RESUMO
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.
Assuntos
Anticolesterolemiantes/farmacologia , Capsaicina/farmacologia , Colesterol na Dieta/administração & dosagem , Animais , Ácidos e Sais Biliares/metabolismo , Colesterol/metabolismo , Colesterol 7-alfa-Hidroxilase/genética , Colesterol 7-alfa-Hidroxilase/metabolismo , Regulação para Baixo , Fezes/química , Feminino , Hidroximetilglutaril-CoA Redutases/genética , Hidroximetilglutaril-CoA Redutases/metabolismo , Íleo/efeitos dos fármacos , Íleo/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Transportadores de Ânions Orgânicos Dependentes de Sódio/genética , Transportadores de Ânions Orgânicos Dependentes de Sódio/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley , Simportadores/genética , Simportadores/metabolismo , Canais de Cátion TRPV/genética , Canais de Cátion TRPV/metabolismo , Regulação para CimaRESUMO
SCOPE: This study investigated the interaction of dietary capsaicinoids with the mRNA and protein expressions of key receptors and enzymes involved in cholesterol metabolism in ovariectomized (OVX) rats. METHODS AND RESULTS: Female Sprague-Dawley rats were subjected to sham operation or ovariectomy. The sham group and OVX control group were fed with high-cholesterol diets, whereas the treatment group (control diet containing 0.01% capsaicinoids) was fed with high-cholesterol plus 0.01% capsaicinoids diet for 21 days. Capsaicinoids significantly decreased the body weight gain, plasma total cholesterol, LDL cholesterol, and triacylglycerol without affecting the high-density lipoprotein cholesterol in the OVX rats. The change in plasma lipoprotein profile was accompanied by a greater excretion of total bile acid in feces and small intestinal contents. Western blot and real-time PCR analyses revealed that capsaicinoids significantly enhanced the expressions of hepatic cholesterol 7α-hydroxylase and transient receptor potential vanilloid type-1 but did not affect the expression of 3-hydroxy-3-methylglutaryl-CoA reductase in the OVX rats. CONCLUSION: 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.
Assuntos
Anticolesterolemiantes/farmacologia , Ácidos e Sais Biliares/metabolismo , Capsaicina/análogos & derivados , Capsaicina/farmacologia , Animais , Colesterol/sangue , Colesterol/metabolismo , Colesterol 7-alfa-Hidroxilase/metabolismo , HDL-Colesterol/metabolismo , LDL-Colesterol/metabolismo , Ingestão de Alimentos/efeitos dos fármacos , Feminino , Intestino Delgado/efeitos dos fármacos , Intestino Delgado/metabolismo , Lipídeos/sangue , Fígado/efeitos dos fármacos , Transportadores de Ânions Orgânicos Dependentes de Sódio/metabolismo , Ovariectomia/efeitos adversos , Ratos , Ratos Sprague-Dawley , Simportadores/metabolismo , Triglicerídeos/metabolismo , Aumento de Peso/efeitos dos fármacosRESUMO
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.
