title: YiQiFuMai Powder Injection attenuates coronary artery ligation-induced myocardial remodeling and heart failure through modulating MAPKs signaling pathway.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Jiangsu Key Laboratory of TCM Evaluation and Translational Research, Department of Complex Prescription of TCM, China Pharmaceutical University, 639 Longmian Road, Nanjing 211198, PR China.
authors.forename: Li-Zhi
authors.initials: LZ
authors.lastname: Pang
authors.affiliation: Department of Technology Development, TianJin Tasly Pride Pharmaceutical Co., Ltd., Tianjin 300410, China.
authors.forename: Ai-Chun
authors.initials: AC
authors.lastname: Ju
authors.affiliation: Jiangsu Key Laboratory of TCM Evaluation and Translational Research, Department of Complex Prescription of TCM, China Pharmaceutical University, 639 Longmian Road, Nanjing 211198, PR China.
authors.forename: Xian-Jie
authors.initials: XJ
authors.lastname: Zheng
authors.affiliation: Jiangsu Key Laboratory of TCM Evaluation and Translational Research, Department of Complex Prescription of TCM, China Pharmaceutical University, 639 Longmian Road, Nanjing 211198, PR China.
authors.forename: Fang
authors.initials: F
authors.lastname: Li
authors.affiliation: Jiangsu Key Laboratory of TCM Evaluation and Translational Research, Department of Complex Prescription of TCM, China Pharmaceutical University, 639 Longmian Road, Nanjing 211198, PR China.
authors.forename: Yun-Fei
authors.initials: YF
authors.lastname: Song
authors.affiliation: Jiangsu Key Laboratory of TCM Evaluation and Translational Research, Department of Complex Prescription of TCM, China Pharmaceutical University, 639 Longmian Road, Nanjing 211198, PR China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Jiangsu Key Laboratory of TCM Evaluation and Translational Research, Department of Complex Prescription of TCM, China Pharmaceutical University, 639 Longmian Road, Nanjing 211198, PR China.
authors.forename: Yuan-Feng
authors.initials: YF
authors.lastname: Gu
authors.affiliation: Jiangsu Key Laboratory of TCM Evaluation and Translational Research, Department of Complex Prescription of TCM, China Pharmaceutical University, 639 Longmian Road, Nanjing 211198, PR China.
authors.forename: Fei-Leng
authors.initials: FL
authors.lastname: Chen
authors.affiliation: Guizhou Provincial Key Laboratory of Pharmaceutics, Guizhou Medical University, Guiyang 550004, Guizhou, China.
authors.forename: Chun-Hua
authors.initials: CH
authors.lastname: Liu
authors.affiliation: Jiangsu Key Laboratory of TCM Evaluation and Translational Research, Department of Complex Prescription of TCM, China Pharmaceutical University, 639 Longmian Road, Nanjing 211198, PR China.
authors.forename: Jin
authors.initials: J
authors.lastname: Qi
authors.affiliation: Department of Medicine-Ather&Lipo, Baylor Colledge of Medicine, One Baylor Plaza, Houston 77030, TX, USA.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Gao
authors.affiliation: Jiangsu Key Laboratory of TCM Evaluation and Translational Research, Department of Complex Prescription of TCM, China Pharmaceutical University, 639 Longmian Road, Nanjing 211198, PR China. Electronic address: junpingkou@cpu.edu.cn.
authors.forename: Jun-Ping
authors.initials: JP
authors.lastname: Kou
authors.affiliation: Jiangsu Key Laboratory of TCM Evaluation and Translational Research, Department of Complex Prescription of TCM, China Pharmaceutical University, 639 Longmian Road, Nanjing 211198, PR China. Electronic address: boyangyu59@163.com.
authors.forename: Bo-Yang
authors.initials: BY
authors.lastname: Yu
mesh_terms: D000818:Animals; D003331:Coronary Vessels / Q000503:physiopathology*; D003402:Creatine Kinase / Q000378:metabolism; D004338:Drug Combinations; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D004452:Echocardiography; D006333:Heart Failure / Q000000981:diagnostic imaging / Q000503:physiopathology* / Q000517:prevention & control*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008026:Ligation; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D008297:Male; D008516:Medicine, Chinese Traditional; D051379:Mice; D008813:Mice, Inbred ICR; D009206:Myocardium / Q000378:metabolism; D011208:Powders; D020257:Ventricular Remodeling / Q000187:drug effects*
chemical_list: D004338:Drug Combinations; D004365:Drugs, Chinese Herbal; D011208:Powders; C009252:fructus schizandrae, radix ginseng, radix ophiopogonis drug combination; D007770:L-Lactate Dehydrogenase; D003402:Creatine Kinase
keywords: Ginsenoside Rc (PubChem CID: 100018); Ginsenoside Re (PubChem CID: 73149); Ginsenoside Rf (PubChem CID: 441922); Heart failure; MAPKs; Myocardial remodeling; Notoginsenoside R2 (PubChem CID: 21599925); Schisandrol A (PubChem CID: 11102092); Schizandrin B (PubChem CID: 108130); Sheng-mai-san; YiQiFuMai powder injection (YQFM)