Optimized new Shengmai powder ameliorates myocardial fibrosis in rats with heart failure by inhibition of the MAPK signaling pathway

Optimized New Shengmai Powder (ONSMP) is a traditional Chinese medicine (TCM) formula for heart failure treatment. MAPK signaling pathway is the key driver of myocardial fibrosis in heart failure. However, the mechanism of ONSMP on myocardial fibrosis and MAPK signaling pathway remains unclear.To evaluate the effect of ONSMP against myocardial fibrosis in heart failure and the underlying mechanisms.Firstly, UHPLC-Q-Exactive-MS/MS was used to identify the active components in ONSMP. Secondly, a rat model of heart failure was established by ligating the left anterior descending branch of the coronary artery. After four weeks of intragastric administration of ONSMP, we used various classic tests, including echocardiography, exhaustive swimming, cardiopulmonary coefficient, heart failure markers, and cardiac pathological section, to assess the prescription's anti-myocardial fibrosis in heart failure properties. AGEs, Ang Ⅱ, VEGF, CTGF, and TGFβ levels in rat serum were quantified using ELISA. The positive expression of p-ERK1/2 and p-JNK1/2 of rat myocardium was determined immunohistochemical. The protein and mRNA levels of genes involved in the MAPK signaling pathway and myocardial fibrosis were measured using western blotting or real-time PCR.The main components of ONSMP that regulate the MAPK signaling pathway are isorhamnetin, kaempferol, quercetin, and tanshinone ⅡA. ONSMP ameliorated cardiac function and exercise tolerance and reduced cardiopulmonary coefficient, heart failure marker levels, and myocardial fibrosis in the heart failure rats. In addition, ONSMP diminished the serum MAPK pathway activator levels, positive expression level of p-ERK1/2 and p-JNK1/2, protein and mRNA levels of components of the MAPK signaling pathway in the myocardial tissue of heart failure rat, indicating that it inhibits MAPK signaling pathway.ONSMP delayed heart failure by inhibiting myocardial fibrosis via the MAPK signaling pathway.