Exploring the Underlying Mechanism of Alpinia officinarum Hance Ameliorating Diabetic Gastroparesis through Combining Network Pharmacology, Molecular Docking, and in Vivo Experimental Verification

Background: Alpinia officinarum Hance (AOH) has a long history in China as a Chinese medicine and exerts the pharmacological effects of antidiabetic and gastrointestinal protection. In traditional Chinese medicine theory, AOH is often combined with other Chinese medicines for the treatment of diabetic gastroparesis (DGP). However, the molecular mechanisms, potential targets, and bioactive ingredients of AOH that act against DGP are yet to be elucidated. In this study, network pharmacology, molecular docking, and experimental study were used to predict the therapeutic effects and the potential molecular mechanism of AOH in DGP. Methods: Network pharmacology analysis was performed to acquire information on the active chemical ingredients, DGP-related target proteins in AOH, and potential signaling pathway. In addition, molecular docking approach was used to simulate the binding of drugs and targets. Finally, DGP-mice model was used for experimental verification in vivo. Results: Through the network pharmacological research, AKT1 was found to be the core protein in AOH for the treatment of DGP and was mainly involved in the PI3K-AKT signaling pathway. Additionally, the interactions between bioactive compounds and target proteins (PIK3CA and AKT1) were analyzed using molecular docking, which verified the results of network pharmacology. Further in vivo studies indicated that AOH could reduce fasting blood glucose levels, improve gastric emptying rate, and ameliorate biochemical indicators in DGP mice. Moreover, AOH could increase the expressions and phosphorylation levels of PI3K and AKT in the stomach to regulate oxidative stress. Conclusions: The study has shown that AOH may play a protective role on DGP through mediation of the PI3K-AKT signaling pathway to regulate oxidative stress.