This column picks up with a recent literature review suggesting potential benefits of topically applied or orally administered flavonoid polyphenolic substances. The discussion is based on at least one sample compound from each flavonoid category.

Flavonols: quercetin

Known to exert substantial antioxidant and anti-inflammatory activities, quercetin has been shown in various cellular and animal-based models to deliver photoprotection from UV and contribute to wound healing.1 In a single center, single-blind trial with 30 healthy volunteers, a 1% topical quercetin cream was found to be effective in reducing erythema, itching, and wheal diameter in experimentally-induced skin stress.2 Quercetin also has been reported to have the capacity to inhibit melanin production.3

Flavones: apigenin

The topical application of 4’,5,7-trihydroxyflavone (apigenin) on mouse skin has been shown to decrease skin tumor size and incidence induced by UVB exposure.4 A 2013 series of in vitro (HaCaT skin keratinocytes) and in vivo mice model investigations revealed that topical apigenin lowered the number of cyclobutane pyrimidine dimers, indicating that the flavonoid can protect against UVB-induced reactive oxygen species and DNA damage.5 A different study in mice demonstrated that topically applied apigenin reduced acute irritant contact dermatitis as well as allergic contact dermatitis, significantly decreasing transepidermal water loss and skin surface pH while increasing stratum corneum hydration.6

Flavanones: naringenin

The citrus flavanone naringenin shows promise as a preventive agent against cutaneous aging as well as carcinogenesis. In a 2008 study, naringenin exerted an anti-apoptotic effect in UVB-damaged cells, significantly extending long-term cellular survival, and facilitating the removal of cyclobutane pyrimidine dimers from the genome.7 More recently, topical naringenin has been shown in mice to mitigate the cutaneous inflammation and oxidative stress caused by UVB irradiation,8 and, present in Lippia graveolens, to protect against chronic UVB-induced damage including phototumorigenesis.9

Isoflavones: red clover, genistein, and daidzein

Red clover, the isoflavones of which have been demonstrated – in high dietary concentrations – to contribute to low incidence of osteoporosis and menopausal symptoms, was shown in a 2006 study to exert anti-aging effects in mice, indicating potential for alleviating the cutaneous aging brought on by declines in estrogen.10 In 2011, Lipovac et al. showed that oral supplementation with red clover extract improved scalp hair and skin status as well as libido, mood, sleep, and fatigue in a study with 109 postmenopausal women.11

The topical application of the soy isoflavones genistein, daidzein, and glycitein has shown promise as a treatment for photoaging and photodamage.12 Genistein has been noted for its antioxidant and antibrowning activity, and has exhibited anti-aging properties in mouse studies and photoprotective activity in humans.13 A 2015 study by Zhao et al. in cultured skin fibroblasts and nude mouse skin indicated that daidzein treatment appears to increase skin collagen production and suppress collagen degradation.14

Flavan-3-ols (catechins): epigallocatechin 3-gallate

Already considered a potent antioxidant, epigallocatechin 3-gallate (EGCG) continues to receive attention for conferring an expanding range of health benefits. This catechin, which is the most abundant and potent of such compounds in green tea, has exhibited the capacity to hinder UVB-induced collagen-degrading matrix metalloproteinases (MMPs).15 EGCG also has been proposed as a preventive and therapeutic agent for keloids, given findings indicating that it hampered the proliferation and migration of keloid fibroblasts in vitro, as well as in vivo by interrupting the signal transducer and activator of transcription 3 (STAT3) signaling pathway.16 Further, EGCG has been suggested as a potential therapeutic approach to atopic dermatitis (AD) given success against AD-like skin lesions in a murine model.17 An investigation of the anti-aging cutaneous effects of EGCG on d-galactose-induced aging in mice revealed that subcutaneously injected EGCG yielded overall improvement in the structure and function of the skin.18 EGCG also is known to yield improvements in skin condition by providing DNA protection, reactivating damaged cells, and increasing cellular energy production.3

Perhaps most importantly, formulations containing green tea extracts have been shown in a small study of 20 volunteers to exert protection against photoaging and photoimmunosuppression, with the extract hindering the expression of MMP-9 and MMP-2.19 Wrinkle reduction also was observed in another clinical study involving topical green tea.20 The tea plant Camellia sinensis is one of the best sources of antioxidant catechins, particularly green tea (unfermented), but also white (unfermented), black (fermented), and oolong (semifermented) tea.21

Anthocyanins: cyanidin

A 2017 in vivo study in mice found that cyanidin hindered the binding of the cytokine interleukin-17A to the IL-17RA subunit to reduce inflammation.22 In a 2007 study, methanol extracts of black raspberries, strawberries, and blueberries were tested for the capacity to inhibit UV-induced activation of nuclear 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 UV effects on NF-kappaB and AP-1, unlike the other berries, which do not contain cyanidin-3-rutinoside.23 The pretreatment of human keratinocytes with the anthocyanin cyanidin-3-O-glucoside also has been demonstrated to protect against a wide array of UVB-induced damage,24 and acai fruit–derived cyanidin and malvidin have been shown recently to thwart UVA-induced stress in immortalized fibroblasts.25 Further, cyanidin derived from elderberries has exhibited antiproliferative and apoptotic potential on melanoma cells in a 2017 mouse model, indicating a potential role in skin cancer treatment.26


Divided into six subclasses, flavonoids are the most abundant, diverse, and best studied group of polyphenols. These substances display wide-ranging antioxidant, anti-inflammatory, anti-aging, and antimicrobial effects, and they continue to stake a broader claim as staple ingredients in the topical dermatologic armamentarium.

Dr. Baumann is a private practice dermatologist, researcher, author and entrepreneur who practices in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann wrote two textbooks: “Cosmetic Dermatology: Principles and Practice” (New York: McGraw-Hill, 2002), and “Cosmeceuticals and Cosmetic Ingredients,” (New York: McGraw-Hill, 2014), and a New York Times Best Sellers book for consumers, “The Skin Type Solution” (New York: Bantam Dell, 2006). Dr. Baumann has received funding for advisory boards and/or clinical research trials from Allergan, Evolus, Galderma, and Revance. She is the founder and CEO of Skin Type Solutions Franchise Systems LLC.


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