberine), for their ability to inhibit lipoxygenase, the metabolism of which contributes to psoriasis pathogenesis.
Oxyberberine, corytuberine, and columbamine were significantly better inhibitors than the remaining alkaloids. Lipoxygenase inhibition was found to be commensurate with lipid antioxidant activity. The authors concluded that the efficacy of Mahonia aquifolium for the treatment of psoriasis can be at least partially ascribed to the lipoxygenase inhibition imparted by the herb's alkaloid constituents (Planta Med. 1995;61:372–3).
In another study evaluating the capacity of Mahonia aquifolium compounds to inhibit lipoxygenase, the same team of investigators tested six bis-benzylisoquinoline (BBIQ) alkaloid constituents (oxyacanthine, armoline, baluchistine, berbamine, obamegine, and aquifoline) and found that berbamine and oxyacanthine were the most potent inhibitors, also significantly hampering lipid peroxidation. The researchers again suggested that the inhibition of lipoxygenase by these Mahonia aquifolium components may account for therapeutic effects of the plant extract, particularly when it is used to treat psoriasis (Pharmazie. 1996;51:758–61).
In a monograph published in 2005, three open-label clinical trials of Mahonia aquifolium 10% topical cream for treatment of psoriasis were discussed. The first study, which evaluated the safety of the herb in 39 patients treated for 12 weeks, revealed statistically significant increases in Psoriasis Area and Severity Index (PASI) and Dermatology Life Quality Index (DLQI) scores after 4 weeks of treatment that continued up to 1 month after treatment ended.
The second study examined 32 psoriasis patients with mild to moderate bilateral presentations treated for up to 6 months with mahonia on one side of the body and a standard psoriasis formulation, i.e., calcipotriene ointment (Dovonex), on the other. The herbal treatment was considered effective, with 84% of patients reporting a good to excellent response and 63% of patients rating Mahonia aquifolium equal to or better than the standard preparation.
Similarly, the third trial, an observational study of 33 patients with mild to moderate bilateral psoriasis treated for 1 month, showed that patients improved after 1 week of therapy, with mahonia performing as well as or better than the vehicle-treated side.
The authors suggested that these findings by numerous researchers in several countries show Mahonia aquifolium to be safe and effective as a treatment for mild to moderate psoriasis (Am. J. Ther. 2005;12:398–406).
Conclusions
In addition to a long history of traditional folk use of Mahonia aquifolium, there is an expanding track record of modern use of this dynamic herb for several dermatologic indications, especially psoriasis. Mahonia's reputation as a long-time natural remedy, as well as its status in the sanctioned dermatologic armamentarium, positions this botanical as an important ingredient in a broad array of accepted medications and over-the-counter preparations.
In terms of psoriasis treatment, Mahonia aquifolium appears to belong among the various treatments considered for the mild to moderate manifestation of this recalcitrant condition.
Mahonia aquifolium, also known as Oregon grape root, belongs to the Berberidaceae or barberry family. This evergreen shrub, native to the American northwest and adjacent areas of Canada, has been used in folk medicine to treat chronic eruptions and various rashes, especially those containing pustules or resulting from consumption of fatty foods (Dermatol. Ther. 2003;16:106–13).
In numerous investigations, Oregon grape root has displayed a wide range of biologic activities, including antioxidant, antimicrobial, and antimutagenic properties. Although this column will focus on the Mahonia aquifolium species, it is worth noting that Mahonia bealei (also of the Berberidaceae family), native to China, exhibits anti-influenza effects in vitro (Zhong Yao Cai. 2003;26:29–30).
Research on the extract of the bark of Mahonia aquifolium has indicated that its primary bioactive characteristic is the inhibition of lipid peroxidation, and that its main constituents are the alkaloids berberine, berbamine, and oxyacanthine (Planta Med. 1994;60:421–4).
Mahonia aquifolium bark extract has been shown to inhibit keratinocyte growth. In one study, berberine was as effective as the mahonia extract at inhibiting cell growth, while berbamine and oxyacanthine, the benzylisoquinoline alkaloid constituents of mahonia, were three times as effective at cell growth suppression (Planta Med. 1995;61:74–5).
Berberine-containing herbs have been used in folk medicine to relieve neonatal jaundice (Comp. Med. East West 1977;5:161–8), as anti-inflammatory agents (for lumbago and rheumatism), and as antinociceptive and antipyretic medications (Life Sci. 2002;72:645–57; J. Ethnopharmacol. 1998;59:211–5). Further, researchers studying the use of berberine as an antiacne medication in Japanese Kampoh (Japanese herbal medicine based on Chinese methods) found that the alkaloid inhibited lipogenesis in hamster sebaceous glands by 63% (Skin Pharmacol. 1993;6:56–60).
Antimicrobial Actions
In a study more than a decade ago, researchers screened 100 methanolic plant extracts for antifungal activity against nine species of fungi. In all, 81 of the extracts had some antifungal activity, and 30 extracts demonstrated activity against at least four of the fungal species assayed. Mahonia was one of six extracts showing the greatest antifungal activity (J. Ethnopharmacol. 1994;44:157–69).
In a more recent study, investigators evaluated the activity of Mahonia aquifolium stem bark extract and three of its constituents—berberine, palmatine, and jatrorrhizine—against various dermatophytes and two Candida species of human origin. Jatrorrhizine was the most effective against all the fungi tested. Investigators concluded that this component of mahonia would be more suitable than berberine, palmatine, and the crude extract for further investigation as a potential antifungal agent (Phytother Res. 2003;17:834–7).
In vitro antimicrobial activity was also exhibited by the crude extract of Mahonia aquifolium stem bark and its two main protoberberine alkaloids, berberine and jatrorrhizine, in a wide-ranging evaluation of antibacterial and antifungal activity.
The crude extract and key constituents displayed various levels of activity against 20 strains of coagulase-negative staphylococci, 20 strains of Propionibacterium acnes isolated from skin lesions of patients with severe acne, and 20 strains of Candida isolated from chronic vulvovaginal candidoses. Investigators concluded that the results buttressed the traditional use of Mahonia aquifolium for the treatment of localized skin and mucosal infections, and that the herb warrants consideration for inclusion in formulations to treat acne and chronic yeast infections (Phytother. Res. 2004;18:674–6).
Evidence of berberine's antimicrobial activity against several bacterial and fungal species has been gathering for several years (Folia Microbiol. 1999;44:164–6; Planta Med. 1997;63:196–8; J. Pharm. Sci. 1994;83:404–6; Canad. J. Microbiol. 1969;15:1067–76).
Antitumor Activity
Berberine has been shown to induce apoptosis in promyelocytic leukemia HL-60 and 3T3 fibroblast cells (Arch. Pharmacol. 1996;354:102–6; Cancer Lett. 1995;93:193–200), and protoberberines have exhibited significant toxicity against topoisomerases (Biochem. Pharmacol. 1998;56:1157–66).
Berberine, which is also the main alkaloid constituent of goldenseal, an herb used medically in eyewash and skin lotion formulations, was evaluated recently for its photochemical interactions with different solvents and potential phototoxicity to HaCaT keratinocytes. The alkaloid was a weak photosensitizer in water, but capable of generating superoxide anions and other radicals in a nonpolar setting. Significant reductions in cell viability and simultaneous elevation in DNA damage were observed in HaCaT keratinocytes exposed to UVA in the presence of berberine. The investigators concluded that exposure to the sun or to artificial UVA is contraindicated in people using topical products containing berberine (Chem. Res. Toxicol. 2001;14:1529–34).
In a study of the antimutagenic activity of crude extract fractions of the bark of Mahonia aquifolium against the common direct-acting mutagen acridine orange, investigators found that while antimutagenic properties were associated with both bis-benzylisoquinoline and protoberberine alkaloid fractions, only the protoberberine derivatives, jatrorrhizine and berberine, exhibited significant concentration-dependent inhibitory activity against the mutagen.
This was particularly true of berberine, which was threefold stronger than jatrorrhizine. In fact, even at very low doses, berberine suppressed the acridine orange-induced mutagenicity and consistently demonstrated the highest cytotoxicity among the mahonia components tested (BMC Complement Altern. Med. 2002;2:2).
Other Actions
In a chemical structural study of three alkaloids isolated from Mahonia aquifolium (berberine, jatrorrhizine, and magnoflorine), the free phenolic group-bearing alkaloids (jatrorrhizine and magnoflorine) exhibited a greater capacity to scavenge peroxyl radicals, which the investigators attributed to higher lipophilicity (Bioorg. Med. Chem. 2004;12:4709–15). Nevertheless, berberine is one of the primary active ingredients in mahonia that is consistently identified for study.
Photochemical reactions and sensitivity are particularly relevant, as a recent study showed that irradiation of berberine in oxygenated dimethyl sulfoxide solvent generated the formation of superoxide anion radicals and singlet oxygen.
Other protoberberinium salts—palmatine and jatrorrhizine—were associated with significantly less photochemical generation of reactive oxygen species. Nevertheless, the investigators concluded that UVA-induced photochemical reactions of protoberberinium salts, which have been shown to exhibit antibacterial, antimalarial, and antitumor activity, warrant attention, particularly in their use for treating skin disorders (Phytother Res. 2004;18:640–6).
Psoriasis
By far, psoriasis is the dermatologic condition most associated with treatment using Mahonia aquifolium. Traditional and alternative treatments, as well as a growing body of research, bear this out.
In one study, investigators tested four protoberberine alkaloid extracts of Mahonia aquifolium (berberine, oxyberberine, jatrorrhizine, columbamine), as well as two aporphine alkaloid extracts of the herb (magnoflorine and corytuberine), for their ability to inhibit lipoxygenase, the metabolism of which contributes to psoriasis pathogenesis.
