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Influence of Glucuronidation and Reduction Modifications of Resveratrol on its Biological Activities
Author(s) -
Lu DongLiang,
Ding DeJun,
Yan WenJing,
Li RanRan,
Dai Fang,
Wang Qi,
Yu ShaSha,
Li Yan,
Jin XiaoLing,
Zhou Bo
Publication year - 2013
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.201300080
Subject(s) - chemistry , biological activity , antioxidant , glucuronidation , polyphenol , dpph , resveratrol , biochemistry , in vivo , hemolysis , in vitro , microsome , biology , microbiology and biotechnology , immunology
Resveratrol (3,5,4′‐trihydroxystilbene, RES), a star among dietary polyphenols, shows a wide range of biological activities, but it is rapidly and extensively metabolized into its glucuronide and sulfate conjugates as well as to the corresponding reduced products. This begs the question of whether the metabolites of RES contribute to its in vivo biological activity. To explore this possibility, we synthesized its glucuronidation (3‐GR and 4′‐GR) and reduction (DHR) metabolites, and evaluated the effect of these structure modifications on biological activities, including binding ability with human serum albumin (HSA), antioxidant activity in homogeneous solutions and heterogeneous media, anti‐inflammatory activity, and cytotoxicity against various cancer cell lines. We found that 1) 4′‐GR, DHR and RES show nearly equal binding to HSA, mainly through hydrogen bonding, whereas 3‐GR adopts a quite different orientation mode upon binding, thereby resulting in reduced ability; 2) 3‐GR shows comparable (even equal) ability to RES in FRAP‐ and AAPH‐induced DNA strand breakage assays; DHR, 3‐GR, and 4′‐GR exhibit anti‐hemolysis activity comparable to that of RES; additionally, 3‐GR and DHR retain some degree activity of the parent molecule in DPPH . ‐scavenging and cupric ion‐initiated oxidation of LDL assays, respectively; 3) compared to RES, 4′‐GR displays equipotent ability in the inhibition of COX‐2, and DHR presents comparable activity in inhibiting NO production and growth of SMMC‐7721 cells. Relative to RES, its glucuronidation and reduction metabolites showed equal, comparable, or some degree of activity in the above assays, depending on the specific compound and test model, which probably supports their roles in contributing to the in vivo biological activities of the parent molecule.