Abstract

Ethnopharmacological relevance: Qifu yixin prescription (QYP), an effective traditional Chinese medicine formula, has been utilized in the clinical treatment of cardiovascular diseases for over two decades and has been granted a national invention patent in China. It has demonstrated the ability to improve clinical symptoms in patients with heart failure. However, its precise effects and underlying molecular mechanisms remain unclear.

Aim of the study: To evaluate the efficacy of QYP in treating HF and the underlying mechanisms.

Materials and methods: The heart failure (HF) model in mice was established using transverse aortic constriction (TAC), while neonatal rat cardiac fibroblasts (CFs) were utilized for in vitro experiments. The bioactive compounds in QYP were identified through high-performance liquid chromatography (HPLC). Cardiac hypertrophy, function, and fibrosis were assessed using morphological observations, echocardiography, and histomorphometric analyses. To investigate the underlying mechanisms by which QYP alleviates HF, transcriptomic analysis was conducted, and network pharmacology was employed to explore its potential mechanisms of action. Mechanistically, the expression levels of sGC, PKG, ERK, and p-ERK were analyzed using western blotting, immunohistochemistry, and immunofluorescence. Molecular docking was conducted to assess the binding affinity of the compounds of QYP to sGC. Additionally, the effects of QYP on CFs were investigated through cell-based assays.

Results: We identified 33 bioactive compounds in QYP. Histomorphometric and transcriptomic analyses indicated that QYP alleviates cardiac fibrosis in HF. Network pharmacological analysis suggested that the sGC/cGMP/PKG and MAPK pathways are key mechanisms underlying the effects of QYP on cardiac fibrosis. The findings confirmed that QYP activates sGC, leading to the inhibition of ERK phosphorylation. Molecular docking revealed that the compounds of QYP exhibit strong binding affinity to sGC. Additionally, cell-based experiments demonstrated that QYP effectively suppresses CFs activation by stimulating sGC.

Conclusions: These results indicate QYP improves cardiac fibrosis in HF by activating sGC to inhibit ERK phosphorylation. We propose that QYP is a potential treatment for HF with anti-fibrotic properties.