Suppression of Diet-Induced Hypercholesterolemia by Scutellarin in Rats

Abstract

Hypercholesterolemia is a major risk factor for the development and progression of cardiovascular diseases including atherosclerosis. A major active ingredient scutellarin, from the plant Erigeron breviscapus was investigated for its hypocholesterolemic and atheroscleroprotective effects (30 and 100 mg/kg/day, p.o.). The serum lipid profile (total cholesterol, triglycerides, high density lipoprotein cholesterol and low density lipoprotein cholesterol) was monitored and aortic functions in Sprague-Dawley rats fed with normal diet, atherogenic diet or atherogenic diet plus oral administration of either scutellarin or simvastatin (a positive control) were tested. It was found that scutellarin markedly attenuated the increased serum total cholesterol induced by atherogenic diet. It caused a significant reduction in the atherogenic index. In addition, scutellarin administration could significantly enhance acetylcholine-induced nitrate/nitrite production, increase the gene expression of endothelial nitric oxide synthase and improve acetylcholine-induced endothelium-dependent vasorelaxation in rat isolated aortas. These data revealed that scutellarin could reduce the atherogenic properties of dietary cholesterol in rats. However, whether scutellarin's atheroscleroprotective potential targets endothelial function directly or indirectly on its antioxidative activity remains to be determined.

Breviscapine inhibits high glucose-induced proliferation and migration of cultured vascular smooth muscle cells of rats via suppressing the ERK1/2 MAPK signaling pathway

“…In a recent report, breviscapine inhibited the proliferation and collagen production of cardiac fibroblasts that is induced by angiotensin II, as well as angiotensin II-induced phosphorylation of p38 and ERK1/2 MAPK [19] . Because the ERK1/2 MAPK pathway was activated in response to hyperglycemia and was involved in the high glucose-induced proliferation and migration of VSMCs, we tried to establish whether the MAPK pathway plays a role in the protective effect of breviscapine against VSMC functional impairment under high glucose conditions.…”

“…However, little is known about whether breviscapine has a protective role in diabetic atherosclerosis, which is a common complication of diabetes mellitus that is independent of diabetic cardiomyopathy. A previous study demonstrated that breviscapine potentially had a protective effect on atherosclerosis and caused a significant reduction in the atherogenic index in rat atherosclerotic models [19] . However, whether breviscapine's anti-atherogenic effect resolves the functional impairments of VSMCs remains to be determined.…”

“…Other studies have demonstrated that breviscapine inhibited the proliferation and collagen production by cardiac fibroblasts that were induced by angiotensin II through the suppression of the p38 and ERK1/2 MAPK signaling pathways [18] . In addition, breviscapine has been shown to potentially have a protective effect against atherosclerosis in rats [19] . Despite a preponderance of data, little is known about the underlying mechanisms of breviscapine.…”

Effect of Blepharis maderaspatensis L. Roth. extracts on serum lipids in Triton WR-1339 and high cholesterol diet induced hyperlipidemia in rats

“…Group 1 (control) was fed with normal rat chow, which was obtained from Lipton India Ltd [composition: protein (~14%), fat (~10%) and carbohydrate (~76%)]. Other groups of animals were fed with hypercholesterolemic diet (HCD) contained normal rat chow with the supplement of cholic acid (1%), cholesterol (2%) and cooking oil (5.5%) as described elsewhere (Yan et al, 2006;Li et al, 2009). Group 2 (model control) rats were treated orally with 10 ml/kg of 0.5% methylcellulose (w/v) in distilled water.…”

Metabolic and pharmacokinetic studies of scutellarin in rat plasma, urine, and feces

“…Scutellarin has been extensively used for the clinical treatment of cardiovascular and cerebrovascular diseases in China for many years. Pharmacological research indicates that scutellarin is associated with antihypertrophic effects [1] , fibrinolysis and anticoagulant effects [2] , protective effects in the brain and heart [3] , hypercholesterolemia suppression [4] , and endothelium-independent relaxation induction [5] . Scutellarin produces an anti-inflammatory effect via actions on arachidonic acid metabolism [6] .…”