Isoflavones: Red Clover, Genistein, and Daidzein
Recently, red clover, whose isoflavones had previously been shown to contribute to a low incidence of osteoporosis and menopausal symptoms in high dietary concentrations, was examined for anti-aging effects. Investigators orally administered red clover extract containing 11% isoflavones to ovariectomized rats for 14 weeks, and found that collagen levels increased significantly in the treatment group as compared to the control group. Epidermal thickness and keratinization were normal in the treated group, but were reduced in the control group. The authors concluded that the regular dietary consumption of red clover isoflavones can alleviate cutaneous aging brought on by declines in estrogen (Phytother. Res. 2006;20:1096-9).
In a recent study evaluating the feasibility of skin absorption of the soy isoflavones genistein, daidzein, and glycitein, both genistein and daidzein inhibited UVB-induced hydrogen peroxide synthesis in keratinocytes. Analysis of vehicle effects on in vitro topical delivery revealed that genistein showed better skin absorption than daidzein. The investigators concluded that the topical application of soy isoflavones shows promise as a treatment for photoaging and photodamage (Int. J. Pharm. 2008;364:36-44).
Indeed, the topical application of isoflavones, including genistein and daidzein, has been shown to protect pig skin from photodamage caused by solar-simulated ultraviolet irradiation. Notably, the isoflavone compounds tested were less effective than a topical antioxidant formulation containing vitamins C and E and the phenolic acid ferulic acid (Photodermatol. Photoimmunol. Photomed. 2008;24:61-6).
Catechins (Flavanols): Epigallocatechin 3-gallate
Already considered a potent antioxidant, EGCG continues to receive attention for conferring an expanding range of health benefits. This compound, the most abundant and potent catechin in green tea, has been shown to hinder UVB-induced collagen-degrading matrix metalloproteinases (Food Chem. Toxicol. 2008;46:1298-307).
A different study of EGCG indicated that it hampered the proliferation and migration of keloid fibroblasts in vitro, and also curbed in vivo signs of keloids, by interrupting the signal transducer and activator of the transcription-3 signaling pathway. As a result of these findings, the investigators proposed EGCG as a preventive and therapeutic agent for keloids (J. Invest. Dermatol. 2008;128:2429-41). EGCG also has been suggested as a potential therapeutic approach to atopic dermatitis, given its success against AD-like skin lesions in a murine model (Int. Immunopharmacol. 2008;8:1172-82).
Anthocyanins: Cyanidin
Clearly, all flavonoids are not equal. In a recent study, methanol extracts of black raspberries, strawberries, and blueberries were tested for their capacity to inhibit UV-induced activation of nuclear transcription factor-kappa B (NF-kappaB) and activator protein-1 (AP-1) in mouse epidermal cells. The methanol fractions of black raspberries, which contain the anthocyanin cyanidin 3-rutinoside, were found to time- and dose-dependently inhibit the effects of UV on NF-kappaB and AP-1, unlike the other berries, which do not contain cyanidin 3-rutinoside (Nutr. Cancer 2007;58:205-12).
Another form of cyanidin has also been shown to impart cutaneous benefits. Specifically, pretreatment of human keratinocytes with the anthocyanin cyanidin 3-O-glucoside has been demonstrated to protect against a wide array of UVB-induced damage (J. Agric. Food Chem. 2006;54:4041-7).
Proanthocyanidins: Pycnogenol
Investigators studied pycnogenol in an antioxidant mixture that also included evening primrose and vitamins C and E. After 10 weeks of oral administration to female SKH-1 hairless mice exposed to UVB irradiation three times weekly, the mixture was found to significantly inhibit wrinkle formation by suppressing UVB-induced matrix metalloproteinase activity while promoting collagen production (Photodermatol. Photoimmunol. Photomed. 2007;23:155-62).
Tannins: Ellagic Acid
In a double-blind, placebo-controlled, 4-week trial, investigators assessed the effects of orally administered ellagic acid-rich pomegranate extract on the pigmentation of 13 women after UV exposure. Healthy volunteers were randomly assigned to high-dose, low-dose, and control groups. The results showed that luminance values decreased by 1.73% in the high-dose group and 1.35% in the low-dose group, compared with the control group, and stains and freckles also were diminished (J. Nutr. Sci. Vitaminol. (Tokyo) 2006;52:383-8).
Stilbenes: Resveratrol
The antioxidant potency of resveratrol has been cited for conferring a wide range of salutary effects, including antitumorigenic and antiaging activity. Recently, a resveratrol-based skin care formulation intended to combat photoaging was reported to exhibit 17-fold greater antioxidant activity than idebenone (J. Cosmet. Dermatol. 2008;7:2-7). In a different study, resveratrol, the primary active polyphenolic constituent in red wine, was assessed in terms of topical/transdermal delivery viability, given the previously established benefits shown via systemic administration. Several hydrogel systems used as resveratrol vehicles were shown to be safe and effective methods for cutaneously delivering the therapeutic effects of this antioxidant (Biol. Pharm. Bull. 2008;31:955-62).
Phenolic Acids: Ferulic Acid
In a small study, a stable formulation of 15% L-corbic acid, 1% alpha-tocopherol, and 0.5% ferulic acid was applied topically to normal-appearing human skin for 4 days, and was found to confer significant photoprotection against solar-simulated UV radiation. The preparation was especially effective at diminishing thymine dimer mutations, which are linked to skin cancer. The authors also noted that the mechanism of action of this antioxidant formulation differs from that of sunscreens and, therefore, may serve as a supplement to such products (J. Am. Acad. Dermatol. 2008;59:418-25). It is worth noting that ferulic acid has been approved as a sunscreen agent in Japan (J. Pharm. Biomed. Anal. 2008;46:645-52).