A Study on the Effects of Inhibition Mechanism of Curcumin, Quercetin, and Resveratrol on Human Glutathione Reductase Through and Approaches

Glutathione reductase (GR) is a major antioxidant enzyme essential to maintain GSH/GSSG ratio by catalyzing recovery of reduced glutathione (GSH) from oxidized glutathione (GSSG). Because of this vital task, the inhibition of GR is an important target in the treatment of many diseases, so we aimed to identify natural and new GR inhibitors to be guide for drug design.For this purpose, two different approaches were used. The first one is inhibition, the first phase of which was the purification of the enzyme from human erythrocyte by 2', 5'-ADP Sepharose 4B affinity chromatography, and then the inhibition effects of curcumin, quercetin, and resveratrol were examined. The second one is study, which was performed to elucidate the drug-likeness, active site identification and inhibition mechanisms of these compounds.hGR was isolated from human erythrocytes with 7.036 EU/mg protein specific activity and 48.97% yield. Then, IC values were as 17.25 ± 3.8 µM, 57.8 ± 14.2 µM, and 520 ± 96.7 µM for curcumin, quercetin, and resveratrol respectively. Docking studies of compounds were performed against hGR receptors with induced-fit docking method. The compound showed Glide score as 10.519 kcal/mol, -9.789, and -8.133 respectively.In conclusion, it was seen that curcumin is the much better inhibitor than quercetin and resveratrol for hGR according to both and studies. Curcumin, a potential inhibitor of hGR, can be used in drug design to target the glutathione system in cellular injury.Communicated by Ramaswamy H. Sarma.