Plant-Derived DPP-4 Inhibitors in Cardiometabolic Diseases: A Critical Evaluation of the Evidence Base and Priorities for Kazakhstan

Abstract

The increasing prevalence of obesity, type 2 diabetes mellitus, and associated cardiometabolic complications has intensified the challenge of effectively controlling disturbances in carbohydrate metabolism and highlighted the need for new therapeutic targets and approaches. One promising target is the enzyme DPP-4, which inactivates the incretin hormones GLP-1 and GIP, thereby limiting their effects on insulin secretion and postprandial glycemic regulation. In this context, natural compounds are considered a promising source of new chemical scaffolds for the development of DPP-4 inhibitors. The aim of this review is to critically evaluate experimental evidence on plant-derived DPP-4 inhibitors and to identify promising plant sources and chemical scaffolds relevant to Kazakhstan. The analysis considered the chemical class of compounds, DPP-4 inhibitory activity, enzyme source, quantitative activity parameters, available data on kinetics and selectivity, and the potential availability of plant material in Kazakhstan. The most extensive evidence has been reported for flavonoids, chalcones, aurones, and other polyphenolic compounds. Alkaloids containing a berberine structural moiety are also of interest because of their inhibitory activity and the availability of mechanistic explanations. However, their activity is predominantly in the micromolar range and is lower than that of synthetic DPP-4 inhibitors. The evidence base remains heterogeneous because of differences among experimental systems and limited data on kinetics and selectivity. For Kazakhstan, the priority should not be the direct translation of plant-derived compounds into clinical practice, but rather the systematic investigation of promising locally available plant sources using standardized methods.