Molecular mechanisms of suxiao jiuxin pills in ameliorating post-acute myocardial infarction inflammatory response: a combined network pharmacology, Mendelian randomization, and experimental validation study

Abstract

Purpose In recent years, Suxiao Jiuxin Pill (SJP) has emerged as a potential treatment for various cardiovascular diseases, the exact molecular mechanisms remain poorly characterized. Consequently, this study seeks to investigate the target genes associated with SJP's active components in AMI, as well as the underlying biological processes, utilizing network pharmacology (NP) and Mendelian randomization (MR) analysis. Methods To unravel SJP's targets and its regulatory mechanisms against AMI, we combined NP, MR, and molecular docking strategies. A rat MI model was established by ligating the LAD coronary artery at the designated site. PCR and immunofluorescent labeling were applied to ovserve the expression of NAMPT and FOS. Results Totally 44 DE-TGs were gained by intersecting 689 DEGs and 969 predicted target genes. Next, two key target genes, NAMPT and FOS, showing markedly upregulated expression in AMI samples. Observations showed that these genes were co-enriched in the “Leishmania Infection” and “Chemokine Signaling Pathway”. Moreover, these key target genes showed robust associations with various immune cells, of which NAMPT exhibited a strong positive correlation with neutrophils (cor = 0.65). Molecular docking revealed NAMPT bound to oleic acid (−5.9 kcal/mol) and FOS bound to pentadecanol (−5.4 kcal/mol). The PCR and immunofluorescence assay results showed that FOS was consistent with the predicted results. Echocardiographic assessments and inflammatory factor expression analyses confirmed that SJP ameliorated cardiac function and alleviated the inflammatory response in MI rats. Conclusion This work further delivers a fresh conceptual framework for deciphering the mechanistic basis of SJP's clinical utility in AMI management.