Current work was conducted to evaluate the safety and antihypercholesterolemic activity of jatrorrhizine extracted from Rhizoma Coptidis (RC) and its potential mechanism on regulating cholesterol metabolism. It was found that the LD50 of jatrorrhizine in mice was more than 5,500 mg/kg and there were no influences on clinical signs, organ weight changes, urinalysis and hematological parameters, gross necropsy and histological alterations in jatrorrhizine-treated rats during the 3-month period, compared to the control group. Jatrorrhizine showed a strong lipid-lowering effect in a dose-dependent manner. Oral administration of 70.05 mg/kg of jatrorrhizine on Mesocricetus auratus (Syrian golden hamsters) exhibited significant decrease in TC, TG, and LDL-c levels by 20%, 43%, and 19%, respectively, and increase in HDL-c and total bile acids (TBA) content in feces (p<0.01), compared to high-fat and high-cholesterol (HFHC) group. Besides, jatrorrhizine dose-dependently slowed the rate of weight gain. The results of qRT-PCR, western blotting and ELISA revealed that jatrorrhizine significantly up-regulated the mRNA and protein expression of LDLR and CYP7A1, but exhibited no significant effect on mRNA and protein expression of HMGR and ASBT in hamsters. In conclusion, jatrorrhizine was a safe and potential antihypercholesterolemic agent from RC which could improve the utilization and excretion of cholesterol by up-regulating the mRNA and protein expression of LDLR and CYP7A1.
Keywords: Antihypercholesterolemia; CYP7A1; Jatrorrhizine; LDLR; Rhizoma Coptidis.
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