Unexpected Role of pH and Microenvironment on the Antioxidant and Synergistic Activity of Resveratrol in Model Micellar and Liposomal Systems

Experimental and theoretical studies indicate that resveratrol (RSV, dietary polyphenol that effectively reduces cellular oxidative stress) is a good scavenger of hydroxyl, alkoxyl, and peroxyl radicals in homogeneous systems. However, the role of RSV as a chain-breaking antioxidant is still questioned. Here, we describe pH dependent effectiveness of RSV as an inhibitor of peroxidation of methyl linoleate in Triton X-100 micelles and in 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) liposomes, with the best effectiveness at pH 6 (stoichiometric factors, n, are 4.9 and 5.6, and the rate constants for reaction with peroxyl radicals, kinh, are 1200 and 3300 M-1 s(-1) in micellar and liposomal systems, respectively). We propose the mechanism in which RSV-derived radicals are coupled to dimers with recovered ability to trap lipidperoxyl radicals. The formation of such dimers is facilitated due to increased local concentration of RSV at the lipid-water interface. Good synergy of RSV with alpha-tocopherol analogue in micelles and liposomes is in contrast to the previously reported lack of synergy in non-polar solvents; however, the increased persistency of tocopheroxyl radicals in dispersed lipid/water systems and proximal localization of both antioxidants greatly facilitate the possible recovery of alpha-TOH by RSV.

Automated summary

Experimental and theoretical studies demonstrate that resveratrol is a potent scavenger of radicals in homogeneous systems. The effectiveness of resveratrol as an inhibitor of lipid peroxidation depends on pH, with the best effectiveness at pH 6. Resveratrol forms dimers with recovered ability to trap lipid peroxyl radicals, facilitated by its increased concentration at the lipid-water interface.