Tongguan capsule for treating Myocardial Ischemia-Reperfusion Injury: Integrating Network Pharmacology and Mechanism Study

Abstract Purpose Tongguan Capsule (TGC) is widely used in the treatment of coronary atherosclerotic disease and heart failure after myocardial infarction; yet, the exact mechanism of action is still unclear. In this study, network pharmacology and experimental validation were used to examine the mechanism of TGC prescription in the treatment of myocardial ischemia-reperfusion injury (MIRI). Methods The components of TGC and candidate targets for MIRI therapy were searched through multiple databases. ClueGO plug-in of Cytoscape was used for enrichment analysis. The binding ability of components to the target was determined by molecular docking.Finally, MIRI model in vivo and hypoxia/reoxygenation (H/R) model in vitro were established for verification. Results Molecular docking results suggested that components such as kaempferol, kaempferol, luteolin, tanshinone IIA had a high affinity with autophagy-related proteins in the mTOR pathway. Further in vivo testing indicated that TGC could improve cardiac function and reduce infarct size in a MIRI mouse model. In vitro experiments also suggested that TGC inhibited H/R cell apoptosis by increasing the levels of GSK-3β, LC3, and Beclin1, and by decreasing the expression of mTOR and p62. Conclusion To sum up, these data indicated that TGC could protect the heart from MIRI by upregulating autophagy.