Abstract
Background and aimPolysaccharide from fuzi (FPS), a Chinese herbal medicine extract, has been demonstrated to exert lipid lowering affects. In this study we examined potential mechanisms underlying this affect, specifically alterations in expression of the LDL-receptor (LDL-R), 3-hydroxy-3-methyl glutaryl (HMG)-CoA reductase and cytochrome P450 7α-1 (CYP7α-1), using a rat model of hypercholesterolemia.Methods and resultsMale rats were fed either a normal or high cholesterol (HC) diet for two-weeks. Half of the rats on the HC diet were orally gavaged with FPS (224 mg/kg, 448 mg/kg or 896 mg/kg diet) daily. Serum lipid levels were quantified at end of the study period as were liver levels of LDL-R protein and mRNA expression of CYP7α-1 and HMG-CoA. Serum cholesterol and LDL-C concentrations were significantly elevated from control in HC rats, but not in those treated with FPS (P < 0.05). LDL-R expression was significantly decreased in the HC group compared to control (P < 0.05), but significantly increased in the FPS group (P < 0.05). HMG-CoA mRNA levels were significantly increased in the HC group compared both other groups (P < 0.05), while CYP7α-1 expression was significantly higher in the FPS group compared to both other groups (P < 0.05).ConclusionThese findings suggest that the cholesterol lowering effect of FPS in hypercholesteremic rats is caused at least in part by increased hepatic LDL-R and CYP7α-1 expression and decreased HMG-CoA expression. Further study is needed to determine precisely where and how FPS exerts these effects. FPS offers potential as a therapeutic agent for the treatment of hypercholesterolemia.
Highlights
Hypercholesterolemia is an important risk factor for atherosclerosis and consequent cardiovascular and cerebrovascular disease
These findings suggest that the cholesterol lowering effect of FPS in hypercholesteremic rats is caused at least in part by increased hepatic lowdensity lipoprotein (LDL)-R and cytochrome P450 7a-1 (CYP7a-1) expression and decreased hydroxy-3-methyl glutaryl (HMG)-CoA expression
In the face of hypocholesterolemia, we found that treatment with FPS significantly reduced serum LDL and cholesterol concentrations, and increased mRNA expression of HMG-CoA reductase and CYP7a-1 in the liver
Summary
Hypercholesterolemia is an important risk factor for atherosclerosis and consequent cardiovascular and cerebrovascular disease. Increased circulating levels of lowdensity lipoprotein (LDL) underlie the development of atherosclerosis [1,2]. Statins have been shown to effectively lower LDL levels and reduce both mortality and morbidity associated with coronary heart disease by 30% [3]. Many Chinese herbal medicines contain polysaccharides which can exert a wide range of pharmacological same study, the cholesterol and LDL lowering effects of FPS were similar to that of fluvastatin. The triglyceride lowering effect, was increased following FPS compared to fluvastatin treatment. Polysaccharide from fuzi (FPS), a Chinese herbal medicine extract, has been demonstrated to exert lipid lowering affects. In this study we examined potential mechanisms underlying this affect, alterations in expression of the LDL-receptor (LDL-R), 3-hydroxy-3-methyl glutaryl (HMG)-CoA reductase and cytochrome P450 7a-1 (CYP7a-1), using a rat model of hypercholesterolemia
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