Ligustrazine improves atherosclerosis in rat via attenuation of oxidative stress.

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 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. 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.

Ophiopogonin D prevents H2O2-induced injury in primary human umbilical vein endothelial cells.

AIM OF THE STUDY: Vessel endothelium injury caused by reactive oxygen species (ROS) including H(2)O(2) plays a critical role in the pathogenesis of cardiovascular disorders. Therefore, drug targeting ROS elimination has highly clinical values in cardiovascular therapy. The plant of Radix Ophiopogon japonicus is a traditional Chinese herbal medicine that has been commonly used for prevention and treatment of cardiovascular diseases for a long history. However, the effective component mediating its beneficial effects remains unknown. In the present study, we investigated the action of Ophiopogonin D (OP-D), one of the most bioactive components of Radix Ophiopogon japonicus, in an endothelial injury model induced by H(2)O(2). MATERIALS AND METHODS: Primarily cultured human umbilical vein endothelial cells (HUVECs) were pretreated with increased doses of OP-D overnight and then challenged with H(2)O(2). The protective effects of OP-D against H(2)O(2) were evaluated. RESULTS: We found that OP-D inhibited mRNA levels of antioxidant, inflammatory and apoptotic genes in a dose-dependent manner in HUVECs. H(2)O(2)-induced lipid peroxidation and protein carbonylation were reduced by OP-D pretreatment. Mitochondrial ROS generation and cell apoptosis were also attenuated in OP-D pretreated cells. In addition, OP-D restored cellular total antioxidative capacity and inhibited the release of inflammatory cytokines. Furthermore, OP-D suppressed the enzymatic activity of catalase, HO-1, and caspases. Finally, OP-D blocked activation of NF-kappaB and ERK signaling cascades. CONCLUSION: Our findings provide the first evidence that OP-D plays a protective role as an effective antioxidant in H(2)O(2)-induced endothelial injury. Ophiopogonin D can be therefore developed as a novel drug for the therapy of cardiovascular disorders.