biostudies-literatureUnknown20(5)Kalhotra PDipeptidyl peptidase-4 (DPP-4) is a well-known therapeutic drug target proven to reduce blood glucose levels in diabetes mellitus, and clinically, DPP-4 inhibitors are used in combination with other anti-diabetic agents. However, side effects and skeletal muscle health are not considered in the treatment for diabetic patients. Recently, natural compounds have been proven to inhibit DPP-4 with fewer side effects. In this work, initially, molecular docking simulations revealed that a natural compound, Galangin, possess a binding energy of -24 KJ/mol and interaction residues SER 630 and TYR 547, that are responsible for potent DPP-4 inhibition. In vitro studies showed that galangin not only inhibits DPP-4 in a concentration-dependent manner but also regulates glucose levels, enabling the prolInternational journal of molecular sciencesE1228https://www.ebi.ac.uk/biostudies/studies/S-EPMC6429117biostudies-literatureDiscovery of Galangin as a Potential DPP-4 Inhibitor That Improves Insulin-Stimulated Skeletal Muscle Glucose Uptake: A Combinational Therapy for Diabetes.PMC6429117Gallardo-Velazquez TChittepu VCSROsorio-Revilla GKalhotra PfalseDiscovery of Galangin as a Potential DPP-4 Inhibitor That Improves Insulin-Stimulated Skeletal Muscle Glucose Uptake: A Combinational Therapy for Diabetes.Dipeptidyl peptidase-4 (DPP-4) is a well-known therapeutic drug target proven to reduce blood glucose levels in diabetes mellitus, and clinically, DPP-4 inhibitors are used in combination with other anti-diabetic agents. However, side effects and skeletal muscle health are not considered in the treatment for diabetic patients. Recently, natural compounds have been proven to inhibit DPP-4 with fewer side effects. In this work, initially, molecular docking simulations revealed that a natural compound, Galangin, possess a binding energy of -24 KJ/mol and interaction residues SER 630 and TYR 547, that are responsible for potent DPP-4 inhibition. In vitro studies showed that galangin not only inhibits DPP-4 in a concentration-dependent manner but also regulates glucose levels, enabling the prol2019-01-01T00:00:00Z2019 Mar2026-04-30T23:55:33.574Z2025-05-29T22:08:06.681ZS-EPMC64291173086210410.3390/ijms20051228