Shenmai injection improves lipid metabolism in post-myocardial infarction heart failure based on network pharmacology and experimental validation

Background: Shenmai injection (SMI), a traditional Chinese medicine formulation derived from the herbal decoction Shenmai Yin, is widely used in treating cardiovascular disorders. This study extensively investigated the effects and mechanisms of action of SMI on lipid metabolism in post-myocardial infarction heart failure (pMIHF).

Methods: Network pharmacology was employed to predict the key targets and associated pathways involved in lipid metabolism for potential SMI treatments in post-myocardial infarction heart failure (pMIHF). Subsequently, a pMIHF mouse model and an ischemia/reperfusion (I/R) cell model were established to delve deeper into and validate the underlying mechanism of action.

Results: We performed network pharmacology analysis, which identified 48 active components in SMI and 201 common gene targets. Subsequent screening using the protein-protein interaction network identified 26 core targets, including interleukin (IL)-6, tumor necrosis factor (TNF)-α, Peroxisome Proliferator-activated Receptor alpha (PPARα), and Sirtuin 1 (SIRT1). Based on Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses, we predicted that SMI might act on lipid metabolism in pMIHF through the PPARα pathway, a hypothesis supported by the strong binding affinity between this receptor and the active components of SMI, as confirmed via molecular docking. In a left anterior descending artery-ligation mouse model, SMI significantly improved cardiac function, reduced serum free fatty acid levels, decreased inflammatory cell infiltration and myocardial fibrosis, and maintained myocardial mitochondrial morphology. In ischemia-reperfusion (I/R) cells, SMI reduced cell Apoptosis, improved mitochondrial membrane potential, and decreased mRNA expression levels of IL-6 and TNF-α, while increasing protein levels of PPARα, SIRT1, and PPARα co-activator-1 alpha (PGC1α).

Conclusion: Collectively, our findings suggest that SMI enhances myocardial lipid metabolism and ameliorates pMIHF by upregulating the PPARα/SIRT1/PGC1α pathway.

Lipid metabolism; Peroxisome proliferator-activated receptor alpha; Post-myocardial infarction heart failure; Shenmai injection; network pharmacology.