Oxyberberine, corytuberine, and columbamine were significantly better inhibitors than the remaining alkaloids. Lipoxygenase inhibition was found to be commensurate with lipid antioxidant activity. The authors concluded that the efficacy of Mahonia aquifolium for the treatment of psoriasis can be at least partially ascribed to the lipoxygenase inhibition imparted by the herb's alkaloid constituents (Planta Med. 1995;61:372–3).
In another study evaluating the capacity of Mahonia aquifolium compounds to inhibit lipoxygenase, the same team of investigators tested six bis-benzylisoquinoline (BBIQ) alkaloid constituents (oxyacanthine, armoline, baluchistine, berbamine, obamegine, and aquifoline) and found that berbamine and oxyacanthine were the most potent inhibitors, also significantly hampering lipid peroxidation. The researchers again suggested that the inhibition of lipoxygenase by these Mahonia aquifolium components may account for therapeutic effects of the plant extract, particularly when it is used to treat psoriasis (Pharmazie. 1996;51:758–61).
In a monograph published in 2005, three open-label clinical trials of Mahonia aquifolium 10% topical cream for treatment of psoriasis were discussed. The first study, which evaluated the safety of the herb in 39 patients treated for 12 weeks, revealed statistically significant increases in Psoriasis Area and Severity Index (PASI) and Dermatology Life Quality Index (DLQI) scores after 4 weeks of treatment that continued up to 1 month after treatment ended.
The second study examined 32 psoriasis patients with mild to moderate bilateral presentations treated for up to 6 months with mahonia on one side of the body and a standard psoriasis formulation, i.e., calcipotriene ointment (Dovonex), on the other. The herbal treatment was considered effective, with 84% of patients reporting a good to excellent response and 63% of patients rating Mahonia aquifolium equal to or better than the standard preparation.
Similarly, the third trial, an observational study of 33 patients with mild to moderate bilateral psoriasis treated for 1 month, showed that patients improved after 1 week of therapy, with mahonia performing as well as or better than the vehicle-treated side.
The authors suggested that these findings by numerous researchers in several countries show Mahonia aquifolium to be safe and effective as a treatment for mild to moderate psoriasis (Am. J. Ther. 2005;12:398–406).
Conclusions
In addition to a long history of traditional folk use of Mahonia aquifolium, there is an expanding track record of modern use of this dynamic herb for several dermatologic indications, especially psoriasis. Mahonia's reputation as a long-time natural remedy, as well as its status in the sanctioned dermatologic armamentarium, positions this botanical as an important ingredient in a broad array of accepted medications and over-the-counter preparations.
In terms of psoriasis treatment, Mahonia aquifolium appears to belong among the various treatments considered for the mild to moderate manifestation of this recalcitrant condition.
Boldine
Boldo (Peumus boldus Mol.) is a slow-growing, shrubby evergreen tree native to the Chilean and Peruvian Andes. It is also found in Morocco and other parts of North Africa, and is cultivated in Europe. The plant has traditionally been used in South American folk medicine, particularly in Chile, Peru, and Brazil, to treat a wide range of conditions of the liver, bowel, and gallbladder (Pharmacol. Res. 1994;29:1–12).
The primary active constituent identified in the tree is boldine, a simple aporphine alkaloid. Several aporphine alkaloids, which are secondary metabolites, are found in boldo leaves, with boldine being the most abundant (Curr. Med. Chem. Anticancer Agents 2005;5:173–82). Boldine is extracted from the leaves and bark of the tree (Phytother. Res. 2000;14:339–43; Pharmazie 2001;56:242–3).
In Germany and other European countries, the boldo plant is used as a medicinal. It is the subject of a German Commission E monograph that details the acceptable uses of the plant as an herbal drug for liver, gallbladder, and gastric conditions (Blumenthal M., et al. [eds.] The Complete German Commission E Monographs: Therapeutic Guide to Herbal Medicines. Austin, Tex.: American Botanical Council and Boston: Integrative Medicine Communications, 1998, pp. 93–4).
Boldine is used worldwide in homeopathic and herbal medicine, and boldine extract is widely acknowledged as a viable herbal remedy in several pharmacopoeias (Chem. Biol. Interact. 2006;159:1–17; Pharmacol. Res. 1994;29:1–12). Indeed, boldine has been demonstrated to possess antioxidant activity in biologic as well as nonbiologic systems, and it has emerged as an ingredient of great interest for its potential in the treatment of free radical-mediated damage or conditions (Pharmacol. Res. 1994;29:1–12).
Antioxidant Actions
Boldine is now considered one of the strongest natural antioxidants (Chem. Biol. Interact. 2006;159:1–17).
In the early 1990s, the traditional use of Peumus boldus extract prompted a team of researchers to validate some of its therapeutic properties. They found that boldine imparted significant protection in vitro against tert-butyl hydroperoxide-induced toxicity in isolated rat hepatocytes, and in vivo against carbon tetrachloride-induced hepatotoxicity in mice. A test in rats with carrageenan-induced edema also revealed significant and dose-dependent anti-inflammatory effects (Planta Med. 1991;57:110–5). The free radical-scavenging and hepatoprotective properties of this natural compound are now considered well established (Phytother. Res. 2000;14:254–60).
A 2001 study demonstrated that boldine imparts chemoprotective activity in murine liver, reducing the metabolic activation of drug-metabolizing enzymes as well as chemical mutagens (Pharmazie 2001;56:242–3).
Alkaloids semisynthesized from boldine have also been shown to inhibit activity against reactive oxygen species and are believed to represent a potential therapy for inflammatory disorders involving production of reactive oxygen species (Chem. Pharm. Bull. [Tokyo] 2004;52:696–9).
In a study in mice, boldine showed significant antioxidant activity, decreasing the oxidation of low-density lipoprotein. It also lessened atherosclerotic lesion formation in LDL receptor-deficient mice that were fed an atherogenic diet. The authors believe that antioxidant capacity, coupled with the traditional tolerance to boldine in humans, renders it a suitable alternative to vitamin E (Atherosclerosis 2004;173:203–10).
More evidence of boldine's antioxidant effects emerged from a study in which it protected intact red blood cells against hemolytic damage caused by the free radical initiator 2,2′-azobis-(2-amidinopropane) (AAPH). The effect was concentration dependent and occurred whether the herb was added simultaneously with, or 1 hour before, AAPH. Erythrocytes previously incubated with AAPH for 2 hours were largely unaffected by the addition of boldine. The investigators concluded that boldine had significant time-dependent cytoprotective as well as antioxidant activity (Phytother. Res. 2000;14:339–43).
It is noteworthy that boldine is found in plants other than the Chilean boldo. In a study of boldine and other aporphine alkaloids isolated from Lindera angustifolia Chen, a Chinese medicinal plant used for edema and rheumatic pain, the extract exhibited significant free radical-scavenging activity against 2,2-diphenyl-1-picrylhydrazyl. It also showed antinociceptive properties, which are thought to be associated with the capacity to scavenge free radicals (J. Ethnopharmacol. 2006;106:408–13).
Other Therapeutic Actions
Boldine has been shown to exert cytoprotective, anti-tumor promoting, anti-inflammatory, antidiabetic, and antiatherogenic activities, all of which may arise from its free radical-scavenging properties. This potent alkaloid also has been shown to confer significant pharmacologic benefit not related to oxidative stress, such as antitrypanocidal, vasorelaxing, immuno- and neuromodulatory, and cholagogic and/or choleretic activity (Chem. Biol. Interact. 2006;159:1–17).
In a study of carrageenan-induced edema in guinea pigs, boldine exhibited dose-dependent anti-inflammatory activity. It also acted against bacterial pyrogen-induced hyperthermia in rabbits. In addition, an in vitro arm of the same study revealed that boldine inhibited prostaglandin biosynthesis, to which investigators attributed the in vivo anti-inflammatory and antipyretic activities of boldine (Agents Actions 1994;42:114–7).
Boldine is contraindicated in people who have kidney disease, women who are pregnant or breast-feeding, and patients with liver bile duct obstruction or severe liver disease (Brinker F. Herb Contraindications and Drug Interactions. Sandy, Ore.: Eclectic Medical Publications, 1997, p. 26).
Photoprotective Action
In a recent study with the most direct dermatologic implications, boldine was shown to be photostable, with its antioxidative capacity remaining intact, thereby allowing the compound to confer photoprotection (J. Photochem. Photobiol. B 2005;80:65–9). Furthermore, in vitro tests of compounds extracted from lichens and the boldo tree revealed that their ultraviolet filtering power was similar to, or better than, that of octylmethoxycinnamate, suggesting their potential usefulness in sunscreen formulations (J. Photochem. Photobiol. B 2002;68:133–9).
Conclusions
Natural antioxidants are too plentiful, and the number under active investigation for medical and cosmetic uses too copious, to suggest that any one compound is the antioxidant du jour. That said, boldine has been studied with increasing frequency over the past 15 years, after a long history of use in folk medicine, and the evidence is ample enough to suggest that clinical trials are the next important step to determine the medical role of this natural botanical.
Direct applications in dermatology have not yet been seen, but given the antioxidant and anti-inflammatory activities exhibited by this aporphine alkaloid, there is cause to promote its use in research. Boldine is already being incorporated into several cosmeceutical moisturizers, antiaging sera, eye and lip balms, and antioxidant masks available online.
Boldo (Peumus boldus Mol.) is a slow-growing, shrubby evergreen tree native to the Chilean and Peruvian Andes. It is also found in Morocco and other parts of North Africa, and is cultivated in Europe. The plant has traditionally been used in South American folk medicine, particularly in Chile, Peru, and Brazil, to treat a wide range of conditions of the liver, bowel, and gallbladder (Pharmacol. Res. 1994;29:1–12).
