Aesthetic Dermatology

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).

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