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

Abstract

Context 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. Objective To investigate the molecular mechanisms of YQFM in HF. Materials and methods 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. In vivo , 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. Results 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% ( p < 0.0001). Cardiac fibrosis levels in control group rats were significantly higher than YQFM group (30.5 ± 3.0 vs. 14.1 ± 1.0, p < 0.0001). Conclusions Our collective in vitro and in vivo experiments demonstrated that YQFM improves left ventricular (LV) function and inhibits fibrosis in HFrEF rats by inhibiting MAPK signalling pathways.

YiQiFuMai Injection Ameliorated Sepsis-induced Cardiomyopathy by Inhibition of Ferroptosis via xCT/GPX4 Axis

“…H9c2 cells were cultured in DMEM supplemented with 10% FBS in a humid environment with a constant temperature of 37°C and a composition of 5% CO 2 and 95% air. The culture medium was refreshed every alternate day, and cell passages were performed when they attained 80%-90% confluency (20).…”