title: Oral sophocarpine protects rat heart against pressure overload-induced cardiac fibrosis.
abstract: BACKGROUND
  Sophocarpine, a tetracyclic quinolizidine alkaloid, is one of the most abundant active ingredients in Sophora alopecuroides Linn. (Kudouzi). Sophocarpine injection was found to have significant antiviral effects against coxsackievirus B3 and therapeutic effects for viral myocarditis in the clinic.
  
  
  OBJECTIVE
  This study assessed the effects of sophocapine on overload-induced cardiac fibrosis and investigated potential mechanisms.
  
  
  METHODS
  Adult male Sprague-Dawley rats were subjected to a suprarenal abdominal aorta constriction (AC) or sham to induce sustained pressure overload. Six weeks later, rats were randomly assigned to receive sophocapine (10, 20, and 40 mg/kg, gavage) or vehicle treatment for an additional 6 weeks. Six weeks after treatment, cardiac dysfunction, cardiac coefficient, cardiac fibrosis, hydroxyproline concentration, and inflammation mediators were examined.
  
  
  RESULTS
  When compared with the model group, the left ventricular weight/body weight decreased by 25.4% and 39.0% in 20 and 40 mg/kg sophocarpine groups, respectively. The beneficial effects were associated with amelioration of left ventricular systolic pressure (LVSP) and left ventricular enddiastolic pressure (LVEDP). Moreover, pressure overload-induced cardiac fibrosis was attenuated in sophocarpine treated groups. Importantly, sophocarpine (20 and 40 mg/kg) decreased pro-inflammatory cytokine levels (IL-6, 14.6% and 18.5%; IL-1β, 23.1% and 32.6%), collagen content (27.7% and 50.1%), as well as matrix metalloproteinases-2, 9 (MMP-2, 9) expression (MMP-2, 11.8% and 18.5%; MMP-9, 16.2% and 21.1%). Sophocarpine (40 mg/kg) inhibited IκB-α phosphorylation (19.0%).
  
  
  CONCLUSIONS
  These findings indicated that sophocarpine potentially had antifibrotic effects. The mechanism might be due to modulation of the balance between pro-inflammatory cytokine expression and collagen content level as well as MMPs expression via the NF-κB signaling pathway.
authors.affiliation: Department of Cardiology, Qilu Hospital, Shandong University , Jinan , PR China and.
authors.forename: Jun
authors.initials: J
authors.lastname: Li
authors.forename: Liudong
authors.initials: L
authors.lastname: Li
authors.forename: Hongxia
authors.initials: H
authors.lastname: Chu
authors.forename: Xiaojian
authors.initials: X
authors.lastname: Sun
authors.forename: Zhiming
authors.initials: Z
authors.lastname: Ge
mesh_terms: D000284:Administration, Oral; D000470:Alkaloids / Q000008:administration & dosage*; D000818:Animals; D002316:Cardiotonic Agents / Q000008:administration & dosage*; D005355:Fibrosis / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D008297:Male; D009206:Myocardium / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018487:Ventricular Dysfunction, Left / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D000093842:Matrines
chemical_list: D000470:Alkaloids; D002316:Cardiotonic Agents; C035933:sophocarpine; D000093842:Matrines
keywords: 9; Cardiac hypertrophy; MMP-2; NF-κB signaling pathway; collagen content; pro-inflammatory cytokine