Astragalus polysaccharides lowers plasma cholesterol through mechanisms distinct from statins

Abstract

To determine the efficacy and underlying mechanism of Astragalus polysaccharides (APS) on plasma lipids in hypercholesterolemia hamsters. The effect of APS (0.25 g/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.

Figure 1. Changes of plasma lipids in response to APS and simvastatin treatments.

APS and simvastatin significantly lowered total cholesterol (TC), triglycerides (TG), high-density lipoprotein –cholesterol (HDL-C) and low-density lipoprotein-cholesterol (LDL-C) concentrations compared to the control. # P<0.05 compared with control group.

Figure 2. Relationships between plasma lipids and intestinal cholesterol absorption.

Intestinal cholesterol absorption rates are significantly correlated with the plasma LDL-C (A) and TC (B) levels, respectively.

Figure 3. Cholesterol metabolism associated gene and protein expressions.

Representative Western blot and group data depicting LDLR protein and mRNA abundance (A), cyp7α-1 protein and mRNA abundance (B) in livers, ABCG5 protein and mRNA abundance(C), ABCG8 protein and mRNA abundance(D), NPC1L1 protein and mRNA abundance(E) in intestines of hamsters. N = 8 per group. # P<0.05 compared with Control group, *P<0.05 compared with Simvastatin group.

Figure 4. HE staining of liver tissue from different groups (Original magnification, ×200).

A: control group; B: APS group; C: Simvastatin group. Livers of APS and Simvastatin group show mild fatty degeneration. In contrast, livers of control rats showed severe fatty degeneration, extensive hepatocytes hypertrophy, oedema, and vacuolization of the hepatocyte cytoplasm.