Antihyperlipidemic Effect And Mechanisms Of Jatrorrhizine From Rhizoma Coptidis On HepG2Cell And Syrian Golden Hamsters

With the improvement of living standards and the changes in human dietary habits, the incidence of hyperlipidemia is increased by years. Hyperlipidemia, actually higher concentrations of TC, TG and LDL-c and lower concentrations of functional HDL-c, is a metabolic disorder that constitutes a crucial risk factor of increased cardiovascular morbidity and mortality. It is widely acknowledged that controlling the level of total cholesterol (TC) can interfere with the progression of atherosclerosis and reduce cardiovascular events. Now medical evidences showed that Rhizoma Coptidis (RC) had antibacterial, antiviral, anti-inflammatory, antihyperglycemic and hypolipidemic effects. Jatrorrhizine, a quaternary protoberberine alkaloid (QPA), is one of the main active ingredients in RC. In this study, the antihyperlipidemic effect and mechanism of jatrorrhizine on HepG2cell and Syrian golden hamsters are evaluated.The following is the main contents and results of this project:(1) Effect and potential mechanisms of alkaloids from Rhizoma Coptidis on antihyperlipidemia in HepG2cells. The results showed that alkaloids from Rhizoma Coptidis influenced the mRNA and protein expression of HMGR, LDLR, CYP7A1and ASBT.(2) Jatrorrhizine with a purity of98.5%was successfully isolated and purified from RC. (3) According to the evaluation on the acute and sub-chronic toxicity, jatrorrhizine showed a very high LD50value which was about5500mg/kg and there were no significant differences in clinical signs, organ weight changes, urinalysis and hematological parameters in jatrorrhizine-treated animals compared to the control group during the90-day period. The result showed that the jatrorrhizine is safe compound (2).(4) Based on the data from Syrian golden hamsters, HFHC diet induced a rapid increase in body weight and serum TC, TG and LDL-c levels and a slight reduce in HDL-c. However, orally administration for4weeks, jatrorrhizine showed a strong lipid-lowering effect in a dose-dependent manner and recovered the body weight. Especially, at the dosage of70.05mg/kg, jatrorrhizine can be improved the body weight, and significantly lowered TC, TG, and LDL-c levels by20%,43%, and19%, respectively, and increased HDL-c by25%(P<0.01), compared to HFHC group. Besides, jatrorrhizine treatment significantly reduced the level of total bile acids and raised the total bile acids (TBA) content in feces of hamsters, which was higher than that of BBR treatment with the same dosage.(5) The mRNA expression and protein level of genes involved in cholesterol metabolism were analyzed by RT-qPCR, western blotting and ELISA. The results have revealed that jatrorrhizine could significantly increase mRNA and protein expression of LDLR and CYP7A1:at a dose of70.05mg/kg, jatrorrhizine increased mRNA and protein level of LDLR by4-fold and27%respectively, compared to HFHC group.In conclusion, jatrorrhizine was a potential safe anti-hypercholesterolemic agent from RC which could improve the utilization and excretion of cholesterol by up-regulating the mRNA and protein expression of LDLR and CYP7A1.