Characterization of the effects of oxymatrine on myocardial hypertrophy in spontaneously hypertensive rats through transcriptomics and metabolomics

Cardiac hypertrophy is a cardiac structural remodeling and dysfunction resulting from chronic hypertension and is an independent risk factor for cardiovascular morbidity and mortality. Oxymatrine (OMT), an alkaloid extracted from the traditional Chinese medicine Sophora flavescens, can ameliorate cardiac hypertrophy and heart failure. However, the underlying mechanisms remain unclear. In this study, we investigated the underlying mechanism of OMT on cardiac hypertrophy in spontaneously hypertensive rats (SHRs). Echocardiography was used to assess cardiac function of SHRs. Wheat germ agglutinin (WGA) and Masson staining were employed to evaluate the effects of OMT on cardiac fibrosis and cardiomyocyte hypertrophy in SHRs. Transcriptomics and metabolomics were performed to explore the underlying mechanisms of OMT's improvement of cardiac hypertrophy. The results were further verified by RT-qPCR, immunohistochemistry, and ELISA. The results show that OMT significantly alleviates myocardial hypertrophy and improves myocardial remodeling in SHRs, as evidenced by reduced left ventricular wall thickness, myocardial enlargement and collagen deposition. Transcriptomic analysis revealed that OMT reversed the expression of 10 genes associated with linoleic acid/arachidonic acid metabolism, cytochrome P450, steroid hormone biosynthesis, and myocardial adrenergic signaling. Metabolomic analysis indicated that OMT reversed the levels of 16 metabolites related to steroid hormone biosynthesis, aldosterone synthesis and secretion, and tryptophan metabolism. Integrated analysis revealed that the gene Cyp2e1 and the metabolite desoxycortone (DOC) were enriched in overlapping transcriptomic and metabolomic KEGG pathways, and both were reversed by OMT treatment. Our study underscores the potential molecular and metabolic mechanisms of OMT against pressure overload-induced myocardial hypertrophy and provides theoretical support for its exploration in other indications.