Activation of the erythrocyte plasma membrane redox system by resveratrol: a possible mechanism for antioxidant properties Syed Ibrahim Rizvi, Kanti Bhooshan Pandey Correspondence: Abstract: Resveratrol is one of the most widely studied of all the plant-produced polyphenols and has diverse, beneficial health effects includ- ing anti-cancer and cardio-protective effects. Many of the biological actions of this polyphenol have been attributed to its antioxidant properties. Erythrocytes contain a plasma membrane redox system (PMRS), which transfers electrons from intracellular donors (NADH and/or ascorbate (ASC)) to extracellular acceptors. There is evidence that the intracellular ASC donates electrons to extra- cellular ascorbate free radicals (AFRs) via the PMRS, which encompasses an AFR reductase; such a redox system enables the cells to effectively counteract oxidative processes. We present evidence to show that human erythrocytes take up resveratrol, and once in- side the cell, resveratrol can donate electrons to extracellular electron acceptors through the erythrocyte PMRS and AFR reductase. Incubating human erythrocytes with resveratrol (10 μM) caused a significant activation of the PMRS (41%) and AFR reductase (30%) over (basal level) the control; the effect of resveratrol was concentration-dependent. The electron donating ability of resvera- trol is slightly less than that observed with quercetin. The role of resveratrol in activating the erythrocyte PMRS and AFR reductase may assume significance in all disease conditions in which there is a decrease in plasma antioxidant potential. Key words: erythrocyte, resveratrol, PMRS, AFR reductase, antioxidant Introduction Resveratrol is a natural phytoalexin polyphenolic compound found largely in the skin of grapes and is well known for its presence in red wine [16]. Its stilbene-based structure has two phenolic rings linked by a styrene double bond, which allows the cis and trans orientations to generate 3,4’,5-trihydroxystil- bene (Fig. 1). Growing evidence suggests that res- veratrol may play an important role in prevention of human diseases such as cancer, cardiovascular dis- ease, diabetes and aging [32]. Many of the biological actions of this polyphenol have been attributed to its antioxidant properties [18, 22]. Studies show that human erythrocytes contain a plasma membrane redox system (PMRS), which transfers electrons from intracellular donors (NADH and/or ascorbate (ASC)) to extracellular acceptors, al- though the physiological acceptor is still unclear [20]. There is evidence that the intracellular ASC donates electrons to extracellular ascorbate free radicals (AFRs) via the PMRS, which encompasses an AFR reductase; such a redox system enables the cells to ef- 726