title: Astragaloside IV attenuates inflammatory cytokines by inhibiting TLR4/NF-кB signaling pathway in isoproterenol-induced myocardial hypertrophy.
abstract: BACKGROUND
  Astragaloside IV (As IV) is one of the main effective components isolated from the traditional Chinese medical herb Astragalus membranaceus. The protective effect of Astragalus membranaceus on myocardial hypertrophy has been extensively proved. To test the hypothesis that Astragaloside IV can ameliorate the myocardial hypertrophy and inflammatory effect induced by β-adrenergic hyperactivity, we carried out in vivo and in vitro experiments.
  
  
  METHODS
  In in vivo study, the isoproterenol (Iso) (5 mg kg(-1) d(-1)) was used as a model of myocardial hypertrophy by intraperitoneal injection. SD rats were randomly assigned to following six groups: A: the control; B: Iso group; C: Iso plus As IV 20 mg kg(-1) d(-1); D: Iso plus As IV 40 mg kg(-1) d(-1); E: Iso plus As IV 80 mg kg(-1) d(-1); F: Iso plus Propranolol 40 mg kg(-1) d(-1). In in vitro study, cultured neonatal rat cardiomyocytes were pretreated with As IV (3, 10, 30 μ mol L(-1)), Propranolol (2 μ mol L(-1)) and BAY11-7082 (5 μ mol L(-1)) for 30 min, and then incubated with Iso (10 μ mol L(-1)) for 48 h. For the rats in each group, the heart mass index (HMI) and the left ventricular mass index (LVMI) were measured. To measure the transverse diameter of left ventricular myocardial cells (TDM), the hematoxylin-eosin (HE) staining method was applied. In addition, the volume and the total protein content of cardiomyocytes were measured, the mRNA expression of ANP and TLR4 were quantified by RT-PCR, the protein expression of TLR4, IκBα and p65 were quantified by Western blot, and the level of TNF-α and IL-6 were measured by ELISA.
  
  
  RESULTS
  In vivo: Comparing the Iso group to the control, the HMI, LVMI, TDM were significantly increased; the protein expression of TLR4 and p65 were increased, while the IκBα were decreased; the expression of ANP, TLR4 mRNA, and TNF-α, IL-6 in serum were significantly increased. These changes could be partly prevented by As IV and Pro. In vitro: the over-expression of the cell size, total protein content could remarkably down-regulated by As IV and Pro, and the results of RT-PCR, Western blot and ELISA were similar to those of in vivo.
  
  
  CONCLUSIONS
  The results of these studies indicate that Astragaloside IV has good protective effect on myocardial hypertrophy induced by isoproterenol. More specifically, the cardioprotection is related to inhibiting the TLR4/NF-кB signaling pathway and the attenuating inflammatory effect.
authors.forename: Juan
authors.initials: J
authors.lastname: Yang
authors.forename: Hong-Xin
authors.initials: HX
authors.lastname: Wang
authors.forename: Ying-Jie
authors.initials: YJ
authors.lastname: Zhang
authors.forename: Yu-Hong
authors.initials: YH
authors.lastname: Yang
authors.forename: Mei-Li
authors.initials: ML
authors.lastname: Lu
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.forename: Sheng-Tao
authors.initials: ST
authors.lastname: Li
authors.forename: Su-Ping
authors.initials: SP
authors.lastname: Zhang
authors.forename: Guang
authors.initials: G
authors.lastname: Li
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002316:Cardiotonic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002478:Cells, Cultured; D017379:Hypertrophy, Left Ventricular / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism*; D015850:Interleukin-6 / Q000378:metabolism; D007545:Isoproterenol; D008297:Male; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012503:Saponins / Q000494:pharmacology* / Q000627:therapeutic use; D015398:Signal Transduction; D051197:Toll-Like Receptor 4 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D014315:Triterpenes / Q000494:pharmacology* / Q000627:therapeutic use; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D002316:Cardiotonic Agents; D015850:Interleukin-6; D016328:NF-kappa B; D012503:Saponins; C495347:Tlr4 protein, rat; D051197:Toll-Like Receptor 4; D014315:Triterpenes; D014409:Tumor Necrosis Factor-alpha; C052064:astragaloside A; D007545:Isoproterenol