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

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 −253.08 kJ mol −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.