The primary active constituent identified in the tree is boldine, a simple aporphine alkaloid. Several aporphine alkaloids, which are secondary metabolites, are found in boldo leaves, with boldine being the most abundant (Curr. Med. Chem. Anticancer Agents 2005;5:173–82). Boldine is extracted from the leaves and bark of the tree (Phytother. Res. 2000;14:339–43; Pharmazie 2001;56:242–3).
In Germany and other European countries, the boldo plant is used as a medicinal. It is the subject of a German Commission E monograph that details the acceptable uses of the plant as an herbal drug for liver, gallbladder, and gastric conditions (Blumenthal M., et al. [eds.] The Complete German Commission E Monographs: Therapeutic Guide to Herbal Medicines. Austin, Tex.: American Botanical Council and Boston: Integrative Medicine Communications, 1998, pp. 93–4).
Boldine is used worldwide in homeopathic and herbal medicine, and boldine extract is widely acknowledged as a viable herbal remedy in several pharmacopoeias (Chem. Biol. Interact. 2006;159:1–17; Pharmacol. Res. 1994;29:1–12). Indeed, boldine has been demonstrated to possess antioxidant activity in biologic as well as nonbiologic systems, and it has emerged as an ingredient of great interest for its potential in the treatment of free radical-mediated damage or conditions (Pharmacol. Res. 1994;29:1–12).
Antioxidant Actions
Boldine is now considered one of the strongest natural antioxidants (Chem. Biol. Interact. 2006;159:1–17).
In the early 1990s, the traditional use of Peumus boldus extract prompted a team of researchers to validate some of its therapeutic properties. They found that boldine imparted significant protection in vitro against tert-butyl hydroperoxide-induced toxicity in isolated rat hepatocytes, and in vivo against carbon tetrachloride-induced hepatotoxicity in mice. A test in rats with carrageenan-induced edema also revealed significant and dose-dependent anti-inflammatory effects (Planta Med. 1991;57:110–5). The free radical-scavenging and hepatoprotective properties of this natural compound are now considered well established (Phytother. Res. 2000;14:254–60).
A 2001 study demonstrated that boldine imparts chemoprotective activity in murine liver, reducing the metabolic activation of drug-metabolizing enzymes as well as chemical mutagens (Pharmazie 2001;56:242–3).
Alkaloids semisynthesized from boldine have also been shown to inhibit activity against reactive oxygen species and are believed to represent a potential therapy for inflammatory disorders involving production of reactive oxygen species (Chem. Pharm. Bull. [Tokyo] 2004;52:696–9).
In a study in mice, boldine showed significant antioxidant activity, decreasing the oxidation of low-density lipoprotein. It also lessened atherosclerotic lesion formation in LDL receptor-deficient mice that were fed an atherogenic diet. The authors believe that antioxidant capacity, coupled with the traditional tolerance to boldine in humans, renders it a suitable alternative to vitamin E (Atherosclerosis 2004;173:203–10).
More evidence of boldine's antioxidant effects emerged from a study in which it protected intact red blood cells against hemolytic damage caused by the free radical initiator 2,2′-azobis-(2-amidinopropane) (AAPH). The effect was concentration dependent and occurred whether the herb was added simultaneously with, or 1 hour before, AAPH. Erythrocytes previously incubated with AAPH for 2 hours were largely unaffected by the addition of boldine. The investigators concluded that boldine had significant time-dependent cytoprotective as well as antioxidant activity (Phytother. Res. 2000;14:339–43).
It is noteworthy that boldine is found in plants other than the Chilean boldo. In a study of boldine and other aporphine alkaloids isolated from Lindera angustifolia Chen, a Chinese medicinal plant used for edema and rheumatic pain, the extract exhibited significant free radical-scavenging activity against 2,2-diphenyl-1-picrylhydrazyl. It also showed antinociceptive properties, which are thought to be associated with the capacity to scavenge free radicals (J. Ethnopharmacol. 2006;106:408–13).
Other Therapeutic Actions
Boldine has been shown to exert cytoprotective, anti-tumor promoting, anti-inflammatory, antidiabetic, and antiatherogenic activities, all of which may arise from its free radical-scavenging properties. This potent alkaloid also has been shown to confer significant pharmacologic benefit not related to oxidative stress, such as antitrypanocidal, vasorelaxing, immuno- and neuromodulatory, and cholagogic and/or choleretic activity (Chem. Biol. Interact. 2006;159:1–17).
In a study of carrageenan-induced edema in guinea pigs, boldine exhibited dose-dependent anti-inflammatory activity. It also acted against bacterial pyrogen-induced hyperthermia in rabbits. In addition, an in vitro arm of the same study revealed that boldine inhibited prostaglandin biosynthesis, to which investigators attributed the in vivo anti-inflammatory and antipyretic activities of boldine (Agents Actions 1994;42:114–7).
Boldine is contraindicated in people who have kidney disease, women who are pregnant or breast-feeding, and patients with liver bile duct obstruction or severe liver disease (Brinker F. Herb Contraindications and Drug Interactions. Sandy, Ore.: Eclectic Medical Publications, 1997, p. 26).
Photoprotective Action
In a recent study with the most direct dermatologic implications, boldine was shown to be photostable, with its antioxidative capacity remaining intact, thereby allowing the compound to confer photoprotection (J. Photochem. Photobiol. B 2005;80:65–9). Furthermore, in vitro tests of compounds extracted from lichens and the boldo tree revealed that their ultraviolet filtering power was similar to, or better than, that of octylmethoxycinnamate, suggesting their potential usefulness in sunscreen formulations (J. Photochem. Photobiol. B 2002;68:133–9).
Conclusions
Natural antioxidants are too plentiful, and the number under active investigation for medical and cosmetic uses too copious, to suggest that any one compound is the antioxidant du jour. That said, boldine has been studied with increasing frequency over the past 15 years, after a long history of use in folk medicine, and the evidence is ample enough to suggest that clinical trials are the next important step to determine the medical role of this natural botanical.
Direct applications in dermatology have not yet been seen, but given the antioxidant and anti-inflammatory activities exhibited by this aporphine alkaloid, there is cause to promote its use in research. Boldine is already being incorporated into several cosmeceutical moisturizers, antiaging sera, eye and lip balms, and antioxidant masks available online.
Boldo (Peumus boldus Mol.) is a slow-growing, shrubby evergreen tree native to the Chilean and Peruvian Andes. It is also found in Morocco and other parts of North Africa, and is cultivated in Europe. The plant has traditionally been used in South American folk medicine, particularly in Chile, Peru, and Brazil, to treat a wide range of conditions of the liver, bowel, and gallbladder (Pharmacol. Res. 1994;29:1–12).
The primary active constituent identified in the tree is boldine, a simple aporphine alkaloid. Several aporphine alkaloids, which are secondary metabolites, are found in boldo leaves, with boldine being the most abundant (Curr. Med. Chem. Anticancer Agents 2005;5:173–82). Boldine is extracted from the leaves and bark of the tree (Phytother. Res. 2000;14:339–43; Pharmazie 2001;56:242–3).
In Germany and other European countries, the boldo plant is used as a medicinal. It is the subject of a German Commission E monograph that details the acceptable uses of the plant as an herbal drug for liver, gallbladder, and gastric conditions (Blumenthal M., et al. [eds.] The Complete German Commission E Monographs: Therapeutic Guide to Herbal Medicines. Austin, Tex.: American Botanical Council and Boston: Integrative Medicine Communications, 1998, pp. 93–4).
Boldine is used worldwide in homeopathic and herbal medicine, and boldine extract is widely acknowledged as a viable herbal remedy in several pharmacopoeias (Chem. Biol. Interact. 2006;159:1–17; Pharmacol. Res. 1994;29:1–12). Indeed, boldine has been demonstrated to possess antioxidant activity in biologic as well as nonbiologic systems, and it has emerged as an ingredient of great interest for its potential in the treatment of free radical-mediated damage or conditions (Pharmacol. Res. 1994;29:1–12).
Antioxidant Actions
Boldine is now considered one of the strongest natural antioxidants (Chem. Biol. Interact. 2006;159:1–17).
In the early 1990s, the traditional use of Peumus boldus extract prompted a team of researchers to validate some of its therapeutic properties. They found that boldine imparted significant protection in vitro against tert-butyl hydroperoxide-induced toxicity in isolated rat hepatocytes, and in vivo against carbon tetrachloride-induced hepatotoxicity in mice. A test in rats with carrageenan-induced edema also revealed significant and dose-dependent anti-inflammatory effects (Planta Med. 1991;57:110–5). The free radical-scavenging and hepatoprotective properties of this natural compound are now considered well established (Phytother. Res. 2000;14:254–60).
A 2001 study demonstrated that boldine imparts chemoprotective activity in murine liver, reducing the metabolic activation of drug-metabolizing enzymes as well as chemical mutagens (Pharmazie 2001;56:242–3).
Alkaloids semisynthesized from boldine have also been shown to inhibit activity against reactive oxygen species and are believed to represent a potential therapy for inflammatory disorders involving production of reactive oxygen species (Chem. Pharm. Bull. [Tokyo] 2004;52:696–9).
In a study in mice, boldine showed significant antioxidant activity, decreasing the oxidation of low-density lipoprotein. It also lessened atherosclerotic lesion formation in LDL receptor-deficient mice that were fed an atherogenic diet. The authors believe that antioxidant capacity, coupled with the traditional tolerance to boldine in humans, renders it a suitable alternative to vitamin E (Atherosclerosis 2004;173:203–10).
More evidence of boldine's antioxidant effects emerged from a study in which it protected intact red blood cells against hemolytic damage caused by the free radical initiator 2,2′-azobis-(2-amidinopropane) (AAPH). The effect was concentration dependent and occurred whether the herb was added simultaneously with, or 1 hour before, AAPH. Erythrocytes previously incubated with AAPH for 2 hours were largely unaffected by the addition of boldine. The investigators concluded that boldine had significant time-dependent cytoprotective as well as antioxidant activity (Phytother. Res. 2000;14:339–43).
