Delineating antidiabetic proficiency of catechin from withania somnifera and its inhibitory action on dipeptidyl peptidase-4 (Dpp-4).

Abstract

Dipeptidyl peptidase-4 (DPP-4) is a transmembrane serine aminopeptidase which cleaves X-proline dipeptides which degrades incretin hormones in turn stimulating insulin release with reduced GLP-1 secretion in type 2 diabetes. In this study, maximum inhibitory activity of DPP-4 was established with 100% methanol extract of Withania somnifera (WS) roots and the phytobioactives were further characterized. The active compound responsible for the inhibition of DPP-4 was found to be catechin, which was confirmed by phytobioanalytical studies. STC-1 cells exhibited increased GLP-1 concentration which was evident by dosimetry. The active compound responsible for the inhibition of DPP-4 was found to be catechin which was evident from fluorescence spectroscopy. While CD spectra indicated that catechin binds with the α-helix of the enzyme, resulting in structural and conformational changes in secondary structure at 208 and 222 nm. Further, docking studies exhibited binding affinity of catechin with DPP-4 and was found to be-6.601 kcal/mol as compared to standard potent blockers, further the interaction of catechin with other biotargets confirmed its antidiabetic potency. The current study supports synthetic-pharmacological knowledge for innovation in discovery engine for newer medicines implicating the validation DPP-4 as potent drug target for type 2 diabetes mellitus.