Structure-Activity Relationship and Mechanism of the Tocopherol-Regenerating Activity of Resveratrol and Its Analogues

The present study investigated the mechanism of the synergistic antioxidant activity of cc-tocopherol with resveratrol (3,5,4'-trihydroxy-trans-stilbene, 3,5,4'-THS) and its synthetic analogues, that is, 3,4-dihydroxy-trans-stilbene (3,4-DHS), 4,4'-dihydroxy-trans-stilbene (4,4'-DHS), 4-hydroxy-trans-stilbene (4-HS), and 3,5-dihydroxy-trans-stilbene (3,5-DHS). The reaction kinetics of alpha-tocopheroxyl radical with resveratrol and its analogues were studied in sodium dodecyl sulfate (SDS) and cetyl trimethylammonium bromide (CTAB) micelles using the stopped-flow electron paramagnetic resonance (EPR) technique. It was found that resveratrol and its analogues could regenerate alpha-tocopherol with rate constants (k(REG)) in the order of 3,4-DHS > 4,4'-DHS > resveratrol >= 4-HS >= 3,5-DHS in SDS and CTAB micelles. It was found that the analogues bearing o-dihydroxyl groups (3,4-DHS) and p-dihydroxyl groups (4,4'-HS) exhibited remarkably higher alpha-tocopherol-regenerating activity than those bearing no such groups (resveratrol, 4-HS, and 3,5-DHS). In addition, the alpha-tocopherol-regenerating activity of resveratrol and its analogues was correlated with their electrochemical behaviors, suggesting that electron transfer might play a critical role during the regeneration reaction.