Modulation of dipeptidyl peptidase IV by Rooibos tea metabolites towards type 2 diabetes care: Evidence from molecular dynamics simulation and density functional theory

Abstract

Despite the reported antidiabetic potential of Rooibos tea, there is still paucity of information on its mechanisms of action to date. This study investigated the antidiabetic potential of Rooibos tea using computational approaches focusing on dipeptidyl peptidase (DPP-IV) implicated in insulin production. Profiling of the 37 secondary metabolites in the tea against DPP-IV and subsequent thermodynamic energy refinement of the lead compounds over a 120-ns simulation, revealed two of the metabolites [esculin (-33.97 kcal/mol) and nothofagin (-44.03 kcal/mol)] as putative leads relative to the reference standard, sitagliptin (-30.7704 kcal/mol). Further structural analysis of the resulting complexes suggests that the two compounds not only formed stable complexes with DPP-IV but also interacted with the binding domain residues imperative to modulation of the enzyme. Taken together, the data from this study are implicative of the structural mechanism of inhibitory action of the putative leads against DPP-IV resulting in hormonal actions that enhances insulin production. While the study has lent credence to the role of the profiled metabolites as drug candidates against DPP-IV in the management of Type 2 diabetes mellitus (T2DM), complementary in vitro as well as preclinical and clinical studies are suggested to fully harness and establish the therapeutic significance of the metabolites in diabetes care.