title: Mechanisms of Chinese Medicine Xinmailong's protection against heart failure in pressure-overloaded mice and cultured cardiomyocytes.
abstract: Patients with heart failure (HF) have high mortality and mobility. Xinmailong (XML) injection, a Chinese Medicine, is clinically effective in treating HF. However, the mechanism of XML's effectiveness on HF was unclear, and thus, was the target of the present study. We created a mouse model of pressure-overload-induced HF with transverse aortic constriction (TAC) surgery and compared among 4 study groups: SHAM (n = 10), TAC (n = 12), MET (metoprolol, positive drug treatment, n = 7) and XML (XML treatment, n = 14). Dynamic changes in cardiac structure and function were evaluated with echocardiography in vivo. In addition, H9C2 rat cardiomyocytes were cultured in vitro and the phosphorylation of ERK1/2, AKT, GSK3β and protein expression of GATA4 in nucleus were detected with Western blot experiment. The results showed that XML reduced diastolic thickness of left ventricular posterior wall, increased ejection fraction and fraction shortening, so as to inhibit HF at 2 weeks after TAC. Moreover, XML inhibited the phosphorylation of ERK1/2, AKT and GSK3β, subsequently inhibiting protein expression of GATA4 in nucleus (P < 0.001). Together, our data demonstrated that XML inhibited the TAC-induced HF via inactivating the ERK1/2, AKT/GSK3β, and GATA4 signaling pathway.
authors.affiliation: AMI Key Laboratory of Chinese Medicine, Guangdong Province Academy of Chinese Medicine, Guangdong Province Hospital of Chinese Medicine, 2nd Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510006, China.
authors.forename: Jianyong
authors.initials: J
authors.lastname: Qi
authors.affiliation: Animal Laboratory, Southern Medical University, Guangzhou, 510515, China.|Animal Laboratory, 2nd Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510006, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Yu
authors.affiliation: AMI Key Laboratory of Chinese Medicine, Guangdong Province Academy of Chinese Medicine, Guangdong Province Hospital of Chinese Medicine, 2nd Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510006, China.
authors.forename: Yafang
authors.initials: Y
authors.lastname: Tan
authors.affiliation: AMI Key Laboratory of Chinese Medicine, Guangdong Province Academy of Chinese Medicine, Guangdong Province Hospital of Chinese Medicine, 2nd Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510006, China.
authors.forename: Renshan
authors.initials: R
authors.lastname: Chen
authors.affiliation: Lab of Chinese Materia Medica Preparation, 2nd Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510006, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Xu
authors.affiliation: Puning Hospital of Chinese Medicine, Puning, Guangdong Province, 515300, China.
authors.forename: Yanfen
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Puning Hospital of Chinese Medicine, Puning, Guangdong Province, 515300, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Lu
authors.affiliation: AMI Key Laboratory of Chinese Medicine, Guangdong Province Academy of Chinese Medicine, Guangdong Province Hospital of Chinese Medicine, 2nd Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510006, China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, Northeast Ohio Medical University, Rootstown, Ohio, 44272, USA.
authors.forename: Jiashin
authors.initials: J
authors.lastname: Wu
authors.affiliation: Animal Laboratory, Southern Medical University, Guangzhou, 510515, China.
authors.forename: Weiwang
authors.initials: W
authors.lastname: Gu
authors.affiliation: AMI Key Laboratory of Chinese Medicine, Guangdong Province Academy of Chinese Medicine, Guangdong Province Hospital of Chinese Medicine, 2nd Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510006, China.
authors.forename: Minzhou
authors.initials: M
authors.lastname: Zhang
mesh_terms: D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003251:Constriction, Pathologic; D004195:Disease Models, Animal; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage* / Q000494:pharmacology; D004452:Echocardiography; D050485:GABA Plasma Membrane Transport Proteins / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D000071679:Glycogen Synthase Kinase 3 beta / Q000378:metabolism; D006333:Heart Failure / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects; D051379:Mice; D032383:Myocytes, Cardiac / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats
chemical_list: D004365:Drugs, Chinese Herbal; D050485:GABA Plasma Membrane Transport Proteins; D000071679:Glycogen Synthase Kinase 3 beta; D051057:Proto-Oncogene Proteins c-akt; C079264:Slc6a11 protein, mouse; C000618382:xinmailong; C000605507:Gsk3b protein, mouse