It is noteworthy that boldine is found in plants other than the Chilean boldo. In a study of boldine and other aporphine alkaloids isolated from Lindera angustifolia Chen, a Chinese medicinal plant used for edema and rheumatic pain, the extract exhibited significant free radical-scavenging activity against 2,2-diphenyl-1-picrylhydrazyl. It also showed antinociceptive properties, which are thought to be associated with the capacity to scavenge free radicals (J. Ethnopharmacol. 2006;106:408–13).
Other Therapeutic Actions
Boldine has been shown to exert cytoprotective, anti-tumor promoting, anti-inflammatory, antidiabetic, and antiatherogenic activities, all of which may arise from its free radical-scavenging properties. This potent alkaloid also has been shown to confer significant pharmacologic benefit not related to oxidative stress, such as antitrypanocidal, vasorelaxing, immuno- and neuromodulatory, and cholagogic and/or choleretic activity (Chem. Biol. Interact. 2006;159:1–17).
In a study of carrageenan-induced edema in guinea pigs, boldine exhibited dose-dependent anti-inflammatory activity. It also acted against bacterial pyrogen-induced hyperthermia in rabbits. In addition, an in vitro arm of the same study revealed that boldine inhibited prostaglandin biosynthesis, to which investigators attributed the in vivo anti-inflammatory and antipyretic activities of boldine (Agents Actions 1994;42:114–7).
Boldine is contraindicated in people who have kidney disease, women who are pregnant or breast-feeding, and patients with liver bile duct obstruction or severe liver disease (Brinker F. Herb Contraindications and Drug Interactions. Sandy, Ore.: Eclectic Medical Publications, 1997, p. 26).
Photoprotective Action
In a recent study with the most direct dermatologic implications, boldine was shown to be photostable, with its antioxidative capacity remaining intact, thereby allowing the compound to confer photoprotection (J. Photochem. Photobiol. B 2005;80:65–9). Furthermore, in vitro tests of compounds extracted from lichens and the boldo tree revealed that their ultraviolet filtering power was similar to, or better than, that of octylmethoxycinnamate, suggesting their potential usefulness in sunscreen formulations (J. Photochem. Photobiol. B 2002;68:133–9).
Conclusions
Natural antioxidants are too plentiful, and the number under active investigation for medical and cosmetic uses too copious, to suggest that any one compound is the antioxidant du jour. That said, boldine has been studied with increasing frequency over the past 15 years, after a long history of use in folk medicine, and the evidence is ample enough to suggest that clinical trials are the next important step to determine the medical role of this natural botanical.
Direct applications in dermatology have not yet been seen, but given the antioxidant and anti-inflammatory activities exhibited by this aporphine alkaloid, there is cause to promote its use in research. Boldine is already being incorporated into several cosmeceutical moisturizers, antiaging sera, eye and lip balms, and antioxidant masks available online.
Apigenin
Apigenin (5,7,4′-trihydroxyflavone) is a low-toxic, nonmutagenic plant flavonoid that is widely found in herbs (endive, clove, and German chamomile), fruit (apples, cherries, and grapes), beverages (tea and wine), vegetables (beans, broccoli, celery, leeks, onions, barley, parsley, and tomatoes), and propolis (Skin Pharmacol. Appl. Skin Physiol. 2002;15:297–306; Eur. J. Cancer 1996;32A:146–51; J. Cell Biochem. [Suppl.] 1997;28–9:39–48).
Apigenin shows promising chemopreventive activity against skin cancer (J. Pharm. Sci. 1997;86:721–5) and has demonstrated anti-inflammatory properties (Skin Pharmacol. Appl. Skin Physiol. 2001;14:373–85). It is also believed to be partly responsible for the soothing, antispasmodic, anxiolytic activity that has been attributed to chamomile (Planta Medica 1995;61:213–6).
Antitumor Actions in Animals
In a series of studies conducted almost 2 decades ago, the topical application of apigenin to Sencar mice inhibited, in a dose-dependent manner, skin tumorigenesis initiated by 7,12-dimethylbenz[a]anthracene (DMBA) and promoted by 12-O-tetradecanoylphorbol-13-acetate (TPA). In the first study, 48% of DMBA/TPA-treated mice developed carcinomas by 33 weeks after DMBA initiation, but no carcinomas occurred in the DMBA/apigenin/TPA-treated groups. In the second study, apigenin prolonged the latency period of papilloma formation by 3 weeks and dose dependently reduced papilloma incidence. Apigenin also significantly inhibited carcinoma incidence and reduced the number of tumors. In addition, the researchers concluded that apigenin exhibited the tendency to reduce conversion of papillomas to carcinomas (Cancer Res. 1990;50:499–502).
Several studies conducted since then established that the topical application of apigenin inhibits UV-induced skin tumorigenesis in mouse skin (Mol. Carcinog. 2002;33:36–43; Carcinogenesis 1996;17:2367–75; Mol. Carcinog. 1997;19:74–82). Apigenin also has been shown to suppress TPA-mediated tumor promotion in mouse skin, partly because of its inhibitory effects on protein kinase C and expression of c-Jun and c-Fos (Eur. J. Cancer 1996;32A:146–51).
In addition to its ability to inhibit tumors, apigenin has been noted for its in vitro antioxidant properties against the superoxide anion and peroxyl radicals. In a study performed 15 years ago, the compound demonstrated anti-inflammatory activity in rats. Intradermal application of liposomal apigenin-7-glucoside dose-dependently inhibited skin inflammation previously induced by injection of xanthine oxidase and cumene hydroperoxide (Arzneimittelforschung 1993;43:370–2).
Researchers who studied the effects of apigenin using the mouse keratinocyte 308 cell line, which contains a wild-type p53 gene, determined that the compound may exert antitumorigenic activity by stimulating the p53-p21/waf1 response pathway (Carcinogenesis 2000;21:633–9).
In another study of apigenin's inhibitory influence on skin tumorigenesis, investigators found, using DNA flow cytometric analysis, interruptions in the cell cycle. Keratinocytes cultured for 24 hours in apigenin-containing medium induced a G2/M arrest in two mouse skin-derived cell lines, C50 and 308, and in human HL-60 cells. This effect was fully reversible after an additional 24 hours in apigenin-free medium (Carcinogenesis 1996;17:2367–75).
Subsequent research from the same laboratory provided evidence that apigenin can induce G1 arrest in human diploid fibroblasts by inhibiting cyclin-dependent kinase 2 (cdk2) activity and phosphorylation of retinoblastoma protein, and by inducing the cdk inhibitor p21/waf1.
These activities, the researchers wrote, may mediate the flavonoid's in vivo chemopreventive activities (Mol. Carcinog. 1997;19:74–82).
The preponderance of research on this botanical antioxidant points toward anticarcinogenic activity. In a study evaluating 15 flavonoids for their effects on morphologic changes in soft agar and cellular growth in v-H-ras-transformed NIH3T3 cells, only apigenin, kaempferol, and genistein had a reversing effect on the transformed morphology of these cells. The researchers concluded that the suppression of protein kinase C activity and nuclear oncogene expression might contribute to the molecular mechanism of action exhibited by apigenin (as well as curcumin) in its inhibition of TPA-induced tumor promotion (J. Cell Biochem. [Suppl.] 1997;28–9:39–48).
Other authors have expressed optimistism that apigenin will show a broad spectrum of chemopreventive effects by influencing various molecular targets that affect pathways in the cell (J. Nutr. 2003;133:3800S-4S).
Alternative Sunscreen?
In a study aimed at ascertaining the efficacy of apigenin as a chemopreventive agent against UV-induced skin cancer as well as DNA damage in a cell-free system, investigators found that apigenin treatment from 12 hours before and until 1 hour after UVA/B exposure inhibited 25%–45% of ornithine decarboxylase activity. Further, apigenin treatment of SKH-1 mouse skin before each UVB exposure lowered cancer incidence (52% inhibition) and increased tumor-free survival, compared with control mice (Anticancer Res. 1997;17:85–91).
Of particular interest related to several promising studies is the speculation among some authors that apigenin may represent an alternative sunscreen agent for humans (Mol. Carcinog. 1997;19:74–82; Carcinogenesis 1996;17:2367–75).
For an apigenin formulation to prevent skin cancer, though, it has been determined that the apigenin must be delivered into viable epidermis (Pharm. Res. 1996;13:1710–5). In vivo skin penetration studies of the flavonoids apigenin, luteolin, and apigenin 7-O-?-glucoside demonstrated several years ago that the compounds were adsorbed at the skin surface, but also penetrated into deeper layers (Pharmazie 1994;49:509–11).
Down the Road
The stage may be set for apigenin to be included in formulations, because, in addition to the expanding body of evidence indicating its anticarcinogenic properties, recent work has shown apigenin's potential as an antiphotoaging agent.
Researchers focusing on identifying antiphotoaging compounds assessed the antioxidative activity and inhibitory effects on matrix metalloproteinase-1 (MMP-1) of the extracts of a marine plant, Zostera marina L. These extracts contained apigenin-7-O-β-D-glucoside, chrysoeriol, and luteolin. All of the compounds were found to scavenge the 1,1-diphenyl-2-picrylhydrazyl radical and the superoxide radical. These botanical constituents are deemed to have antioxidative activity and inhibitory effects on MMP-1 expression, and are considered promising targets for inclusion in antiphotoaging formulations (Arch. Pharm. Res. 2004;27:177–83).
Conclusions
The great upsurge in research and interest in plant polyphenols in recent years has been characterized by greater understanding of these compounds' potential health benefits. The body of research on the phenolic flavonoid apigenin is relatively small, with the preponderance of data accumulating in the past 15 years.
