Capsaicinoids have cholesterol-lowering effects in OVX rats. The hypocholesterolemic activity of capsaicinoids is caused by the stimulating conversion of cholesterol to bile acids by upregulation of cholesterol 7α-hydroxylase expression and the increase in fecal total bile acid excretion.

The potential mechanism of the hypocholesterolemic effect of capsaicinoids in rats fed with cholesterol-enriched and cholesterol-free diets was determined. Capsaicinoids favorably modified the lipoprotein profile of rats. Capsaicinoids consumption down-regulated the mRNA levels of hepatic 3-hydroxyl-3-methylglutaryl CoA (HMG-CoA) reductase by 0.55-fold and hepatic cholesterol-7α-hydroxylase (CYP7A1) by 0.53-fold in the cholesterol-free diet group (P < 0.05) but up-regulated the CYP7A1 level by 1.38-fold in the cholesterol-enriched diet group (P < 0.05). It also increased the expression levels of ileal bile acid binding protein and apical sodium-dependent bile acid transporter in the ileum, as well as transient receptor potential vanilloid type-1 in the liver and ileum in the different groups. Capsaicinoids reduced the amount of bile acids in feces by -15.97% and contents of the small intestine by -9.64% in the cholesterol-free diet group (P < 0.05) but increased both by 13.06% and 10.20%, respectively, in the cholesterol-enriched diet group. The cholesterol-lowering action of capsaicinoids in the cholesterol-free diet group was attributed to the inhibition of hepatic cholesterol synthesis, whereas that in the cholesterol-enriched diet group was attributed to the stimulation of the conversion of cholesterol to bile acids and the increasing excretions of bile acids in feces.

Previous studies showed that capsaicinoid supplementation favorably modifies the plasma lipoprotein profile. The present study investigated the effect of capsaicinoids on plasma lipids and gene expressions of key receptors and enzymes involved in cholesterol metabolism in ovariectomized (OVX) rats. OVX rats were fed with a cholesterol-free diet and orally administered 0 mg kg(-1) bw (OVX-CON), 5 mg kg(-1) bw (OVX-LD), 10 mg kg(-1) bw (OVX-MD), and 15 mg kg(-1) bw (OVX-HD) capsaicinoids daily for 28 days. As the capsaicinoids dose increased, body weight gain and concentrations of plasma triglyceride, total cholesterol, and low-density lipoprotein cholesterol, as well as total lipid accumulation were significantly decreased. In addition, the mRNA levels of hepatic 3-hydroxyl-3-methylglutaryl CoA reductase and cholesterol-7α-hydroxylase were down-regulated, whereas those of transient receptor potential vanilloid type-1, ileal apical sodium-dependent bile acid transporter, and intestinal bile acid binding protein were up-regulated. The excretion of small intestinal bile acid contents and fecal bile acid also decreased. These results suggest that capsaicinoids can prevent ovarian hormone deficiency-induced hypercholesterolemia by inhibiting the hepatic cholesterol synthesis.

Sex differences on the effect of dose-dependent capsaicinoids on lipid metabolism were studied in rats. 24 rats of each sex were administered orally 0 mg/kg, 2.5 mg/kg, 5 mg/kg or 7.5 mg/kg capsaicinoids daily for 28 days. In male rats, body weight gained, and the levels of total lipids, total cholesterol and triglycerides in the liver were significantly decreased as the dose of capsaicinoids increased. On the other hand, plasma total cholesterol (TC), triglycerides (TG), HDL- and LDL-cholesterol concentration and liver weight were not affected by capsaicinoids. While in female rats, plasma TC, TG, HDL-C and LDL-C concentration, liver total lipids, TC and TG concentration were significantly decreased as the dose of capsaicinoids increased. The mRNA level of hepatic TRPV1, ileac ASBT and IBABP were increased as the dose of capsaicinoids increased in all rats groups. The mRNA level of hepatic HMG-CoA reductase, CYP7A1 and FXR were significantly decreased in female rats groups. These results show that the hypocholesterolemic effect of capsaicinoids in dose-dependent manner in rats was mediated by inhibited synthesis of endogenous cholesterol, female rats were more sensitive than male rats on hypolipidemic effect of capsaicinoids.