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

Adrian Konopko,Grzegorz Litwinienko

doi:10.1021/acs.joc.1c01801

Abstract

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 α-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 α-TOH by RSV.

Highlights

Even the best reducing agent localized outside the biomembranes or micellar lipid phase cannot break the propagation chain, the partition coefficients listed in Table 1 allow us to predict that PMHC and RSV should effectively trap peroxyl radicals within the dispersed lipid phase in contrast to the limited activity of 3,5-DHA and 4-HBA in the lipid phase
The first ones are monolayer aggregates of surfactant that enable the studies of reactions proceeding at the water/lipid interface, whereas Large Unilamellar Vesicles (LUVs) liposomes structurally resemble bilayers
The observed effects cannot be explained by a direct reaction of deprotonated RSV with lipidperoxyl radicals

Summary

Introduction

Among thousands of phytochemicals exhibiting antioxidant activity in vitro and in vivo, great attention has been paid to polyphenols. During the last 20 years, resveratrol (3,4′,5trihydroxy-trans-stilbene, RSV) has gained particular interest because this molecule efficiently protects against environmental stress and pathogenic attack in plants and in mammal organisms. The growing interest started from the 1990s, when a cardioprotective effect of consumption of RSV present in red grapes and red wine was discovered, but RSV can be found in many other plant species. A number of in vitro and in vivo studies proved that RSV exhibits therapeutic potential. Health benefits include cardioprotective and antiinflammation effects, prevention against Alzheimer’s disease and several liver diseases, and decrease of blood glucose level and plasma lipids in mice with a diabetic disorder. there are a number of reports on the anticancer activity of RSV6 against several types of cancers: leukemia, hepatocellular, or prostate carcinoma. Cardioprotective effects of RSV are connected with reduction of oxidative stress due to indirect antioxidant action (RSV upregulates expression of glutathione peroxidase, catalase, and heme oxygenase-1) and due to a direct decomposition of H2O2.8 Intensive clinical and biochemical research was followed by a number of studies of the direct antiradical and antioxidant activity of RSV.

Methods

Results

Conclusion