title: Cardioprotective effects of the YiQiFuMai injection and isolated compounds on attenuating chronic heart failure via NF-κB inactivation and cytokine suppression.
abstract: BACKGROUND
  The YiQiFuMai injection (YQFM) is a traditional Chinese medicine for the treatment of chronic heart failure (CHF). The present study not only evaluated the cardioprotective effect and anti-inflammatory mechanism of the YQFM injection in an experimental model of CHF but also investigated its bioactive constituents in vitro.
  
  
  METHODS
  The left anterior descending coronary artery (LAD) in rats was ligated to make an animal model of CHF. From this, electrocardiographic parameters and exterior signs of rat hearts were recorded. Additionally, the histopathology of heart tissues was examined, and parameters of inflammatory stress were measured. Experiments were performed over two months in LAD-ligation rats treated with YQFM or vehicle. Treatment with Captopril was used as a positive control, which has previously been shown to prevent CHF, and rats without LAD-ligation were used as a negative control. Furthermore, we screened and identified potential anti-inflammatory constituents by ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC/Q-TOF-MS) combined with NF-κB activity luciferase reporter assay systems. Further cytokine detection confirmed the anti-inflammatory effects of the potential NF-κB inhibitors from YQFM.
  
  
  RESULTS
  The administration of YQFM significantly improved cardiac function and ameliorated the activity level of inflammatory mediators (such as tumor necrosis factor-alpha, interleukin-6, and interleukin-1β) in CHF rats. Eight potential anti-inflammatory ingredients, ginsenosides Rb1, Rg1, Rf, Rh1, Rc, Rb2, Ro, and Rg3, were characterized and confirmed. Among these compounds, ginsenoside Ro was revealed as a new NF-κB inhibitor.
  
  
  CONCLUSIONS
  The results suggested that NF-κB inactivation and cytokine suppression might be one of the main mechanisms of YQFM that caused ameliorative effects in CHF rats, and the major constituents of ginsenosides were identified playing a key role in the treatment of CHF.
authors.affiliation: College of Pharmacy, State Key Laboratory of Medicinal Chemical Biology, Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin 300071, People's Republic of China.
authors.forename: Lu
authors.initials: L
authors.lastname: Xing
authors.forename: Min
authors.initials: M
authors.lastname: Jiang
authors.forename: Linyi
authors.initials: L
authors.lastname: Dong
authors.forename: Jie
authors.initials: J
authors.lastname: Gao
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Hou
authors.forename: Gang
authors.initials: G
authors.lastname: Bai
authors.forename: Guoan
authors.initials: G
authors.lastname: Luo
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002316:Cardiotonic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000378:metabolism; D004365:Drugs, Chinese Herbal / Q000494:pharmacology* / Q000627:therapeutic use; D036145:Ginsenosides / Q000494:pharmacology* / Q000627:therapeutic use; D057809:HEK293 Cells; D006333:Heart Failure / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D008297:Male; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000893:Anti-Inflammatory Agents; D002316:Cardiotonic Agents; D016207:Cytokines; D004365:Drugs, Chinese Herbal; D036145:Ginsenosides; D016328:NF-kappa B; C584693:yi-qi-fu-mai