Pedunculagin is an ellagitannin, a group of polyphenolic hydrolyzable tannins, found in various plants, including Emblica officinalis, Pimenta dioica, and several others ( Arch. Pharm. Res. 2014, Feb 7. [Epub ahead of print] ; Curr. Drug Targets 2012;13:1900-06). The substance is reported to exhibit anti-inflammatory, anticancer, and antimicrobial activities, and it is considered a potent dietary antioxidant ( Z. Naturforsch C. 2007;62:526-36 ; J. Org. Chem. 1996;61:2606-12 ; J. Nutr. 2014;144(4 Suppl):555S-60S ). Purified from the Manchurian alder (Alnus hirsuta), pedunculagin is also a novel immunomodulating agent ( Skin Res. Technol. 2010;16:371-7 ). Pedunculagin is also one of the hydrolyzable tannins found in Punica granatum (pomegranate), fruit extracts of which have been shown by Afaq et al. to exert photochemopreventive effects against the deleterious effects of ultraviolet B radiation ( Photochem. Photobiol. 2005;81:38-45 ). Pedunculagin was first synthesized (in 2,3- and 4,6-coupled form) in 1996 ( J. Org. Chem. 1996;61:2606-12 ).

Anticancer and antioxidant activity

In a study of 57 tannins and related compounds, Kashiwada et al. noted in a 1992 study that pedunculagin exhibited selective cytotoxicity against melanoma cells ( J. Nat. Prod. 1992;55:1033-43 ).

According to a 2007 report by Marzouk et al., pedunculagin is among one of several tannins identified in the leaves of Pimenta dioica, and it is among the most potent free radical scavengers, as well as one of the most cytotoxic substances against solid tumor cancer cells. Pedunculagin also was found to significantly suppress nitric oxide production and spur the proliferation of T-lymphocytes and macrophages ( Z. Naturforsch C. 2007;62:526-36 ).

In 2012, Kähkönen et al. observed that red raspberry and cloudberry ellagitannins, including pedunculagin, acted as effective radical scavengers, substantially contributing to the antioxidant activity of the berries in lipoprotein and lipid emulsion environments ( J. Agric. Food Chem. 2012;60:1167-74 ).

A 2014 review by Hardman summarized several studies suggesting that potent anticancer properties, including antiproliferative and antiangiogenic activities, have been linked to walnuts. She noted that pedunculagin is one of the key constituents in walnuts to which such characteristics have been attributed ( J. Nutr. 2014;144(4 Suppl):555S-60S ).

Potential cutaneous applications

In 2010, Lee et al. assessed the effects of pedunculagin on 2,4,6-trinitrochlorobenzene (TNCB)-induced atopic dermatitis-like lesions in NC/Nga mice. Investigators applied a cream containing 0.1% or 0.5% pedunculagin to the positive treatment group; the negative treatment group received the base cream without pedunculagin, with no topical formulations administered to a control group. The investigators found, 4 weeks after treatment, that greater and more rapid improvement in the lesions was experienced by the group that received the higher concentration of pedunculagin ( Skin Res. Technol. 2010;16:371-7 ).

Kim et al., in 2014, isolated pedunculagin and five other phenolic compounds from the leaves of Quercus mongolica (Mongolian oak). They found that pedunculagin exhibited strong in vitro inhibition against the expression of matrix metalloproteinase (MMP)-1 and increased type I procollagen in human fibroblasts exposed to UVB. The Q. mongolica constituent was also found to concentration-dependently exhibit potent scavenging activity against the DPPH (2,2-diphenyl-1-picrylhydrazyl) radical. The investigators suggested that the ellagitannin shows promise for use in preventing and treating cutaneous aging ( Arch. Pharm. Res. 2014 Feb. 7. [Epub ahead of print] ).

Conclusion

Pedunculagin shows some promise as an agent that can yield dermatologic benefits. However, the body of research on this natural compound is relatively scant. More expansive follow-up work is needed to determine the extent to which pedunculagin can be reasonably incorporated into the dermatologic armamentarium.

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

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