The Effect And Mechanism Of Niacin Combined With Curcumin On Blood Lipids In Hyperlipidemic Rats

Objective:To study the effect of niacin combined with curcumin on blood lipids in hyperlipidemic rats and its mechanism, in order to provide reasonable experimental basis for the synthesis of new compounds curcumin niacin esters and its derivatives.Methods:Based on the orthogonal design method for screening of target group and to determine the optimum ratio. One hundred and ten SD rats were randomly divided into normal control group, model group, solvent group, curcumin low-dose group [curcumin100mg/kg/d], curcumin high-dose group [curcumin200mg/kg/d], niacin low-dose group [niacin100mg/kg/d], niacin high-dose group [niacin200mg/kg/d], curcumin low-dose and niacin low-dose combined therapy group [curcumin100mg/kg/d+niacin100mg/kg/d], curcumin low-dose and niacin high-dose combined therapy group [curcumin100mg/kg/d+niacin200mg/kg/d], curcumin high-dose and niacin low-dose combined therapy group [curcumin200mg/kg/d+niacin100mg/kg/d], curcumin high-dose and niacin high-dose combined therapy group [curcumin200mg/kg/d+niacin200mg/kg/d]. Detection of serum lipids after8weeks. All the rats were killed and the liver samples were taken. Then hematoxylin-eosin staining. The expression of TNF-a and IL-6in liver were detected by immunohistochemical. The mRNA levels of SCAP, SREBP-2and LDLR were analyzed by RT-PCR. The protein levels of LDLR were analyzed by western blot.Results:Orthogonal design method for screening of target group. Comparison of rat survival, serum lipids and liver HE staining, we identify curcumin with niacin in the optimal mixture ratio is2:1. Compared to the normal control group, the content of TC and LDL in the model group was significantly higher(p<0.05or p<0.01), but TG didn’t rise. Compared with the model group, the solvent group had no effect on hyperlipidemic rats. Curcumin low-dose group or high-dose group can significantly decreased the content of TC, TG, LDL in blood(p<0.05or p<0.01), and no death in rats. Niacin low-dose group or high-dose group can decreased the content of TG, LDL in blood(p<0.05). However, a half of rats were death in the high-dose group. The combined treatment group could reduce the content of TC, TG, LDL in blood(p<0.05or p<0.01) and even rats mortality. Combined treatment can reduce the niacin toxicity. The hypolipidemic effects can be improved by combining curcumin and niacin [200mg/kg/d+100mg/kg/d], better than using these two drugs individually. The results of immunohistochemical show that the expression of TNF-a and IL-6were increased significantly in model group when compared with the normal group. Compared with the model group, curcumin group, niacin group and combination group were decreased significantly, which the best is the combination group. RT-PCR analysis showed that:combination therapy can significantly promote the mRNA expression SCAP, SREBP-2, LDLR in hyperlipidemia rat liver, better than using these two drugs individually. Western blot analysis displayed that combination therapy can significantly promote the LDLR protein expression in hyperlipidemia rat liver.Conclusion:1. Curcumin and niacin in the ratio of2:1has the best regulation of lipid metabolism disturbance effect;2. The hypolipidemic effects can be improved by combining curcumin and niacin [200mg/kg/d+100mg/kg/d], better than using these two drugs individually;3. Combined therapy can decrease hepatic TNF-a and IL-6expression at significant level;4. Hypolipidemic mechanism of combination therapy may be through regulating SCAP-SREBP-2-LDLR pathways.