The perceptions of natural compounds against dipeptidyl peptidase 4 in diabetes: from in silico to in vivo

Dipeptidyl peptidase IV (DPP-4), an incretin glucagon-like peptide-1 (GLP-1) degrading enzyme, contains two forms and it can exert various physiological functions particular in controlling blood glucose through the action of GLP-1. In diabetic use, the DPP-4 inhibitor can block the DDP-4 to attenuate GLP-1 degradation and prolong GLP-1 its action and sensitize insulin activity for the purpose of lowering blood glucose. Nonetheless the adverse effects of DPP-4 inhibitors severely hinder their clinical applications, and notably there is a clinical demand for novel DPP-4 inhibitors from various sources including chemical synthesis, herbs, and plants with fewer side effects. In this review, we highlight various strategies, namely computational biology (in silico), in vitro enzymatic and cell assays, and in vivo animal tests, for seeking natural DPP-4 inhibitors from botanic sources including herbs and plants. The pros and cons of all approaches for new inhibitor candidates or hits will be under discussion.