Resveratrol was reported in 8,000 publications and 7,332 biological studies so far. Most cases reported an activity in the range of 1-50 mMol for the inhibition of enzymes and protein-protein interaction. What is the underlying principle for this extremely promiscuous activity? As a 3,5-diphenol, resveratrol is less prone to be oxidized to quinoid structures. Quinones may derive from curcumin, which is teratogenic in zebrafish larvae at 2 uMol/L, or EGCG, which was classified as weakly embryotoxic.

Thus, there seems to be a good reason for the very low oral bioavailability of most polyphenols: their brain permeation is close to zero. The Seliwanov reaction of carbohydrates and polyphenols occurs readily at 37°C in 0.1 N HCl; this will impair the oral availability of such dirty compounds already upon digestion both in rats or humans. The pharmaceutical industry is very reluctant to pursue polyphenolic lead structures. The investigation of cleaner compounds may get us to the relevant issues faster.

References:
Wang CC, Chu KO, Chong WS, Li WY, Pang CP, Shum AS, Lau TK, Rogers MS. Tea epigallocatechin-3-gallate increases 8-isoprostane level and induces caudal regression in developing rat embryos. Free Radic Biol Med. 2007 Aug 15;43(4):519-27. Abstract

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