Exploration of phytochemical compounds from Millets as NRF2 activators using molecular docking and molecular dynamics simulation approaches

Abstract

Oxidative stress plays vital role in progression of several diseases like cardiovascular, neurological and gastrointestinal disorders. Millets, on regular consumption, are known to have beneficial effects. They are also rich in phytochemicals. In the current study, these phytochemicals are aimed against the complex of KEAP1-NRF2 and activating NRF-2 which is a potent inducer of anti-oxidant enzymes like heme-oxygenase and superoxide dismutase. Molecular docking was conducted to study compounds that can form an interaction similar to 1VX (co-crystalized ligand). CDOCKER interaction energies of isovitexin, vitexin, kaempferol, protocatechuic acid, and vanillic acid were better than 1VX. The best three molecules- isovitexin, vitexin and kaempferol, based ontheir CDOCKER interaction energy, were subjected to molecular dynamic simulation for 100 ns which revealed their stability at active site. Further MM-PBSA binding free energy of phytochemicals was calculated. Values of isovitexin, vitexin, kaempferol and 1VX are -32.04 Kcal/mol, -24.81Kcal/mol. -4.17 Kcal/mol, and -10.25 Kcal/mol, respectively, which indicate high degree of binding compared to cocrystallized ligand 1VX. Results indicated that selected compounds- isovitexin, vitexin, kaempferol can act as NRF2 activators which further can be confirmed through in vitro and in vivo studies.