RESUMEN
We observed the variation in in vivo blood lipid and blood glucose metabolism in rats with atherosclerosis after 5-(3,4-dihydroxy-phenyl)-1-piperidin-1-yl-penta-2,4-dien-1-one (GBOT) administration. Wistar rats aged 10 weeks received a high-fat diet to establish the atherosclerosis model. Metabolic indices related to blood lipid and blood glucose were measured before modeling and at 4 and 8 weeks after modeling. Liver fat levels in rats were measured at 8 weeks to analyze the relationship between liver fat and blood lipid levels. We examined the mechanism of blood lipid reduction. The levels of serum triglycerides, total cholesterol, and very-low-density lipoprotein cholesterol in rats in the control group were significantly decreased (P < 0.05) compared with those in the 4-week control group at 4 weeks and decreased significantly and continuously until the 8th week (P < 0.05). Compared with the 8-week control group, the blood glucose level in rats in the 8-week experimental group decreased significantly (P < 0.05), and the level of insulin sensitivity index decreased significantly (P < 0.05). Compared with the control group, triglyceride and total cholesterol levels per unit mass in rat liver tissue in the 8-week experimental group decreased significantly (P < 0.05). Western blotting indicated that GBOT significantly increased the expression of lecithin-cholesterol acyltransferase, low-density lipoprotein receptor, and cholesterol 7 alpha-hydroxylase proteins. GBOT can significantly decrease the levels of blood lipid and blood glucose in rat models of atherosclerosis, and its mechanism may be associated with the promotion of expression of lecithin-cholesterol acyltransferase, low-density lipoprotein receptor, and cholesterol 7 alpha-hydroxylase proteins.
Asunto(s)
Aterosclerosis/sangre , Aterosclerosis/metabolismo , Glucemia/metabolismo , Lípidos/sangre , Piperidinas/farmacología , Alcamidas Poliinsaturadas/farmacología , Animales , Aorta/efectos de los fármacos , Aorta/patología , Hidrocarburo de Aril Hidroxilasas/metabolismo , Western Blotting , Peso Corporal/efectos de los fármacos , Colesterol/sangre , Insulina/sangre , Masculino , Fosfatidilcolina-Esterol O-Aciltransferasa/metabolismo , Piperidinas/química , Alcamidas Poliinsaturadas/química , Ratas Wistar , Receptores de LDL/metabolismo , Esteroide Hidroxilasas/metabolismo , Triglicéridos/sangreRESUMEN
A novel thermostable form of piperlonguminine (GB-N) was extracted from medicinal plant Piper longum in efforts to explore the bioactive components underlying the mechanism of Piper longum in reducing plasma lipids. In vitro, HepG2 cells were employed to investigate the effects of GB-N on regulating cellular total cholesterol and low-density lipoprotein (LDL) receptor (LDLR) mRNA abundance, while high-fat and high-cholesterol diet-induced hyperlipidemic Wistar rats were used to investigate in vivo effects of GB-N. Cellular total cholesterol assay showed that GB-N dose-dependently reduced cellular total cholesterol in HepG2 cells in the presence and absence of elevated plasma cholesterol levels by 25% and 32%, respectively. Reverse transcription PCR assay showed that LDLR mRNA abundance was up-regulated dose-dependently by 142% via GB-N treatment in HepG2 cells. Animal experiment revealed that GB-N dose-dependently reduced serum total cholesterol by 26%, triglyceride by 47%, LDL cholesterol by 30%, while increased serum high-density lipoprotein (HDL) cholesterol by 524% in diet-induced hyperlipidemic Wistar rats. In conclusion, the results suggest the potential therapeutic uses of GB-N in the prevention and treatment of hyperlipidemia and related diseases.