title: Coptisine protects rat heart against myocardial ischemia/reperfusion injury by suppressing myocardial apoptosis and inflammation.
abstract: OBJECTIVE
  Protecting the heart from myocardial ischemia and reperfusion (I/R) damage is the focus of intense research. Coptisine is an isoquinoline alkaloid isolated from Coptidis Rhizoma. The present study investigated the potential effect of coptisine on myocardial I/R damage in rats and the underlying mechanisms.
  
  
  RESULTS
  Electrocardiogram examination showed that the administration of coptisine 10 min before ischemia significantly decreased I/R-induced arrhythmia after 30 min ischemia followed by 3 h reperfusion. The release of cardiac markers was also limited. Echocardiography was performed before ischemia and 24 h post-I/R, separately. The M-mode records showed that the reductions of ejection fraction (EF) and fractional shortening (FS) were attenuated in coptisine-treated rats compared with the I/R rats. Similar results were obtained with Evans Blue/triphenyl tetrazolium chloride (TTC) staining, in which coptisine notably reduced infarct size. Moreover, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay demonstrated coptisine suppressed myocardial apoptosis, which may be related to the upregulation of Bcl-2 protein and inhibition of caspase-3 activation. Coptisine treatment also attenuated the proinflammatory cytokines including interleukin (IL)-1β, IL-6, and tumor necrosis factor-α in heart tissue. Additionally, Western blot and immunohistochemical analysis showed that coptisine markedly reduced Rho, Rho-kinase 1 (ROCK1), and ROCK2 expression and attenuated the phosphorylation of myosin phosphatase targeting subunit-1, a downstream target of ROCK.
  
  
  CONCLUSIONS
  Coptisine exerts pronounced cardioprotection in rats subjected to myocardial I/R likely through suppressing myocardial apoptosis and inflammation by inhibiting the Rho/ROCK pathway.
authors.affiliation: Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China; State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, China. Electronic address: gjing_new@126.com.
authors.forename: Jing
authors.initials: J
authors.lastname: Guo
authors.forename: Shou-Bao
authors.initials: SB
authors.lastname: Wang
authors.forename: Tian-Yi
authors.initials: TY
authors.lastname: Yuan
authors.forename: Yu-Jie
authors.initials: YJ
authors.lastname: Wu
authors.forename: Yu
authors.initials: Y
authors.lastname: Yan
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.forename: Xiao-Na
authors.initials: XN
authors.lastname: Xu
authors.forename: Li-Li
authors.initials: LL
authors.lastname: Gong
authors.forename: Hai-Lin
authors.initials: HL
authors.lastname: Qin
authors.forename: Lian-Hua
authors.initials: LH
authors.lastname: Fang
authors.forename: Guan-Hua
authors.initials: GH
authors.lastname: Du
mesh_terms: D000818:Animals; D017209:Apoptosis; D001599:Berberine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D004562:Electrocardiography; D004797:Enzyme-Linked Immunosorbent Assay; D006321:Heart / Q000187:drug effects*; D007249:Inflammation; D009203:Myocardial Infarction / Q000188:drug therapy; D015428:Myocardial Reperfusion Injury / Q000473:pathology*; D009206:Myocardium / Q000473:pathology*; D032383:Myocytes, Cardiac / Q000166:cytology; D051381:Rats; D013696:Temperature; D013997:Time Factors; D054460:rho-Associated Kinases / Q000378:metabolism
chemical_list: D016207:Cytokines; C034384:coptisine; D001599:Berberine; D054460:rho-Associated Kinases
keywords: Apoptosis; Coptisine; Inflammation; Ischemia/reperfusion (I/R); Rho-kinase (ROCK)