title: Notoginsenoside R1 attenuates cardiac dysfunction in endotoxemic mice: an insight into oestrogen receptor activation and PI3K/Akt signalling.
abstract: OBJECTIVE
  Notoginsenoside R1 (NG-R1), a novel phytoestrogen isolated from Panax notoginseng, is believed to have anti-inflammatory, anti-oxidative and anti-apoptotic properties. However, its cardioprotective properties and underlying mechanisms are largely unknown. Here we have assessed the contribution of the anti-inflammatory effects of NG-R1 to the amelioration of septic cardiac dysfunction and inflammation in mice.
  
  
  METHODS
  We assessed cardiac function in mice by echocardiography. We studied the protein or mRNA levels of some inflammatory factors, apoptotic factors and oestrogen receptors (ERs) in heart tissues upon stimulation with bacterial LPS, NG-R1 or some pharmacological inhibitors.
  
  
  RESULTS
  Six hours after LPS administration (10 mg·kg(-1) , i.p.) cardiac function was decreased, an effect attenuated by NG-R1 pretreatment (25 mg·kg(-1) ·d(-1) , i.p.). NG-R1 also improved the imbalance between iNOS and eNOS, prevented activation of NF-κB and the subsequent myocardial inflammatory and apoptotic responses in endotoxemic mice. The effects of NG-R1 were closely associated with activation of the oestrogen receptor ERα and of PI3K/PKB (Akt) signalling, as characterized by NG-R1-induced preservation in ERα, phospho-Akt, phospho-GSK3β and I-κBα, and of cardiac function that was partially blocked by selective inhibitors of ERα or PI3K. However, NG-R1 had no effect on LPS-activated TLR-4.
  
  
  CONCLUSIONS
  NG-R1 is a promising compound for protecting the heart from septic shock, possibly via the activation of ERα and PI3K/Akt signalling. This mechanism produces blockade of NF-κB activation and attenuation of the pro-inflammatory state and apoptotic stress in the myocardium.
authors.affiliation: Research Center for Pharmacology and Toxicology, Institute of Medicinal Plant Development (IMPLAD), Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China. bsun@implad.ac.cn
authors.forename: Bing
authors.initials: B
authors.lastname: Sun
authors.forename: Jing
authors.initials: J
authors.lastname: Xiao
authors.forename: Xiao-Bo
authors.initials: XB
authors.lastname: Sun
authors.forename: Ying
authors.initials: Y
authors.lastname: Wu
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism; D019446:Endotoxemia / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D047628:Estrogen Receptor alpha / Q000378:metabolism*; D005786:Gene Expression Regulation; D036145:Ginsenosides / Q000494:pharmacology* / Q000627:therapeutic use; D006321:Heart / Q000187:drug effects / Q000503:physiopathology; D007249:Inflammation / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D051379:Mice; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D016328:NF-kappa B / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines; D047628:Estrogen Receptor alpha; D036145:Ginsenosides; D008070:Lipopolysaccharides; D016328:NF-kappa B; D012333:RNA, Messenger; D019001:Nitric Oxide Synthase; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; C072936:notoginsenoside R1