α-Glucosidase inhibitors from Duranta repens modulate p53 signaling pathway in diabetes mellitus

• DOI: 10.1007/s13596-020-00426-w
• Publication Date: 2020-02-03T15:20:14Z
• Authors: Pukar Khanal; B. M. Patil
• Keywords: Acarbose; Docking (animal); Repens

Hydroalcoholic extract/fraction(s) and scutellarein, a previously reported phytoconstituent from Duranta repens were evaluated for their α-glucosidase inhibitory activity using in vitro method. The reported phytoconstituents were also screened as α-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 α-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 α-glucosidase inhibitory activity and the mode of inhibition was uncompetitive. The predicted α-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 α-glucosidase enzyme. In conclusion, present study identified the fraction rich in flavonoids to possess highest α-glucosidase inhibitory activity and could modulate p53 signaling pathway in diabetic pathogenesis.