Shenfu injection combats pathological myocardial hypertrophy by targeting <i>TNF</i> and <i>TGFB1</i> to inhibit angiotensin II-induced autophagy

Abstract Objectives This study aimed to explore the mechanism of action of Shenfu injection (SFI) on pathological myocardial hypertrophy. Methods The compound targets of the active ingredients in SFI were collected and intersected with the gene targets related to pathological myocardial hypertrophy. We performed protein-protein interactions (PPI), network construction, KEGG pathway enrichment analysis, and molecular docking on these targets. We used RT-qPCR and Western blot to measure the number of related genes and proteins and analyze their mechanisms of action. Results SFI relieved the hypertrophy of H9C2 cells induced by angiotensin II (Ang II). Eleven possible targets of SFI against myocardial hypertrophy were obtained. After conducting KEGG pathway enrichment analysis, these genes are closely related to heart disease-related pathways. SFI reversed the increase in the expression levels of TNF , TGFB1 , mTORC1 , and p-ULK1-Ser555 caused by Ang II. SFI can reduce the Ang II-induced increase in LC3-positive cells. Conclusions Our findings demonstrate that SFI inhibits Ang II-induced myocardial hypertrophy by attenuating pathological autophagy, an effect mediated through targeting TNF and TGFB1 pathways. These results position SFI as a promising multi-target therapeutic strategy targeting dysregulated cytokine signaling and autophagy in cardiac remodeling.