Apigenin is found in German chamomile and is most likely to be included in dermatologic products featuring chamomile. It is also an active ingredient in propolis.
With its promising research profile indicating anticarcinogenic and antiphotoaging effects, in vitro and in vivo, much more research regarding this potent antioxidant is likely and warranted.
Apigenin (5,7,4′-trihydroxyflavone) is a low-toxic, nonmutagenic plant flavonoid that is widely found in herbs (endive, clove, and German chamomile), fruit (apples, cherries, and grapes), beverages (tea and wine), vegetables (beans, broccoli, celery, leeks, onions, barley, parsley, and tomatoes), and propolis (Skin Pharmacol. Appl. Skin Physiol. 2002;15:297–306; Eur. J. Cancer 1996;32A:146–51; J. Cell Biochem. [Suppl.] 1997;28–9:39–48).
Apigenin shows promising chemopreventive activity against skin cancer (J. Pharm. Sci. 1997;86:721–5) and has demonstrated anti-inflammatory properties (Skin Pharmacol. Appl. Skin Physiol. 2001;14:373–85). It is also believed to be partly responsible for the soothing, antispasmodic, anxiolytic activity that has been attributed to chamomile (Planta Medica 1995;61:213–6).
Antitumor Actions in Animals
In a series of studies conducted almost 2 decades ago, the topical application of apigenin to Sencar mice inhibited, in a dose-dependent manner, skin tumorigenesis initiated by 7,12-dimethylbenz[a]anthracene (DMBA) and promoted by 12-O-tetradecanoylphorbol-13-acetate (TPA). In the first study, 48% of DMBA/TPA-treated mice developed carcinomas by 33 weeks after DMBA initiation, but no carcinomas occurred in the DMBA/apigenin/TPA-treated groups. In the second study, apigenin prolonged the latency period of papilloma formation by 3 weeks and dose dependently reduced papilloma incidence. Apigenin also significantly inhibited carcinoma incidence and reduced the number of tumors. In addition, the researchers concluded that apigenin exhibited the tendency to reduce conversion of papillomas to carcinomas (Cancer Res. 1990;50:499–502).
Several studies conducted since then established that the topical application of apigenin inhibits UV-induced skin tumorigenesis in mouse skin (Mol. Carcinog. 2002;33:36–43; Carcinogenesis 1996;17:2367–75; Mol. Carcinog. 1997;19:74–82). Apigenin also has been shown to suppress TPA-mediated tumor promotion in mouse skin, partly because of its inhibitory effects on protein kinase C and expression of c-Jun and c-Fos (Eur. J. Cancer 1996;32A:146–51).
In addition to its ability to inhibit tumors, apigenin has been noted for its in vitro antioxidant properties against the superoxide anion and peroxyl radicals. In a study performed 15 years ago, the compound demonstrated anti-inflammatory activity in rats. Intradermal application of liposomal apigenin-7-glucoside dose-dependently inhibited skin inflammation previously induced by injection of xanthine oxidase and cumene hydroperoxide (Arzneimittelforschung 1993;43:370–2).
Researchers who studied the effects of apigenin using the mouse keratinocyte 308 cell line, which contains a wild-type p53 gene, determined that the compound may exert antitumorigenic activity by stimulating the p53-p21/waf1 response pathway (Carcinogenesis 2000;21:633–9).
In another study of apigenin's inhibitory influence on skin tumorigenesis, investigators found, using DNA flow cytometric analysis, interruptions in the cell cycle. Keratinocytes cultured for 24 hours in apigenin-containing medium induced a G2/M arrest in two mouse skin-derived cell lines, C50 and 308, and in human HL-60 cells. This effect was fully reversible after an additional 24 hours in apigenin-free medium (Carcinogenesis 1996;17:2367–75).
Subsequent research from the same laboratory provided evidence that apigenin can induce G1 arrest in human diploid fibroblasts by inhibiting cyclin-dependent kinase 2 (cdk2) activity and phosphorylation of retinoblastoma protein, and by inducing the cdk inhibitor p21/waf1.
These activities, the researchers wrote, may mediate the flavonoid's in vivo chemopreventive activities (Mol. Carcinog. 1997;19:74–82).
The preponderance of research on this botanical antioxidant points toward anticarcinogenic activity. In a study evaluating 15 flavonoids for their effects on morphologic changes in soft agar and cellular growth in v-H-ras-transformed NIH3T3 cells, only apigenin, kaempferol, and genistein had a reversing effect on the transformed morphology of these cells. The researchers concluded that the suppression of protein kinase C activity and nuclear oncogene expression might contribute to the molecular mechanism of action exhibited by apigenin (as well as curcumin) in its inhibition of TPA-induced tumor promotion (J. Cell Biochem. [Suppl.] 1997;28–9:39–48).
Other authors have expressed optimistism that apigenin will show a broad spectrum of chemopreventive effects by influencing various molecular targets that affect pathways in the cell (J. Nutr. 2003;133:3800S-4S).
Alternative Sunscreen?
In a study aimed at ascertaining the efficacy of apigenin as a chemopreventive agent against UV-induced skin cancer as well as DNA damage in a cell-free system, investigators found that apigenin treatment from 12 hours before and until 1 hour after UVA/B exposure inhibited 25%–45% of ornithine decarboxylase activity. Further, apigenin treatment of SKH-1 mouse skin before each UVB exposure lowered cancer incidence (52% inhibition) and increased tumor-free survival, compared with control mice (Anticancer Res. 1997;17:85–91).
Of particular interest related to several promising studies is the speculation among some authors that apigenin may represent an alternative sunscreen agent for humans (Mol. Carcinog. 1997;19:74–82; Carcinogenesis 1996;17:2367–75).
For an apigenin formulation to prevent skin cancer, though, it has been determined that the apigenin must be delivered into viable epidermis (Pharm. Res. 1996;13:1710–5). In vivo skin penetration studies of the flavonoids apigenin, luteolin, and apigenin 7-O-?-glucoside demonstrated several years ago that the compounds were adsorbed at the skin surface, but also penetrated into deeper layers (Pharmazie 1994;49:509–11).
Down the Road
The stage may be set for apigenin to be included in formulations, because, in addition to the expanding body of evidence indicating its anticarcinogenic properties, recent work has shown apigenin's potential as an antiphotoaging agent.
Researchers focusing on identifying antiphotoaging compounds assessed the antioxidative activity and inhibitory effects on matrix metalloproteinase-1 (MMP-1) of the extracts of a marine plant, Zostera marina L. These extracts contained apigenin-7-O-β-D-glucoside, chrysoeriol, and luteolin. All of the compounds were found to scavenge the 1,1-diphenyl-2-picrylhydrazyl radical and the superoxide radical. These botanical constituents are deemed to have antioxidative activity and inhibitory effects on MMP-1 expression, and are considered promising targets for inclusion in antiphotoaging formulations (Arch. Pharm. Res. 2004;27:177–83).
Conclusions
The great upsurge in research and interest in plant polyphenols in recent years has been characterized by greater understanding of these compounds' potential health benefits. The body of research on the phenolic flavonoid apigenin is relatively small, with the preponderance of data accumulating in the past 15 years.
Apigenin is found in German chamomile and is most likely to be included in dermatologic products featuring chamomile. It is also an active ingredient in propolis.
With its promising research profile indicating anticarcinogenic and antiphotoaging effects, in vitro and in vivo, much more research regarding this potent antioxidant is likely and warranted.
Apigenin (5,7,4′-trihydroxyflavone) is a low-toxic, nonmutagenic plant flavonoid that is widely found in herbs (endive, clove, and German chamomile), fruit (apples, cherries, and grapes), beverages (tea and wine), vegetables (beans, broccoli, celery, leeks, onions, barley, parsley, and tomatoes), and propolis (Skin Pharmacol. Appl. Skin Physiol. 2002;15:297–306; Eur. J. Cancer 1996;32A:146–51; J. Cell Biochem. [Suppl.] 1997;28–9:39–48).
Apigenin shows promising chemopreventive activity against skin cancer (J. Pharm. Sci. 1997;86:721–5) and has demonstrated anti-inflammatory properties (Skin Pharmacol. Appl. Skin Physiol. 2001;14:373–85). It is also believed to be partly responsible for the soothing, antispasmodic, anxiolytic activity that has been attributed to chamomile (Planta Medica 1995;61:213–6).
Antitumor Actions in Animals
In a series of studies conducted almost 2 decades ago, the topical application of apigenin to Sencar mice inhibited, in a dose-dependent manner, skin tumorigenesis initiated by 7,12-dimethylbenz[a]anthracene (DMBA) and promoted by 12-O-tetradecanoylphorbol-13-acetate (TPA). In the first study, 48% of DMBA/TPA-treated mice developed carcinomas by 33 weeks after DMBA initiation, but no carcinomas occurred in the DMBA/apigenin/TPA-treated groups. In the second study, apigenin prolonged the latency period of papilloma formation by 3 weeks and dose dependently reduced papilloma incidence. Apigenin also significantly inhibited carcinoma incidence and reduced the number of tumors. In addition, the researchers concluded that apigenin exhibited the tendency to reduce conversion of papillomas to carcinomas (Cancer Res. 1990;50:499–502).
Several studies conducted since then established that the topical application of apigenin inhibits UV-induced skin tumorigenesis in mouse skin (Mol. Carcinog. 2002;33:36–43; Carcinogenesis 1996;17:2367–75; Mol. Carcinog. 1997;19:74–82). Apigenin also has been shown to suppress TPA-mediated tumor promotion in mouse skin, partly because of its inhibitory effects on protein kinase C and expression of c-Jun and c-Fos (Eur. J. Cancer 1996;32A:146–51).
