Effects Of Berberine On The Hypercholesterolemiamay Involve In The Insig-2 Gene Expression In Liver

Objective:To investigate the effects of berberine (Ber) on cholesterol metabolism and its mechanism。Methods:1. SD rats were randomly divided into 5 groups: normal diet + pretreatment of solvent (ND); high-fat and high-cholesterol diet + pretreatment of solvent (HFD); high-fat and high-cholesterol diet + pretreatments of either lovastatin(LD) orBer low dose (BLD) and Ber high dose (BHD). The levels of total cholesterol(TC),low density lipoprotein cholesterol (LDL-C) , and high density lipoprotein cholesterol(HDL-C) in blood were detected eighteen weeks after rats were fed with high-fat and high-cholesterol diet and and pretreated with either solvent or drugs. The mRNA and protein expressions of Insulin-induced gene 2(Insig-2) in rat liver were quantified by RT-PCR and Western blot。2. HepG2 cells were incubated with Ber at different concentrations (1, 3, 10, 30, 100μmol/L), or incubated with 3μmol/L Ber for various times (0, 12, 24, 48, 72 h). The gene expressions of Insig-2 and VDR from HepG2 cells treated by Ber were quantified by RT-PCR and Western blot.Results:1. The blood levels of TC and LDL-C were significantly lower in Ber groups than those in HFD, except HDL-C level that was shown to clearly increase after rats were pretreatment with Ber.2.Low dose Ber pretreatment significantly increased Insig-2 gene mRNA and protein expressions from rat liver but high dose Ber pretreatment had no significantly effects on Insig-2 gene expression.3.24 h after exposure to gradient concentrations of Ber, the gene expressions of Insig-2 and VDR in HepG2 cells showed a dualistic changes:the maximum values occurred at 3μmol/L, then the values declined gradually. The pretreatment with 3μmol/L Ber for different time made the gene expressions of Insig-2 and VDR significantly increased with the peak value at 48 h;the relative coefficient between them was 0.922 (p<0.01).Conclusion:Ber can significantly decrease the levels of hyperlidemia, the mechanism of which may be related to elevating expressions of Insig-2 and VDR genes in liver. As a result the cholesterol synthesis of liver was inhibited.