YiQiFuMai powder injection ameliorates chronic heart failure through cross-talk between adipose tissue and cardiomyocytes via up-regulation of circulating adipokine omentin.

YiQiFuMai Powder Injection (YQFM) is widely used in clinical practice for the treatment of heart failure (HF). However, its functional molecular mechanism remains to be fully uncovered. Our present study aimed to elucidate the impact of YQFM and underlying mechanisms on coronary artery ligation (CAL)-induced HF. Our results exhibited that YQFM significantly mitigated CAL-induced HF via meliorating the left ventricular contractile function and reducing the serum content of creatine kinase MB (CK-MB), aspartate aminotransferase (AST), interleukin-6 (IL-6), troponin (Tn), myosin, myoglobin (MYO) and myocilin (MYOC). Then, the relevance between circulating omentin level and cardiac function was investigated and we found that serum omentin levels positively associated with ejection fraction and negatively correlated with NT-proBNP content. Further, the effect of YQFM on cardiac function and omentin change in 1, 7 and 14 days CAL-induced HF mice was evaluated and the omentin secretion in isolated subcutaneous (SCAT) and epicardial adipose tissue (EAT) after YQFM treatment were detected. YQFM could increase the circulating omentin content both in 14 days CAL-induced HF mice and isolated EAT. And increased omentin in conditioned medium (CM) could inhibit simulated ischemic/reperfusion (SI/R)-induced cardiomyocytes apoptosis. Moreover, YQFM could ameliorate myocardial apoptosis via positive regulation of AMPK, PI3 K/Akt and negative regulation of MAPKs signaling pathways. Ginsenoside Rd might partially mediated omentin-dependent protective effect of YQFM. Our findings indicated that regulation of cross-talk between adipose tissue and cardiomyocytes might be a potential target through which YQFM exerts cardioprotective effect apart from direct cardiomyocytes protection.

YiQiFuMai Powder Injection attenuates coronary artery ligation-induced myocardial remodeling and heart failure through modulating MAPKs signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: YiQiFuMai Powder Injection (YQFM), a traditional Chinese medicine prescription re-developed based on Sheng-Mai-San, is a classical and traditional therapeutic for clinical heart failure (HF) and angina. However, its potential mechanism against HF remains unclear. AIM OF THE STUDY: The present study observes the therapeutic role of YQFM and mechanisms underlying its effects on coronary artery ligation (CAL)-induced myocardial remodeling (MR) and HF. METHODS: MR and HF were induced by permanent CAL for 2 weeks in ICR mice. Then mice were treated with YQFM (0.13g/kg, 0.26g/kg and 0.53g/kg) once a day until 2 weeks later. Cardiac structure and function were evaluated by echocardiography. Serum lactate dehydrogenase (LDH), creatine kinase (CK) and malondialdehyde (MDA) were measured by biochemical kits and cardiomyocyte morphology was assessed by hematoxylin-eosin (HE) staining. Myocardial hydroxyproline (HYP), serum amino-terminal pro-peptide of pro-collagen type III (PIIINP), and Masson's trichrome staining were employed to evaluate cardiac fibrosis. Circulating level of N-terminal pro-B-type natriuretic peptide (NT-proBNP) was tested by ELISA kit to predict prognosis of CAL-induced HF. Effects of YQFM on the mitogen-activated protein kinases (MAPKs) pathway after CAL operation was evaluated by Western blotting and immunohistochemistry assay. RESULTS: YQFM (0.53g/kg) improved the left ventricular (LV) function and structure impairment after 2 weeks in CAL mice. YQFM administration also decreased LDH and CK activities, circulating levels of MDA, PIIINP, NT-proBNP, and HYP contents. Moreover, YQFM ameliorated cardiac injury and fibrosis. Furthermore, YQFM (0.53g/kg) inhibited the myocardial phosphorylation of MAPKs in HF mice. CONCLUSION: Our findings suggest that YQFM attenuates CAL-induced HF via improving cardiac function, attenuating structure damage, oxidative stress, necrosis, collagen deposition, and fibrosis. In addition, YQFM ameliorates cardiac remodeling and HF, partially through inhibiting the MAPKs signaling pathways. These data provide insights and mechanisms into the widely application of YQFM in patients with HF, MI and other ischemic heart diseases.