In addition to its ability to inhibit tumors, apigenin has been noted for its in vitro antioxidant properties against the superoxide anion and peroxyl radicals. In a study performed 15 years ago, the compound demonstrated anti-inflammatory activity in rats. Intradermal application of liposomal apigenin-7-glucoside dose-dependently inhibited skin inflammation previously induced by injection of xanthine oxidase and cumene hydroperoxide (Arzneimittelforschung 1993;43:370–2).
Researchers who studied the effects of apigenin using the mouse keratinocyte 308 cell line, which contains a wild-type p53 gene, determined that the compound may exert antitumorigenic activity by stimulating the p53-p21/waf1 response pathway (Carcinogenesis 2000;21:633–9).
In another study of apigenin's inhibitory influence on skin tumorigenesis, investigators found, using DNA flow cytometric analysis, interruptions in the cell cycle. Keratinocytes cultured for 24 hours in apigenin-containing medium induced a G2/M arrest in two mouse skin-derived cell lines, C50 and 308, and in human HL-60 cells. This effect was fully reversible after an additional 24 hours in apigenin-free medium (Carcinogenesis 1996;17:2367–75).
Subsequent research from the same laboratory provided evidence that apigenin can induce G1 arrest in human diploid fibroblasts by inhibiting cyclin-dependent kinase 2 (cdk2) activity and phosphorylation of retinoblastoma protein, and by inducing the cdk inhibitor p21/waf1.
These activities, the researchers wrote, may mediate the flavonoid's in vivo chemopreventive activities (Mol. Carcinog. 1997;19:74–82).
The preponderance of research on this botanical antioxidant points toward anticarcinogenic activity. In a study evaluating 15 flavonoids for their effects on morphologic changes in soft agar and cellular growth in v-H-ras-transformed NIH3T3 cells, only apigenin, kaempferol, and genistein had a reversing effect on the transformed morphology of these cells. The researchers concluded that the suppression of protein kinase C activity and nuclear oncogene expression might contribute to the molecular mechanism of action exhibited by apigenin (as well as curcumin) in its inhibition of TPA-induced tumor promotion (J. Cell Biochem. [Suppl.] 1997;28–9:39–48).
Other authors have expressed optimistism that apigenin will show a broad spectrum of chemopreventive effects by influencing various molecular targets that affect pathways in the cell (J. Nutr. 2003;133:3800S-4S).
Alternative Sunscreen?
In a study aimed at ascertaining the efficacy of apigenin as a chemopreventive agent against UV-induced skin cancer as well as DNA damage in a cell-free system, investigators found that apigenin treatment from 12 hours before and until 1 hour after UVA/B exposure inhibited 25%–45% of ornithine decarboxylase activity. Further, apigenin treatment of SKH-1 mouse skin before each UVB exposure lowered cancer incidence (52% inhibition) and increased tumor-free survival, compared with control mice (Anticancer Res. 1997;17:85–91).
Of particular interest related to several promising studies is the speculation among some authors that apigenin may represent an alternative sunscreen agent for humans (Mol. Carcinog. 1997;19:74–82; Carcinogenesis 1996;17:2367–75).
For an apigenin formulation to prevent skin cancer, though, it has been determined that the apigenin must be delivered into viable epidermis (Pharm. Res. 1996;13:1710–5). In vivo skin penetration studies of the flavonoids apigenin, luteolin, and apigenin 7-O-?-glucoside demonstrated several years ago that the compounds were adsorbed at the skin surface, but also penetrated into deeper layers (Pharmazie 1994;49:509–11).
Down the Road
The stage may be set for apigenin to be included in formulations, because, in addition to the expanding body of evidence indicating its anticarcinogenic properties, recent work has shown apigenin's potential as an antiphotoaging agent.
Researchers focusing on identifying antiphotoaging compounds assessed the antioxidative activity and inhibitory effects on matrix metalloproteinase-1 (MMP-1) of the extracts of a marine plant, Zostera marina L. These extracts contained apigenin-7-O-β-D-glucoside, chrysoeriol, and luteolin. All of the compounds were found to scavenge the 1,1-diphenyl-2-picrylhydrazyl radical and the superoxide radical. These botanical constituents are deemed to have antioxidative activity and inhibitory effects on MMP-1 expression, and are considered promising targets for inclusion in antiphotoaging formulations (Arch. Pharm. Res. 2004;27:177–83).
Conclusions
The great upsurge in research and interest in plant polyphenols in recent years has been characterized by greater understanding of these compounds' potential health benefits. The body of research on the phenolic flavonoid apigenin is relatively small, with the preponderance of data accumulating in the past 15 years.
Apigenin is found in German chamomile and is most likely to be included in dermatologic products featuring chamomile. It is also an active ingredient in propolis.
With its promising research profile indicating anticarcinogenic and antiphotoaging effects, in vitro and in vivo, much more research regarding this potent antioxidant is likely and warranted.
Bromelain (Pineapple Extract)
Bromelain is a designation referring to the family of sulfhydryl-containing proteolytic enzymes derived from the stem of the pineapple plant, Ananas comosus (Altern. Med. Rev. 2003;8:359–77).
Pineapple has been used as a folk medicine in tropical regions such as Hawaii, as well as in Japan and Taiwan, for centuries.
It continues to be used to clean wounds and burns in those regions. As an oral supplement, bromelain is typically administered to aid digestion. It also is considered a natural blood thinner, and has long been part of traditional tropical health regimens for its range of anti-inflammatory properties (Skin Therapy Lett. 2000;5:1–2, 5). Bromelain is considered by some to be as effective as some of the popular NSAIDs.
The most common use of bromelain is for the treatment of inflammation and soft tissue injuries.
Therapeutic Effects
The pharmacologic properties of pineapple's constituent bromelain have been gradually uncovered by Western medicine during the last 4 decades. Bromelain inhibits platelet aggregation, exhibits fibrinolytic activity, has anti-inflammatory action, promotes skin debridement, and interferes with the growth of malignant cells (J. Ethnopharmacol. 1988;22:191–203).
Studies performed 40 years ago showed that the oral administration of bromelain reduced edema, bruising, pain, and healing time after dental surgery. Although postsurgical administration was seen as effective, a combination of pre- and postoperative administration was recommended (J. Dent. Med. 1965;20:51–4; J. Dent. Med. 1964;19:73–7).
Studies performed since the 1960s have confirmed bromelain's beneficial effects after surgery or trauma (Altern. Med. Rev. 2003;8:359–77; Obstet. Gynecol. 1967;29:275–8; Eye Ear Nose Throat Mon. 1968;47:634–9; J. Obstet. Gynaecol. Br. Commonw. 1972;79:951–3; Skin Therapy Lett. 2000;5:1–2, 5; Altern. Med. Rev. 1998;3:302–5).
In a study of patients undergoing rhinoplasty, 53 patients were randomized to one of two bromelain treatment groups or placebo. Edema and ecchymosis lasted for 7 days in the placebo group but only 2 days in both bromelain groups (Eye Ear Nose Throat Mon. 1962;41:813–7). A few years later, a randomized study of 154 facial plastic surgery patients showed no significant differences in edema between bromelain and a placebo (Acta Chir. Scand. 1966;131:193–6).
An uncontrolled trial performed a decade ago suggested that bromelain reduces edema, tenderness, and pain, at rest and in motion, in patients with blunt trauma to the musculoskeletal system (Fortschr. Med. 1995;113:303–6). In a more recent study of a proteolytic enzyme formulation containing bromelain, patients with long bone fractures given the botanical exhibited significantly less postoperative edema than the placebo group (Acta Chir. Orthop. Traumatol. Cech. 2001;68:45–9).
These effects are largely ascribed to the anti-inflammatory capacity of the plant enzyme (Altern. Med. Rev. 2003;8:359–77). In vitro and in vivo studies have shown that the various proteinases contained in bromelain have antiedematous, anti-inflammatory, antithrombotic, and fibrinolytic activities (Cell. Mol. Life Sci. 2001;58:1234–45).
The topical application of a bromelain cream (35% bromelain in a lipid base) has been shown to confer specific benefits, including eliminating burn debris and accelerating wound healing. Escharase, a nonpro-teolytic constituent, is credited with imparting these effects (Altern. Med. Rev. 1998;3:302–5).
Bromelain has been demonstrated to enhance the potentiation of antibiotics (Altern. Med. Rev. 1998;3:302–5), and to confer benefits in the treatment of angina pectoris, bronchitis, sinusitis, thrombophlebitis, pyelonephritis, and wounds (Cell. Mol. Life Sci. 2001;58:1234–45).
In animal experiments, bromelain has been found to inhibit coagulation, primarily by the stimulation of serum fibrinolytic activity, disruption of fibrinogen synthesis, and the related degradation of fibrin and fibrinogen.
Bromelain has also been shown to inhibit experimentally induced tumors in animals, predominantly dose dependently, and exhibit antiedematous and anti-inflammatory activity (Planta Med. 1990;56:249–53).
Recent studies suggest the usefulness of oral bromelain as an immunomodulatory tumor therapy, as it shows a time- and dose-dependent capacity to enhance, in vivo, the immunocytotoxicity of monocytes against tumor cells and to induce production of cytokines, including tumor necrosis factor-α, interleukin-1 β, Il-6, and Il-8 (Cell. Mol. Life Sci. 2001;58:1234–45).
Renewed interest in bromelain, after a drop-off for several years, has resulted in a spate of recent studies and evidence of oral efficacy. Such results, coupled with bromelain's positive safety profile, have brought increasing acceptance of this botanical among consumers and some practitioners (Cell. Mol. Life Sci. 2001;58:1234–45).
