Effect Of8-alkylberberine Derivatives On Antihyperlipidemia And LDLR Expression In Liver

Berberine (BBR) is the main bio-active compounds in Rhizoma Coptis, exhibiting significant cholesterol-lowering activity. To investigate the antihyperlipideia effect of8-alkyl-BBR derivatives, the changes in LDLR expression and cholesterol-lowering activity were detected by using HepG2cell and hyperlipidemia mice. The results were as follows:To guarantee the good growth of HepG2cells, the effects of BBR derivatives with different carbon length and different concentration on cells proliferation by the method of MTT were measured. The results showed that80%of HepG2cells would survive when the concentration of BBR and8-alkyl-BBR derivatives reach to0.2mg/L and0.03mg/L respectively. Therefore,0.2mg/L BBR and0.03mg/L of8-alkyl-BBR derivatives were chosen as the standard concentration in subsequent experiment.Firstly, HepG2cells in good status were treated with0.2mg/L BBR and0.03mg/L of8-alkyl-BBR derivatives and of the LDLR protein expression was analyzed by western blotting. The results indicated that LDLR protein expression in all experimental groups was higher than that in the control group, and its expression was increased with the elongation of carbon chain. Among the compounds tested,8-cetyl-berberine showed the strongest activity of up-regulating LDLR protein expression.Next, the regulation of BBR derivatives with different concentration on LDLR expression were investigated based on the experimental results above. The results showed that BBR derivatives with a high concentration would better regulate the LDLR expression than that with a low concentration, inferring that LDLR protein expression has a dose-dependent relationship with BBR derivatives.Then, to detect the antihyperlipidemia activity of BBR derivatives, golden mice were fed with high-cholesterol diet to obtain hypercholesterolemia model when the TC and TG respectively reached2mmol/L and8mmol/L respectively. Subsequently, the hypercholesterolemia mice were treated with BBR and its derivatives for three months continuously. At the end of experiment, t blood of mice were taken from orbits to measure relative biochemical indexes and the liver were used to detect the effect of BBR and its derivatives on LDLR expression. Experimental results showed that the weight gain of mice in drug group were lower than that in the high fat group, the weight of mice in8-hexadecyl berberine group is closest to the normal weight group, as the liver LDLR results. TC, TG, LDL-C in drug group were declined, HDL-C increased, the ability of8-hexadecyl berberine regulating TC, TG, LDL and HDL-C is the strongest, which suggested that BBR and its derivatives, especially8-hexadecyl berberine had good effects on improving weight and relative liver weight, and lowering cholesterol in mice.