a-Glucosidase inhibitors from Duranta repensmodulate p53 signaling pathway in diabetes mellitus

Hydroalcoholic extract/fraction(s) and scutellarein, a previously reported phytoconstituent from Duranta repenswere evaluated for their a-glucosidase inhibitory activity using in vitro method. The reported phytoconstituents were also screened as a-glucosidase inhibitor, probable cytotoxicity, ADMET profile, and side effects via in silico models. Further, probable gene expression profile and pathways involved in diabetes/diabetes complications were also screened. Similarly, network was constructed among a-glucosidase inhibitors, modulated proteins and respective pathways and docking study was performed using autodock4.0. Fraction rich in flavonoids was found to possess the highest a-glucosidase inhibitory activity and the mode of inhibition was uncompetitive. The predicted a-glucosidase inhibitors were less cytotoxic to normal cells with lower side effects compared to acarbose. Similarly, gene-set enrichment analysis identified p53 signaling pathway to be primarily modulated by majority of phytoconstituents. Further, docking study revealed scutellarein to have highest binding affinity with a-glucosidase enzyme. In conclusion, present study identified the fraction rich in flavonoids to possess highest a-glucosidase inhibitory activity and could modulate p53 signaling pathway in diabetic pathogenesis.