title: Effect of berberine on PPARα-NO signalling pathway in vascular smooth muscle cell proliferation induced by angiotensin IV.
abstract: BACKGROUND
  The available treatments for the abnormal proliferation of vascular smooth muscle cells (VSMCs) are still dismal. Berberine has been demonstrated to possess extensive medicine activity, yet relatively little is known about its effect on VSMCs proliferation. Many studies showed that PPARα and NO participated in the process of VSMCs proliferation.
  
  
  OBJECTIVE
  To evaluate the effect of berberine and its possible influence on PPARα-NO pathway in angiotensin IV-stimulated VSMCs.
  
  
  METHODS
  The primary VSMCs were cultured with the tissue explants method, and the proliferation was characterized by MTT and protein content. Protein and mRNA expression were measured by Western blot and real-time RT-PCR, respectively. NO synthase (NOS) activity was measured using a spectrophotometric assay, and NO concentration was measured using the Griess assay.
  
  
  RESULTS
  Angiotensin IV (0.1 nmol/L)-induced VSMCs proliferation was evidenced by increasing the optical density at A490and total protein content (p < 0.01), which was inhibited by berberine (10, 30 and 100 μmol/L) in a concentration-dependent manner (p < 0.05). Angiotensin IV decreased the expression of PPARα at mRNA and protein level (p < 0.05), which occurred in parallel with declining eNOS mRNA expression, NOS activity and NO concentration (p < 0.01). Berberine at 30 μmol/L reversed the effects of angiotensin IV in VSMCs (p < 0.05), which were abolished by MK 886 (0.3 μmol/L) (p < 0.05).
  
  
  CONCLUSIONS
  The results support the therapeutic effects of berberine on angiotensin IV-induced proliferation in cultured VSMCs at least partially through targeting the PPARα-NO signalling pathway.
authors.affiliation: a Department of Pharmacology, Chongqing Key Laboratory of Biochemistry and Molecular Pharmacology , Chongqing Medical University , Chongqing , P.R. China.
authors.forename: Hongmei
authors.initials: H
authors.lastname: Qiu
authors.affiliation: a Department of Pharmacology, Chongqing Key Laboratory of Biochemistry and Molecular Pharmacology , Chongqing Medical University , Chongqing , P.R. China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Wu
authors.affiliation: a Department of Pharmacology, Chongqing Key Laboratory of Biochemistry and Molecular Pharmacology , Chongqing Medical University , Chongqing , P.R. China.
authors.forename: Quanhua
authors.initials: Q
authors.lastname: Wang
authors.affiliation: a Department of Pharmacology, Chongqing Key Laboratory of Biochemistry and Molecular Pharmacology , Chongqing Medical University , Chongqing , P.R. China.
authors.forename: Changqing
authors.initials: C
authors.lastname: Liu
authors.affiliation: a Department of Pharmacology, Chongqing Key Laboratory of Biochemistry and Molecular Pharmacology , Chongqing Medical University , Chongqing , P.R. China.
authors.forename: Lai
authors.initials: L
authors.lastname: Xue
authors.affiliation: a Department of Pharmacology, Chongqing Key Laboratory of Biochemistry and Molecular Pharmacology , Chongqing Medical University , Chongqing , P.R. China.
authors.forename: Hong
authors.initials: H
authors.lastname: Wang
authors.affiliation: b Department of Pharmacology, Key Laboratory for Basic Pharmacology of Ministry of Education , Zunyi Medical College , Guizhou , P.R. China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Wu
authors.affiliation: a Department of Pharmacology, Chongqing Key Laboratory of Biochemistry and Molecular Pharmacology , Chongqing Medical University , Chongqing , P.R. China.
authors.forename: Qingsong
authors.initials: Q
authors.lastname: Jiang
mesh_terms: D000804:Angiotensin II / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D001599:Berberine / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005260:Female; D007211:Indoles / Q000494:pharmacology; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000187:drug effects* / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D052250:Nitric Oxide Synthase Type III / Q000235:genetics / Q000378:metabolism; D047493:PPAR alpha / Q000819:agonists* / Q000235:genetics / Q000378:metabolism; D061251:Primary Cell Culture; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects*; D002722:Chlorobenzenes
chemical_list: D000804:Angiotensin II; D001599:Berberine; D007211:Indoles; D009569:Nitric Oxide; D052250:Nitric Oxide Synthase Type III; D047493:PPAR alpha; D012333:RNA, Messenger; C060893:MK-886; D002722:Chlorobenzenes; C012877:angiotensin II, des-Asp(1)-des-Arg(2)-Ile(5)-; C496316:Nos3 protein, rat
keywords: NOS; Peroxisome proliferator-activated receptor-α; eNOSl