title: Ligustrazine improves atherosclerosis in rat via attenuation of oxidative stress.
abstract: BACKGROUND
  Ligustrazine (Lig) is a compound isolated from the rhizome of Ligusticum chuanxiong Hort. (Umbelliferae) and has been reported to be effective for the treatment of a variety of vascular diseases.
  
  
  OBJECTIVE
  The anti-atherosclerotic activities of Lig are evaluated in vivo for the first time in the present study.
  
  
  METHODS
  We gave rats a single injection of vitamin D3 and then fed them with an atherogenic diet for 6 weeks to induce atherosclerosis. Lig was simultaneously given to rats by gavage at the dose of 20 or 80 mg/kg in the therapy groups. Multiple approaches including spectrophotometry, hematoxylin and eosin (H&E) staining, and quantitative RT-PCR were applied to investigate the effects of Lig on blood parameters, aorta and liver histology, and gene expression. In addition, the solely effects of Lig on food intake, body weight gain, and taste preference were also evaluated.
  
  
  RESULTS
  We found that two doses of Lig treatment decreased the total cholesterol levels by 65.2 and 76.7%, respectively, in the plasma. Triglyceride (by 53.2 and 77.9%) and low-density lipoprotein (by 71.2 and 79.0%) levels were also decreased. However, high-density lipoprotein level was slightly increased. The circulating endothelial cells were decreased by 42.2 and 60.0% in Lig-treated rats, indicating the attenuation of endothelial injury. In contrast, Lig restored the total antioxidant capacity and superoxide dismutase 1 (SOD1) activity while decreasing the MDA generation. Furthermore, Lig improved liver dysfunction by decreasing ALT (by 13.0 and 49.7%) and AST (by 10.7 and 14.3%) levels. Histological examinations revealed that Lig suppressed atherosclerotic plaque progression in the thoracic aorta and lipid accumulation in the liver. At the transcriptional level, Lig inhibited the induction of antioxidant genes both in aorta and in liver. Lig also suppressed the mRNA expression of the genes involved in the hepatic fatty acid oxidation. Finally, Lig had a minimum effect on food intake, body weight gain, and taste preference.
  
  
  CONCLUSIONS
  Our results suggest that Lig suppresses the development of atherosclerosis and hepatic lipid accumulation via the alleviation of oxidative stress and the improvement of dyslipidemia.
authors.affiliation: Jiangsu Key Laboratory for Molecular and Medical Biotechnology, Nanjing Normal University, Nanjing, China.
authors.forename: Fengrong
authors.initials: F
authors.lastname: Jiang
authors.forename: Jinchun
authors.initials: J
authors.lastname: Qian
authors.forename: Siyu
authors.initials: S
authors.lastname: Chen
authors.forename: Wenbo
authors.initials: W
authors.lastname: Zhang
authors.forename: Chang
authors.initials: C
authors.lastname: Liu
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology* / Q000627:therapeutic use; D001013:Aorta, Thoracic / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D050197:Atherosclerosis / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D002784:Cholesterol / Q000097:blood; D004036:Diet, Atherogenic; D004305:Dose-Response Relationship, Drug; D004365:Drugs, Chinese Herbal; D050171:Dyslipidemias / Q000188:drug therapy / Q000378:metabolism; D030004:Ligusticum; D050356:Lipid Metabolism / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008111:Liver Function Tests; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects*; D008517:Phytotherapy; D011719:Pyrazines / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D027343:Rhizome; D014280:Triglycerides / Q000097:blood; D014665:Vasodilator Agents / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D000975:Antioxidants; D004365:Drugs, Chinese Herbal; D011719:Pyrazines; D014280:Triglycerides; D014665:Vasodilator Agents; D002784:Cholesterol; C101574:chuangxiong extract; C017953:tetramethylpyrazine