Effect of Xuefu Zhuyu Capsule on Myocardial Infarction: Network Pharmacology and Experimental Verification.

BACKGROUND: Myocardial infarction (MI) is the most severe manifestation of cardiovascular disease. Xuefu Zhuyu Capsule (XFC), a proprietary Chinese medicine, is widely used in various cardiovascular diseases. At present, the molecular mechanism of XFC remains unclear. OBJECTIVE: To explore the mechanism of anti-MI effects of XFC by combining network pharmacology and experiments. METHODS: TCMSP, GeneCards, and DisGeNET databases were used to find the target of XFC. PPI analysis was performed by the STRING database. KEGG and GO analyses were performed by Metascape Database. Molecular docking was performed by Autodock Vina. HE staining, echocardiography, immunofluorescence, and TUNEL were performed to verify the prediction results. RESULTS: Network pharmacology showed that quercetin, kaempferol, β-sitosterol, luteolin, and baicalein were the main active ingredients of XFC. TNF, IL6, TP53, VEGFA, JUN, CASP3, and SIRT1 were the main targets of XFC. KEGG results showed that key genes were mainly enriched in lipid and atherosclerosis, PI3K-Akt signaling pathway, MAPK signaling pathway, and NF-κB signaling pathway. HE staining showed that XFC could improve the morphology of myocardial tissue. Echocardiography showed that XFC could improve cardiac function. TUNEL showed that XFC could reduce cardiomyocyte apoptosis. Immunofluorescence showed that XFC could reduce the expression of α-smooth muscle actin (α-SMA) and increase the expression of CD31. In addition, we found that XFC may exert its therapeutic effects through SIRT1. CONCLUSION: This study demonstrated that SIRT1 may be the target of XFC in the treatment of MI. The active ingredients of XFC and SIRT1 can be stably bound. XFC could inhibit apoptosis, promote angiogenesis, and improve myocardial fibrosis through SIRT1.