Dual mechanistic role of polyphenols in modulating the insulin-related metabolic pathways: insights from computer-aided analysis

The intricate computer-aided analysis has been employed to investigate the different aspects of insulin cooperation with polyphenols, including quercetin, resveratrol, sesamin, gallic and salicylic acids. Molecular docking and molecular dynamics simulations revealed that quercetin, resveratrol and sesamin binding to the insulin via hotspot amino acid residues Phe24-Tyr26 results in opening of protein structure and stabilization of Phe24, the steps which are critical for initiating the insulin binding to its receptor. Network pharmacology analysis coupled with bioactivity and toxicity predictions underscored the potential of quercetin, resveratrol and gallic acid to interact with pivotal insulin metabolic pathways, namely, AMPK and mTOR. The revealed capability of quercetin and resveratrol to alter directly the structure of insulin coupled with their ability to modify protein metabolic pathways, underscores the dual positive mechanistic influence these polyphenols have in the management of insulin-centric impairments.