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

Oriental Pharmacy and Experimental Medicine 2020년 20권 3호 p.427 ~ 438
Khanal Pukar, Patil B. M.,
소속 상세정보
 ( Khanal Pukar ) - KLE College of Pharmacy Department of Pharmacology and Toxicology
 ( Patil B. M. ) - KLE College of Pharmacy Department of Pharmacology and Toxicology

Abstract


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.

키워드

α-Glucosidase; Docking; Duranta erecta; Flavonoids; Scutellarein

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