Injection of YiQiFuMai powder protects against heart failure via inhibiting p38 and ERK1/2 MAPKs activation

Injection of YiQiFuMai (YQFM) powder, a modern Chinese plant-derived medical preparation, has a therapeutic effect in heart failure (HF). However, its therapeutic mechanism remains largely unknown. To investigate the molecular mechanisms of YQFM in HF. Kinase inhibition profiling assays with 2 mg/mL YQFM were performed against a series of 408 kinases. In addition, the effects of kinase inhibition were validated in cardiomyocyte cell line H9c2. <i>In vivo</i>, HF with reduced ejection fraction (HFrEF) was induced by permanent left anterior descending (LAD) coronary artery ligation for 6 weeks in male Sprague-Dawley rats. Then, HFrEF mice were treated with 0.46 g/kg YQFM or placebo once a day for 2 weeks. Echocardiography, immunohistochemistry, histological staining and Western blotting analysis were performed to assess the myocardial damage and molecular mechanisms. Kinase inhibition profiling analysis demonstrated that mitogen-activated protein kinases (MAPKs) mediated the signalling cascades of YQFM during HF therapy. Meanwhile, p38 and extracellular signal-regulated kinases (ERK1/2) were inhibited after YQFM treatment in H9c2 cells. In rats, the control group had lower left ventricular ejection fraction (LVEF) at 37 ± 1.7% compared with the YQFM group at 54 ± 1.1% (<i>p</i> &lt; 0.0001). Cardiac fibrosis levels in control group rats were significantly higher than YQFM group (30.5 ± 3.0 vs. 14.1 ± 1.0, <i>p</i> &lt; 0.0001). Our collective <i>in vitro</i> and <i>in vivo</i> experiments demonstrated that YQFM improves left ventricular (LV) function and inhibits fibrosis in HFrEF rats by inhibiting MAPK signalling pathways.