Commentary

Polyphenols Everywhere

Many products that tout antioxidant activity include antioxidant ingredients that contain polyphenols.


 

Many products that tout antioxidant activity include antioxidant ingredients that contain polyphenols. There are numerous classes of polyphenols, which are the largest group of phytochemicals and the most broadly disseminated among plants (J. Am. Diet. Assoc. 1999;99:213-8). They are secondary plant metabolites represented by more than 8,000 naturally occurring compounds.

These widely divergent substances, which exhibit various levels of antioxidant activity, share a common structural component: a phenol or an aromatic ring, usually two, with at least one hydroxyl group, that are linked via a three-carbon bond to form a six-unit heterocyclic ring (J. Nutr. 2003;133:3248S-54S).

Attention has been increasingly focused on polyphenols, as they are known to be an important part of, and the most abundant source of antioxidants in, the human diet. They are present in many vegetables, fruits, herbs, grains, teas, and beans, as well as coffee, propolis, and red wine (Biomed. Pap. Med. Fac. Univ. Palacky Olomouc. Czech Repub. 2003;147:137-45; J. Nutr. 2000;130:2073S-85S; Annu. Rev. Nutr. 2002;22:19-34; Pharmacol. Ther. 2001;90:157-77; Free Radic. Biol. Med. 2001;30:1213-22).

The most prevalent and frequently studied polyphenols are known as flavonoids. Based on the connection of an aromatic ring to the heterocyclic ring, as well as the oxidation state and functional groups of the heterocyclic ring, flavonoids are further divided into flavones (based on the 2-phenylchromen-4-one skeleton, e.g., apigenin and luteolin); flavonols (based on the 3-hydroxy-2-phenylchromen-4-one skeleton and functional group, e.g., quercetin, kaempferol, myricetin, and fisetin); flavanones (based on the 2,3-dihydro-2-phenylchromen-4-one skeleton and functional group, e.g., naringenin, hesperetin, and eriodictyol); isoflavones (based on the 3-phenylchromen-4-one skeleton, e.g., genistein and daidzein); flavanols or catechins (based on the 2-phenyl-3,4-dihydro-2H-chromen-3-ol skeleton and functional groups, e.g., epicatechin, epicatechin 3-gallate, epigallocatechin, epigallocatechin 3-gallate (EGCG), catechin, gallocatechin); anthocyanins (based on the 2-phenylchromenylium ion skeleton, e.g., cyanidin and pelargonidin); and proanthocyanidins or condensed tannins (which are polymer chains of flavanols, such as catechins, and include pycnogenol, leukocyanidin, and leucoanthocyanidin) (Annu. Rev. Nutr. 2002;22:19-34; Asia Pac. J. Clin. Nutr. 2004;13:S72; J. Nutr. 2000;130:2073S-85S; J. Nutr. 2003;133:3248S-54S).
Tannins, phenolic polymers of high molecular weight, are divided into three classes: hydrolyzable tannins (e.g., ellagic acid, found in pomegranates, raspberries, strawberries, cranberries, and walnuts), derived tannins (created during food handling and processing and present in black and oolong teas), and condensed tannins, described above (J. Am. Diet. Assoc. 1999;99:213-8; J. Nutr. 2003;133:3248S-54S).

Some specific flavonoids can be found in the following food sources: flavonols in apples with skin, broccoli, olives, onions, and green and black tea; flavones in celery and parsley; flavonones in grapefruit, oranges, and their juices; and catechins (flavanols) in apples with or without skin, dark chocolate, cocoa, red wine, and green and black tea (Asia Pac. J. Clin. Nutr. 2004;13:S72).

There are a plethora of other polyphenols, many of which confer health benefits, including stilbenes (e.g., resveratrol, found in red wine), lignans (e.g., enterodiol, found in flaxseed and flaxseed oil), and phenolic acids, such as hydroxybenzoic and hydroxycinnamic acids, among which caffeic and ferulic acids are often present in foods.

Broad health benefits have been associated with hundreds of polyphenolic substances. Notably, some of the best known research results on polyphenols have reported on the success of various topical applications of green tea catechins, ferulic acid, resveratrol, and other related compounds (many of which have been addressed in this column). The rest of this discussion focuses on new information regarding systemic efficacy, topical delivery, or applications of a representative from several subclasses of these compounds.

Flavonols: Quercetin
A water-in-oil microemulsion containing quercetin has been shown, in porcine skin in vitro and hairless mouse skin in vivo, to enhance the penetration of the flavonol into the stratum corneum, epidermis, and dermis. The preparation also was found to significantly inhibit ultraviolet B (UVB)-induced metalloproteinase activity and glutathione reduction (Eur. J. Pharm. Biopharm. 2008;69:948-57).

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 (Cancer Res. 2008:68:3057-65). In a different study, the apigenin glycosides 7-O-glucuronide, 7-O-methylglucuronide, and pectolinarin also have been demonstrated to induce collagen type I synthesis in fibroblasts. The investigators found that all tested compounds promoted the activity of prolidase, which initiates the last stage of collagen degradation and is integral to collagen production (Int. J. Mol. Med. 2007;20:889-95).

Flavonones: Naringenin
The citrus flavonone naringenin shows promise as a preventive agent against cutaneous aging as well as carcinogenesis. Naringenin has been demonstrated to exert an antiapoptotic effect in UVB-damaged cells, significantly extending long-term cellular survival, and to facilitate the removal of cyclobutane pyrimidine dimers from the genome (Photochem. Photobiol. 2008;84:307-16).

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