Abstract
To determine the efficacy and underlying mechanism of Astragalus polysaccharides (APS) on plasma lipids in hypercholesterolemia hamsters. The effect of APS (0.25g/kg/d) on plasma and liver lipids, fecal bile acids and neutral sterol, cholesterol absorption and synthesis, HMG-CoA reductase activity, and gene and protein expressions in the liver and small intestine was investigated in twenty-four hypercholesterolemia hamsters. Treatment periods lasted for three months. APS significantly lowered plasma total cholesterol by 45.8%, triglycerides by 30%, and low-density lipoprotein-cholesterol by 47.4%, comparable to simvastatin. Further examinations revealed that APS reduced total cholesterol and triglycerides in the liver, increased fecal bile acid and neutral sterol excretion, inhibited cholesterol absorption, and by contrast, increased hepatic cholesterol synthesis and HMG-CoA reductase activity. Plasma total cholesterol or low-density lipoprotein-cholesterol levels were significantly correlated with cholesterol absorption rates. APS up-regulated cholesterol-7α-hydroxylase and LDL-receptor gene expressions. These new findings identify APS as a potential natural cholesterol lowering agent, working through mechanisms distinct from statins.
Highlights
Hypercholesterolemia is a contributing factor to atherosclerosis and consequent cardiovascular and cerebrovascular disease
Effect of Astragalus polysaccharides (APS) on plasma lipoproteins Before APS treatment, animals were fed a high fat diet for three months, which significantly increased plasma total cholesterol (TC), TG, low-density lipoprotein-cholesterol (LDL-C) and high-density lipoprotein-cholesterol (HDL-C) and no intergroup differences were found (P.0.05). Treatments of these hyperlipidemic animals with APS and simvastatin for three months resulted in marked decreases in plasma TC, TG, and LDL-C concentrations
The difference failed to achieve statistical significance between APS and Simvastatin group. Both APS and simvastatin reduced (p,0.05) plasma HDL-C levels compared to the control group (Figure 1)
Summary
Hypercholesterolemia is a contributing factor to atherosclerosis and consequent cardiovascular and cerebrovascular disease. Statins effectively lower plasma cholesterol by inhibiting HMG-CoA reductase activity [1]. It is desirable to develop natural drugs that have cholesterol-lowering effect comparable to statins, but could be tolerated well by the patients. APS-I and APSII are well known to be the major structural components of APS. APS-I (molecular weight = 1,699,100 Da) consists of arabinose and glucose in a molar ratio of 1:3.45, while APS-II (molecular weight = 1,197,600 Da) consists of rhamnose, arabinose and glucose in a molar ratio of 1:6.25:17.86 [3]. In China, APS has been extensively used to treat viral infection [4,5], acute myocarditis [6], glomerulonephritis [7], diabetes [8], tumor [9], and many other illnesses, with no toxic record in clinic
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