The discovery of oral efficacy helped to surmount earlier uncertainty about the bioavailability of bromelain. A study of 19 healthy human males found that small levels of undegraded bromelain traveled intact through the gastrointestinal tract (Am. J. Physiol. 1997;273:G139–46).
While the primary component of bromelain is the sulfhydryl proteolytic fraction, it also contains a peroxidase, acid phosphatase, several protease inhibitors, and organically bound calcium. Bromelain's pharmacologic activities, although often ascribed to the proteolytic fraction, cannot be wholly attributed to that portion as there is evidence that several of its constituents have beneficial properties (Altern. Med. Rev. 1998;3:302–5). Bromelain's mechanism of action has been ascribed partly to its modulation of the arachidonic acid cascade (J. Ethnopharmacol. 1988;22:191–203).
The pineapple enzyme is believed to inhibit the production of proinflammatory prostaglandins, initiate the production of anti-inflammatory series 1 prostaglandins, and reduce capillary permeability (Med. Hypotheses 1980;6:99–104).
A study of a commercial polyenzyme preparation containing bromelain showed that it induced cytokine production in vitro in peripheral blood mononuclear cells. This capacity to induce cytokine production has been cited as a reason for the antitumor effects of such bromelain-containing enzyme formulations (Oncology 1993;50:403–7).
On the Market
Bromelain has been approved by the German Commission E for postsurgical and/or posttraumatic edema, particularly of the nasal and paranasal sinuses characteristic of some plastic surgery. A patented cutaneous tape containing bromelain is also available in Europe for debriding scar tissue.
Although it is no longer commercially available, Ananase, used for healing wounds and resolving certain hematomas, contained bromelain as the main active ingredient and was included in the Physicians' Desk Reference in the early 1960s. Taken orally 1 hour before or 2 hours after meals, bromelain supplements are absorbed by white blood cells and enhance their enzymatic activity (Dermatol. Ther. 2003;16:106–13).
Bromelain has been known to cause allergic reactions such as asthma, rhinitis, and gastrointestinal symptoms (Clin. Allergy 1979;9:443–50). Such occurrences are rare, however.
The botanical is contraindicated in children, people with allergies to pineapple or bee stings, individuals with a history of heart palpitations, and patients taking blood thinners.
In My Practice
We began using bromelain supplements in our patients about a year ago, with spectacular results. We have them take 500 mg twice a day for 3 days after botulinum toxin injections, dermal fillers, surgeries, or other procedures that may result in bruising. We do not have patients take the supplements prior to the procedure because it seems to increase bruising. (Arnica tablets can be used prior to the procedure.)
I have seen bruising resolve much more rapidly when patients take these supplements. One of my patients had a facelift and ate pineapple three times a day, and her lack of bruising was amazing.
I had a basal cell carcinoma removed from my lid margin, which required a 1-cm-by-7-mm excision. I took bromelain supplements (even though the surgeon told me not to), and he was amazed at my lack of bruising. I have not seen any allergic reactions or complications.
I have not had time to do a formal study of this botanical, but I wanted to share my experience with you. Please send me your recommendations for preventing and treating bruising. I plan to do a future column on bruising and its treatment and prevention. Thanks to you all for your continued letters, suggestions, and input. Keep it coming!
Bromelain, a family of sulfhydryl-containing proteolytic enzymes derived from the stems of pineapples, is used to treat inflammation and soft tissue injuries. Donna Franki/Elsevier Global Medical News
Bromelain is a designation referring to the family of sulfhydryl-containing proteolytic enzymes derived from the stem of the pineapple plant, Ananas comosus (Altern. Med. Rev. 2003;8:359–77).
Pineapple has been used as a folk medicine in tropical regions such as Hawaii, as well as in Japan and Taiwan, for centuries.
It continues to be used to clean wounds and burns in those regions. As an oral supplement, bromelain is typically administered to aid digestion. It also is considered a natural blood thinner, and has long been part of traditional tropical health regimens for its range of anti-inflammatory properties (Skin Therapy Lett. 2000;5:1–2, 5). Bromelain is considered by some to be as effective as some of the popular NSAIDs.
The most common use of bromelain is for the treatment of inflammation and soft tissue injuries.
Therapeutic Effects
The pharmacologic properties of pineapple's constituent bromelain have been gradually uncovered by Western medicine during the last 4 decades. Bromelain inhibits platelet aggregation, exhibits fibrinolytic activity, has anti-inflammatory action, promotes skin debridement, and interferes with the growth of malignant cells (J. Ethnopharmacol. 1988;22:191–203).
Studies performed 40 years ago showed that the oral administration of bromelain reduced edema, bruising, pain, and healing time after dental surgery. Although postsurgical administration was seen as effective, a combination of pre- and postoperative administration was recommended (J. Dent. Med. 1965;20:51–4; J. Dent. Med. 1964;19:73–7).
Studies performed since the 1960s have confirmed bromelain's beneficial effects after surgery or trauma (Altern. Med. Rev. 2003;8:359–77; Obstet. Gynecol. 1967;29:275–8; Eye Ear Nose Throat Mon. 1968;47:634–9; J. Obstet. Gynaecol. Br. Commonw. 1972;79:951–3; Skin Therapy Lett. 2000;5:1–2, 5; Altern. Med. Rev. 1998;3:302–5).
In a study of patients undergoing rhinoplasty, 53 patients were randomized to one of two bromelain treatment groups or placebo. Edema and ecchymosis lasted for 7 days in the placebo group but only 2 days in both bromelain groups (Eye Ear Nose Throat Mon. 1962;41:813–7). A few years later, a randomized study of 154 facial plastic surgery patients showed no significant differences in edema between bromelain and a placebo (Acta Chir. Scand. 1966;131:193–6).
An uncontrolled trial performed a decade ago suggested that bromelain reduces edema, tenderness, and pain, at rest and in motion, in patients with blunt trauma to the musculoskeletal system (Fortschr. Med. 1995;113:303–6). In a more recent study of a proteolytic enzyme formulation containing bromelain, patients with long bone fractures given the botanical exhibited significantly less postoperative edema than the placebo group (Acta Chir. Orthop. Traumatol. Cech. 2001;68:45–9).
These effects are largely ascribed to the anti-inflammatory capacity of the plant enzyme (Altern. Med. Rev. 2003;8:359–77). In vitro and in vivo studies have shown that the various proteinases contained in bromelain have antiedematous, anti-inflammatory, antithrombotic, and fibrinolytic activities (Cell. Mol. Life Sci. 2001;58:1234–45).
The topical application of a bromelain cream (35% bromelain in a lipid base) has been shown to confer specific benefits, including eliminating burn debris and accelerating wound healing. Escharase, a nonpro-teolytic constituent, is credited with imparting these effects (Altern. Med. Rev. 1998;3:302–5).
Bromelain has been demonstrated to enhance the potentiation of antibiotics (Altern. Med. Rev. 1998;3:302–5), and to confer benefits in the treatment of angina pectoris, bronchitis, sinusitis, thrombophlebitis, pyelonephritis, and wounds (Cell. Mol. Life Sci. 2001;58:1234–45).
In animal experiments, bromelain has been found to inhibit coagulation, primarily by the stimulation of serum fibrinolytic activity, disruption of fibrinogen synthesis, and the related degradation of fibrin and fibrinogen.
Bromelain has also been shown to inhibit experimentally induced tumors in animals, predominantly dose dependently, and exhibit antiedematous and anti-inflammatory activity (Planta Med. 1990;56:249–53).
Recent studies suggest the usefulness of oral bromelain as an immunomodulatory tumor therapy, as it shows a time- and dose-dependent capacity to enhance, in vivo, the immunocytotoxicity of monocytes against tumor cells and to induce production of cytokines, including tumor necrosis factor-α, interleukin-1 β, Il-6, and Il-8 (Cell. Mol. Life Sci. 2001;58:1234–45).
Renewed interest in bromelain, after a drop-off for several years, has resulted in a spate of recent studies and evidence of oral efficacy. Such results, coupled with bromelain's positive safety profile, have brought increasing acceptance of this botanical among consumers and some practitioners (Cell. Mol. Life Sci. 2001;58:1234–45).
The discovery of oral efficacy helped to surmount earlier uncertainty about the bioavailability of bromelain. A study of 19 healthy human males found that small levels of undegraded bromelain traveled intact through the gastrointestinal tract (Am. J. Physiol. 1997;273:G139–46).
While the primary component of bromelain is the sulfhydryl proteolytic fraction, it also contains a peroxidase, acid phosphatase, several protease inhibitors, and organically bound calcium. Bromelain's pharmacologic activities, although often ascribed to the proteolytic fraction, cannot be wholly attributed to that portion as there is evidence that several of its constituents have beneficial properties (Altern. Med. Rev. 1998;3:302–5). Bromelain's mechanism of action has been ascribed partly to its modulation of the arachidonic acid cascade (J. Ethnopharmacol. 1988;22:191–203).
The pineapple enzyme is believed to inhibit the production of proinflammatory prostaglandins, initiate the production of anti-inflammatory series 1 prostaglandins, and reduce capillary permeability (Med. Hypotheses 1980;6:99–104).
A study of a commercial polyenzyme preparation containing bromelain showed that it induced cytokine production in vitro in peripheral blood mononuclear cells. This capacity to induce cytokine production has been cited as a reason for the antitumor effects of such bromelain-containing enzyme formulations (Oncology 1993;50:403–7).
On the Market
Bromelain has been approved by the German Commission E for postsurgical and/or posttraumatic edema, particularly of the nasal and paranasal sinuses characteristic of some plastic surgery. A patented cutaneous tape containing bromelain is also available in Europe for debriding scar tissue.
Although it is no longer commercially available, Ananase, used for healing wounds and resolving certain hematomas, contained bromelain as the main active ingredient and was included in the Physicians' Desk Reference in the early 1960s. Taken orally 1 hour before or 2 hours after meals, bromelain supplements are absorbed by white blood cells and enhance their enzymatic activity (Dermatol. Ther. 2003;16:106–13).
