In silico molecular docking analysis of major plant flavanols and proteins associated with glucose homeostasis

Diabetes mellitus remains to be a significant global metabolic disorder, affecting both human and animal populations. Plant-derived medications have gained focus for diabetes management due to their perceived safety compared to conventional drugs. Recent research has emphasized the potential of polyphenols, particularly flavonols, in modulating genes related to insulin secretion and signalings pathways, indicating their potential role in preventing type II diabetes. This study investigates the interactions of three plant flavonols—quercetin, kaempferol, and myricetin—with two critical proteins involved in glucose homeostasis: PPAR-γ and GLUT-4 through in-silico docking analysis performed using Biovia Discovery Studio (version 2020). Our docking results revealed that kaempferol showed significant binding affinity for PPAR-γ, with a LibDock score of 95.462, interacting notably with residues THR269 and ASP271. Quercetin demonstrated moderate binding affinity (LibDock score of 46.657), while myricetin exhibited no interactions with PPAR-γ. For GLUT-4, myricetin had the highest docking score of 98.347, indicating strong binding affinity, with favorable interactions at residues SER412, LEU410, SER480, and LYS266. Quercetin also interacted with GLUT-4 (LibDock score: 95.317), binding to residues SER412, LYS266, and LEU410. Kaempferol with a dock score of 92.997 interacted with HIS484 and LYS266. The common interaction of amino acid residue LYS266 with all flavonols underscores its role in mediating their effects. The findings thus highlight the potential of flavonols in influencing glucose homeostasis through interactions with key proteins. Further pharmacokinetic studies and in vitro and in vivo validations are necessary to establish their efficacy and safety as anti-diabetic agents.