title: Qishenyiqi Dropping Pill attenuates myocardial fibrosis in rats by inhibiting RAAS-mediated arachidonic acid inflammation.
abstract: BACKGROUND
  In China, Qishenyiqi Dropping Pill (QSDP), a Chinese medicine formula containing Astragalus membranaceus (Fisch.) Bunge, Salvia miltiorrhiza Bunge, Panax notoginseng (Burkill) F.H.Chen and Dalbergia odorifera T.C.Chen, has been used frequently in traditional folk medicine for treatment of coronary heart diseases (CHD) and heart failure (HF).
  
  
  OBJECTIVE
  Previous study has shown that QSDP has definite therapeutic effects on promoting the heart function on CHD patients. The present study was designed to study the anti-fibrosis effects of QSDP on HF rats and to explore the underlying molecular mechanisms.
  
  
  METHODS
  HF rat model was induced by left anterior descending (LAD) coronary artery ligation. Two-dimensional (2D) echocardiography was adopted to evaluate heart functions. Immunohistochemical (IHC) method and Western-blot were used to detect expression of critical proteins in renin-angiotensin-aldosterone system (RAAS) or arachidonic acid (AA) metabolic pathway.
  
  
  RESULTS
  Heart functions were seriously injured in the model group. Expressions of fibrotic markers, such as collagen Ⅰ, collagen Ⅲ, matrix metallopeptidase 2 (MMP2) and MMP9 were elevated in the model group. RAAS pathway was activated. Interestingly, AA pathway was also up-regulated in the model group and it was down-regulated by angiotensin converting enzyme inhibitors (ACEIs) drug Captopril. Expressions of the important signal-transuding proteins, including NF-κB, JAK1/STAT3 and Akt, all increased remarkably in the model group. Treatment with QSDP could attenuate myocardial fibrosis by inhibiting RAAS-activated pathway, as indicated by decreased angiotensin type 1 receptor (AT1) and increased AT2 expression. Expressions of phospholipase A2 (PLA2), cyclooxygenase 1 (COX1) and COX2 were also down-regulated in the QSDP-treated group. In addition, "therapeutic" QSDP administration seemed to down-regulate expressions of NF-κB, JAK1/ STAT3 and Akt which may play important roles in myocardial fibrosis.
  
  
  CONCLUSIONS
  QSDP can exert anti-fibrosis effect by down-regulating RAAS pathway, and subsequently inhibiting expressions of proteins in AA pathway.
authors.affiliation: Modern Research Center for Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, PR China; School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 100102, PR China. Electronic address: wangjing910629@sina.com.
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.affiliation: Basic Medical College, Beijing University of Chinese Medicine, Beijing 100029, PR China. Electronic address: lu-linghui@hotmail.com.
authors.forename: Linghui
authors.initials: L
authors.lastname: Lu
authors.affiliation: Basic Medical College, Beijing University of Chinese Medicine, Beijing 100029, PR China. Electronic address: doctor_wangyong@sina.com.
authors.forename: Yong
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Center of Scientific Experiment, Beijing University of Chinese Medicine, Beijing 100029, PR China. Electronic address: Nayattmm@vip.sina.com.
authors.forename: Yan
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Center of Scientific Experiment, Beijing University of Chinese Medicine, Beijing 100029, PR China. Electronic address: hanjing8585@163.com.
authors.forename: Jing
authors.initials: J
authors.lastname: Han
authors.affiliation: Basic Medical College, Beijing University of Chinese Medicine, Beijing 100029, PR China. Electronic address: wangwei26960@126.com.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: Modern Research Center for Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, PR China. Electronic address: lichun19850204@163.com.
authors.forename: Chun
authors.initials: C
authors.lastname: Li
authors.affiliation: Modern Research Center for Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, PR China. Electronic address: pengfeitu@163.com.
authors.forename: Pengfei
authors.initials: P
authors.lastname: Tu
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use*; D016718:Arachidonic Acid; D024042:Collagen Type I / Q000378:metabolism; D024043:Collagen Type II / Q000378:metabolism; D051545:Cyclooxygenase 1 / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism; D004365:Drugs, Chinese Herbal / Q000494:pharmacology / Q000627:therapeutic use*; D005355:Fibrosis; D006333:Heart Failure / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D053613:Janus Kinase 1 / Q000378:metabolism; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D016328:NF-kappa B / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism; D044139:Receptor, Angiotensin, Type 2 / Q000378:metabolism; D012084:Renin-Angiotensin System / Q000187:drug effects; D050796:STAT3 Transcription Factor / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D024042:Collagen Type I; D024043:Collagen Type II; D004365:Drugs, Chinese Herbal; D008565:Membrane Proteins; D016328:NF-kappa B; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D050796:STAT3 Transcription Factor; C494088:Stat3 protein, rat; C528580:qishen yiqi; D016718:Arachidonic Acid; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496513:Ptgs1 protein, rat; C489691:Ptgs2 protein, rat; C507906:Jak1 protein, rat; D053613:Janus Kinase 1; D051057:Proto-Oncogene Proteins c-akt; D020778:Matrix Metalloproteinase 2; C522363:Mmp2 protein, rat; D020780:Matrix Metalloproteinase 9; C572337:Mmp9 protein, rat
keywords: AA metabolism pathway; Myocardial fibrosis; QSDP; RAAS