Review of plant phenolics, part 3: Nonflavonoid compounds

Polyphenols are widely distributed in the plant kingdom, and are found in copious supply in multiple vegetables, fruits, herbs, grains, tea, coffee beans, honey, and red wine, for example. They are an especially important source of antioxidants and are increasingly the focus of research due to their potent and diverse biologic activities. In the conclusion to my three-part review of polyphenols, this column identifies representative compounds from the classes of nonflavonoid polyphenols and provides a brief update on research.

Dr. Leslie S. Baumann

Phenolic acids: ferulic acid

Derived from curcumin, ferulic acid is noted for exhibiting multiple biologic activities, including antiapoptotic, anticarcinogenic, antidiabetic, hepatoprotective, and cardioprotective, among others. Its beneficial effects are thought to be mediated through its antioxidant and anti-inflammatory characteristics.¹ In a small 2008 study, a stable formulation of 15% l-ascorbic acid, 1% alpha-tocopherol, and 0.5% ferulic acid was applied topically to normal-appearing human skin for 4 days and was found to impart significant photoprotection against solar-simulated UV radiation and 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.² (It is worth noting that ferulic acid has been approved as a sunscreen agent in Japan.³)

In 2015, Ambothi et al. used Swiss albino mice to assess the photochemopreventive effects of ferulic acid against chronic (30-week) UVB, finding the intraperitoneal and topical administration of the phenolic acid effective in significantly lowering the incidence of UVB-induced tumor volume and weight in the mice skin.⁴ The next year, Hahn et al. reported that pretreatment with ferulic acid protects human dermal fibroblasts from UVA-induced photodamage.⁵ Also in 2016, Chaiprasongsuk et al. found that several dietary phenolics, including ferulic acid, deliver protection against UVA-induced melanogenesis through indirect regulation of the Nrf2-ARE pathway.⁶

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Lignans: flaxseed

Flaxseed lignans, which exhibit a wide range of biologic activities, are best known for their antioxidant properties.⁷ In a 2017 study using atopic dermatitis–induced NC/Nga mice, Yang et al. found that fermented flaxseed oil administered orally was successful in relieving symptoms such as erythema, edema, pruritus, and epithelial damage.⁸ Two years earlier, Draganescu et al. developed a topical flaxseed extract formulation that displayed wound healing capabilities on Wistar rats.⁷ Emulsions produced from the oils and seeds of transgenic flax have also been found to protect against oxidative stress in hamster fibroblasts, with investigators suggesting that the emulsions have potential to protect the skin against such damage.⁸

Stilbenes: resveratrol

The antioxidant potency of resveratrol has been cited for conferring a wide range of salutary effects, including antitumorigenic as well as antiaging activity. In 2008, a resveratrol-based skin care formulation intended to combat photoaging was reported to exhibit 17-fold greater antioxidant activity than idebenone.⁹ In a different study that year, resveratrol, the primary active polyphenolic constituent in red wine, was assessed in terms of topical/transdermal delivery viability, given 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.¹⁰ Since then, resveratrol has been demonstrated to penetrate the skin via topical administration, reinforcing the antioxidant system of the stratum corneum and delivering increases of antioxidants to human epidermal tissue.¹¹

In 2014, Farris et al. showed that a proprietary topical antioxidant blend of resveratrol, baicalin, and vitamin E applied topically at night yielded statistically significant amelioration of fine lines and wrinkles, as well as skin firmness, elasticity, laxity, hyperpigmentation, radiance, and roughness over a 12-week period.¹² Resveratrol has also been shown in mice to suppress the inflammatory response and improve survival from severe burns with bacterial infections.¹³

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Hydrolyzable tannins: ellagic acid

Ellagic acid, a dimer of gallic acid, has been reported to impart anti-inflammatory, antitumor, immunomodulatory, and antifungal activities.^14-16 Ortiz-Ruiz et al. have noted that while ellagic acid is used as a whitening agent, it can act as a substrate to rather than an inhibitor of tyrosinase, as it is oxidized by the enzyme to an unstable o-quinone. However, as a potent antioxidant, ellagic acid can block melanogenesis by reducing o-quinones and semiquinones.¹⁷

In a double-blind, placebo-controlled, 4-week trial to assess the effects of orally administered ellagic acid–rich pomegranate extract on the pigmentation of 13 women after UV exposure, with healthy volunteers randomly assigned to high-dose, low-dose, and control groups, luminance values decreased by 1.73% in the high-dose group and 1.35% in the low-dose group, as compared with the control group, and stains and freckles were reported to be diminished.¹⁸ A 2016 study in human dermal fibroblasts by Baek et al. suggested that ellagic acid displays antiphotoaging activity, as the polyphenol protected against UVB-induced oxidative stress potentially through an Nrf2-dependent pathway.¹⁵