Exploring the Hypoglycaemic Mechanism of Chinese Medicine Xiao‐Ke‐An Based on Target Dipeptidyl Peptidase 4 Using Molecular Docking and Dynamics Simulation

Abstract

Xiao-Ke-An is a traditional Chinese medicine formula for reducing the effects of diabetes by inhibiting dipeptidyl peptidase-4 (DPP-4) activity. However, its molecular mechanism is unclear owing to the complexity of its components. In this study, methods of molecular docking, molecular dynamics and molecular mechanics/Poisson Boltzmann surface area are combined for analysis. The main hypoglycaemic mechanism of Xiao-Ke-An involves multiple components. In particular, MOL003714 shows the strongest binding capacity with a binding free energy of À 253.08 kJ mol À 1 and thus could be a potent inhibitor of DPP-4. Additionally, MOL007062 and MOL010404 show strong interactions with superoxide dismutase, tumour necrosis factor-alpha and caspase-3, indicating their ability to decrease the symptoms of type II diabetes by alleviating insulin resistance and reducing inflammatory reactions and oxidative stress. This study provides a theoretical basis for the discovery and modification of natural DPP-4 inhibitors and details the role of Xiao-Ke-An.