Ligustrazine improves atherosclerosis in rat via attenuation of oxidative stress
Pharmaceutical Biology (2011), 49: 856-863.，-0001，（）：
Context: 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. Materials and 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 spectrophometry, hematoxylin and eosin 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 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. Discussion and conclusion: 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.