Bromelain has been known to cause allergic reactions such as asthma, rhinitis, and gastrointestinal symptoms (Clin. Allergy 1979;9:443–50). Such occurrences are rare, however.
The botanical is contraindicated in children, people with allergies to pineapple or bee stings, individuals with a history of heart palpitations, and patients taking blood thinners.
In My Practice
We began using bromelain supplements in our patients about a year ago, with spectacular results. We have them take 500 mg twice a day for 3 days after botulinum toxin injections, dermal fillers, surgeries, or other procedures that may result in bruising. We do not have patients take the supplements prior to the procedure because it seems to increase bruising. (Arnica tablets can be used prior to the procedure.)
I have seen bruising resolve much more rapidly when patients take these supplements. One of my patients had a facelift and ate pineapple three times a day, and her lack of bruising was amazing.
I had a basal cell carcinoma removed from my lid margin, which required a 1-cm-by-7-mm excision. I took bromelain supplements (even though the surgeon told me not to), and he was amazed at my lack of bruising. I have not seen any allergic reactions or complications.
I have not had time to do a formal study of this botanical, but I wanted to share my experience with you. Please send me your recommendations for preventing and treating bruising. I plan to do a future column on bruising and its treatment and prevention. Thanks to you all for your continued letters, suggestions, and input. Keep it coming!
Bromelain, a family of sulfhydryl-containing proteolytic enzymes derived from the stems of pineapples, is used to treat inflammation and soft tissue injuries. Donna Franki/Elsevier Global Medical News
Bromelain is a designation referring to the family of sulfhydryl-containing proteolytic enzymes derived from the stem of the pineapple plant, Ananas comosus (Altern. Med. Rev. 2003;8:359–77).
Pineapple has been used as a folk medicine in tropical regions such as Hawaii, as well as in Japan and Taiwan, for centuries.
It continues to be used to clean wounds and burns in those regions. As an oral supplement, bromelain is typically administered to aid digestion. It also is considered a natural blood thinner, and has long been part of traditional tropical health regimens for its range of anti-inflammatory properties (Skin Therapy Lett. 2000;5:1–2, 5). Bromelain is considered by some to be as effective as some of the popular NSAIDs.
The most common use of bromelain is for the treatment of inflammation and soft tissue injuries.
Therapeutic Effects
The pharmacologic properties of pineapple's constituent bromelain have been gradually uncovered by Western medicine during the last 4 decades. Bromelain inhibits platelet aggregation, exhibits fibrinolytic activity, has anti-inflammatory action, promotes skin debridement, and interferes with the growth of malignant cells (J. Ethnopharmacol. 1988;22:191–203).
Studies performed 40 years ago showed that the oral administration of bromelain reduced edema, bruising, pain, and healing time after dental surgery. Although postsurgical administration was seen as effective, a combination of pre- and postoperative administration was recommended (J. Dent. Med. 1965;20:51–4; J. Dent. Med. 1964;19:73–7).
Studies performed since the 1960s have confirmed bromelain's beneficial effects after surgery or trauma (Altern. Med. Rev. 2003;8:359–77; Obstet. Gynecol. 1967;29:275–8; Eye Ear Nose Throat Mon. 1968;47:634–9; J. Obstet. Gynaecol. Br. Commonw. 1972;79:951–3; Skin Therapy Lett. 2000;5:1–2, 5; Altern. Med. Rev. 1998;3:302–5).
In a study of patients undergoing rhinoplasty, 53 patients were randomized to one of two bromelain treatment groups or placebo. Edema and ecchymosis lasted for 7 days in the placebo group but only 2 days in both bromelain groups (Eye Ear Nose Throat Mon. 1962;41:813–7). A few years later, a randomized study of 154 facial plastic surgery patients showed no significant differences in edema between bromelain and a placebo (Acta Chir. Scand. 1966;131:193–6).
An uncontrolled trial performed a decade ago suggested that bromelain reduces edema, tenderness, and pain, at rest and in motion, in patients with blunt trauma to the musculoskeletal system (Fortschr. Med. 1995;113:303–6). In a more recent study of a proteolytic enzyme formulation containing bromelain, patients with long bone fractures given the botanical exhibited significantly less postoperative edema than the placebo group (Acta Chir. Orthop. Traumatol. Cech. 2001;68:45–9).
These effects are largely ascribed to the anti-inflammatory capacity of the plant enzyme (Altern. Med. Rev. 2003;8:359–77). In vitro and in vivo studies have shown that the various proteinases contained in bromelain have antiedematous, anti-inflammatory, antithrombotic, and fibrinolytic activities (Cell. Mol. Life Sci. 2001;58:1234–45).
The topical application of a bromelain cream (35% bromelain in a lipid base) has been shown to confer specific benefits, including eliminating burn debris and accelerating wound healing. Escharase, a nonpro-teolytic constituent, is credited with imparting these effects (Altern. Med. Rev. 1998;3:302–5).
Bromelain has been demonstrated to enhance the potentiation of antibiotics (Altern. Med. Rev. 1998;3:302–5), and to confer benefits in the treatment of angina pectoris, bronchitis, sinusitis, thrombophlebitis, pyelonephritis, and wounds (Cell. Mol. Life Sci. 2001;58:1234–45).
In animal experiments, bromelain has been found to inhibit coagulation, primarily by the stimulation of serum fibrinolytic activity, disruption of fibrinogen synthesis, and the related degradation of fibrin and fibrinogen.
Bromelain has also been shown to inhibit experimentally induced tumors in animals, predominantly dose dependently, and exhibit antiedematous and anti-inflammatory activity (Planta Med. 1990;56:249–53).
Recent studies suggest the usefulness of oral bromelain as an immunomodulatory tumor therapy, as it shows a time- and dose-dependent capacity to enhance, in vivo, the immunocytotoxicity of monocytes against tumor cells and to induce production of cytokines, including tumor necrosis factor-α, interleukin-1 β, Il-6, and Il-8 (Cell. Mol. Life Sci. 2001;58:1234–45).
Renewed interest in bromelain, after a drop-off for several years, has resulted in a spate of recent studies and evidence of oral efficacy. Such results, coupled with bromelain's positive safety profile, have brought increasing acceptance of this botanical among consumers and some practitioners (Cell. Mol. Life Sci. 2001;58:1234–45).
The discovery of oral efficacy helped to surmount earlier uncertainty about the bioavailability of bromelain. A study of 19 healthy human males found that small levels of undegraded bromelain traveled intact through the gastrointestinal tract (Am. J. Physiol. 1997;273:G139–46).
While the primary component of bromelain is the sulfhydryl proteolytic fraction, it also contains a peroxidase, acid phosphatase, several protease inhibitors, and organically bound calcium. Bromelain's pharmacologic activities, although often ascribed to the proteolytic fraction, cannot be wholly attributed to that portion as there is evidence that several of its constituents have beneficial properties (Altern. Med. Rev. 1998;3:302–5). Bromelain's mechanism of action has been ascribed partly to its modulation of the arachidonic acid cascade (J. Ethnopharmacol. 1988;22:191–203).
The pineapple enzyme is believed to inhibit the production of proinflammatory prostaglandins, initiate the production of anti-inflammatory series 1 prostaglandins, and reduce capillary permeability (Med. Hypotheses 1980;6:99–104).
A study of a commercial polyenzyme preparation containing bromelain showed that it induced cytokine production in vitro in peripheral blood mononuclear cells. This capacity to induce cytokine production has been cited as a reason for the antitumor effects of such bromelain-containing enzyme formulations (Oncology 1993;50:403–7).
On the Market
Bromelain has been approved by the German Commission E for postsurgical and/or posttraumatic edema, particularly of the nasal and paranasal sinuses characteristic of some plastic surgery. A patented cutaneous tape containing bromelain is also available in Europe for debriding scar tissue.
Although it is no longer commercially available, Ananase, used for healing wounds and resolving certain hematomas, contained bromelain as the main active ingredient and was included in the Physicians' Desk Reference in the early 1960s. Taken orally 1 hour before or 2 hours after meals, bromelain supplements are absorbed by white blood cells and enhance their enzymatic activity (Dermatol. Ther. 2003;16:106–13).
Bromelain has been known to cause allergic reactions such as asthma, rhinitis, and gastrointestinal symptoms (Clin. Allergy 1979;9:443–50). Such occurrences are rare, however.
The botanical is contraindicated in children, people with allergies to pineapple or bee stings, individuals with a history of heart palpitations, and patients taking blood thinners.
In My Practice
We began using bromelain supplements in our patients about a year ago, with spectacular results. We have them take 500 mg twice a day for 3 days after botulinum toxin injections, dermal fillers, surgeries, or other procedures that may result in bruising. We do not have patients take the supplements prior to the procedure because it seems to increase bruising. (Arnica tablets can be used prior to the procedure.)
I have seen bruising resolve much more rapidly when patients take these supplements. One of my patients had a facelift and ate pineapple three times a day, and her lack of bruising was amazing.
I had a basal cell carcinoma removed from my lid margin, which required a 1-cm-by-7-mm excision. I took bromelain supplements (even though the surgeon told me not to), and he was amazed at my lack of bruising. I have not seen any allergic reactions or complications.
I have not had time to do a formal study of this botanical, but I wanted to share my experience with you. Please send me your recommendations for preventing and treating bruising. I plan to do a future column on bruising and its treatment and prevention. Thanks to you all for your continued letters, suggestions, and input. Keep it coming!
Bromelain, a family of sulfhydryl-containing proteolytic enzymes derived from the stems of pineapples, is used to treat inflammation and soft tissue injuries. Donna Franki/Elsevier Global Medical News