Effects Of Alfalfa Saponins On Rat Cholesterol Metabolism And Its Regulation Mechanism

The experiments were conducted to investigate the effects of alfalfa saponins oncholesterol metabolism and its molecular mechanism, SD rats、BRL cell and ANA-1cellwere used as material，the effects of alfalfa saponin on cholesterol metabolism were studiedon animal level and its regulation mechanism was studied on cell and molecular level，thedetails are as follows：Exp.1: Effects of alfalfa saponins on cholesterol metabolism of rats.32healthy male SD rats were randomly divided into four groups: normol control Group,alfalfa saponins group, hyperlipidemia model Group, hyperlipidemia model+alfalfa saponinsgroup. The first four weeks were hyperlipidemia model estabilishing period, the rats in thenormal control group and alfala saponin group were fed with a basal diet; the other twogroups were fed with high fat diet; the last four weeks were alfalfa saponins treatmentperiod, alfalfa saponins (240mg/kg) were administrated to alfalfa saponin group andhyperlipidemia model+alfalfa saponins group by gavage. The body weight, liver index,serum lipid level, total cholesterol and total bile acids in liver and feces of rats weredetermined. The results showed that: Alfalfa saponins significantly decreased body weight,liver index and serum cholesterol level, increased accumulation of cholesterol in liver andexcretion of cholesterol and bile acids in feces in hyperlipidemia rats; significantly increasedcholesterol excretion in feces in normal rats. The results indicated that alfalfa sapinins couldadjust the distribution of cholesterol in rats and had a significant effect on the decrease ofserum lipid.Exp.2: Study on molecular mechanism of alfalfa saponin on cholesterolmetabolism.The mRNA expressions of some genes related to cholesterol metabolism, secretion andtransportation were detected. In order to exclude the influence of environment andcompensatory regulation of animal body, BRL cell was cultured. Meanwhile, to investigatethe effects of alfalfa saponin on reverse cholesterol transport (RCT), foam cell model fromANA-1cell line was established，the mRNA expressions of ABCA1and SR-B1weredetected. The results showed that:(1) alfalfa saponins significantly increased the mRNAexpression of LDLR, ABCG5/ABCG8and SR-B1in normal rat liver, hence incresed cholesterol secretion and transportation.(2) alfalfa saponins significantly increased themRNA expressions of LDLR, ABCA1, ABCG5/ABCG8and CYP7A1in liver ofhyperlipidemia rats，as a result, increased transportation of cholesterol, excretion of neutralcholesterol and generation of bile acids.(3) alfalfa saponins significantly increased themRNA expressions of LDLR, ABCA1andABCG5/ABCG8in normal BRL cell，which wasthe same with the results of normal rats. Alfalfa saponins had no effects on hyperlipidemicBRL cell, which was not consistent with the results of hyperlipidemia rats.(4) alfalfasaponins had little effect on the mRNA expressions of ABCA1and SR-B1in ANA-1cell.These findings indicated that:(1) the hypocholesterolemic effects of alfalfa saponins couldbe resulted from the rise in mRNA expression of LDLR, ABCG5/ABCG8and CYP7A1.(2)alfalfa saponins significantly increased the mRNA expressions of LDLR and CYP7A1inhyperlipidemia rats，but had little effect in BRL cell，which suggested the effects of alfalfasaponins on mRNA expressions of LDLR and CYP7A1in hyperlipidemia rats maybe notdirect.(3) alfalfa saponins had little effect on cholesterol reverse transport in macrophage,and mainly affected cholesterol reverse transport in liver.