Combination of simvastatin with berberine improves the lipid-lowering efficacy
Combination of simvastatin with berberine improves the lipid-lowering efficacy
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DOI：
10.1016/j.metabol.2008.01.037
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发表时间：
2008-08-01
影响因子：
9.8
通讯作者：
Jiang, Jian-Dong
中科院分区：
文献类型：
--
作者：
Kong, Wei-Jia;Wei, Jin;Jiang, Jian-Dong
我们已经确定小檗碱（BBR）作为一种新型的降胆固醇药物，通过稳定低密度脂蛋白受体（LDLR）信使RNA的作用。由于其机制与他汀类药物不同，因此研究BBR与他汀类药物联合使用的降脂活性具有重要意义。我们的研究结果表明，BBR与辛伐他汀（SIMVA）的组合增加LDLR基因的表达水平显着高于单药治疗。在治疗食物诱导的高血压大鼠中，BBR联合（90 mg/[kg d]，经口）与SIMVA（6 mg/[kg d]，口服）降低血清LDL胆固醇46.2%，比SIMVA（28.3%）或BBR（26.8%）单药治疗更有效（两者均P <0.01），与SIMVA 12 mg/（kg d）（43.4%）相似。与任一单药治疗相比，联合治疗也能更有效地降低血清甘油三酯。BBR与SIMVA的组合上调大鼠肝脏中的LDLR信使RNA至比单药治疗高约1.6倍的水平。联合治疗后发现肝脏脂肪储存显著减少，肝脏组织学改善。然后在63例高胆固醇血症患者中评价了联合治疗的疗效。与单药治疗相比，联合治疗显示出改善的降脂效果，血清LDL胆固醇降低31.8%（与单独BBR相比P <0.05，与单独SIMVA相比P <0.01）。在降低患者总胆固醇和甘油三酯方面观察到类似的疗效。我们的研究结果显示了使用BBR和SIMVA联合治疗高脂血症的合理性、有效性和安全性。这可能是治疗高胆固醇血症的新方法。(C)2008年爱思唯尔公司All rights reserved.
We have identified berberine (BBR) as a novel cholesterol-lowering drug acting through stabilization of the low-density lipoprotein receptor (LDLR) messenger RNA. Because the mechanism differs from that of statins, it is of great interest to examine the lipid-lowering activity of BBR in combination with statins. Our results showed that combination of BBR with simvastatin (SIMVA) increased the LDLR gene expression to a level significantly higher than that in monotherapies. In the treatment of food-induced hyperlipidemic rats, combination of BBR (90 mg/[kg d], oral) with SIMVA (6 mg/[kg d], oral) reduced serum LDL cholesterol by 46.2%, which was more effective than that of the SIMVA (28.3%) or BBR (26.8%) monotherapy (P < .01 for both) and similar to that of SIMVA at 12 mg/(kg d) (43.4%). More effective reduction of serum triglyceride was also achieved with the combination as compared with either monotherapy. Combination of BBR with SIMVA up-regulated the LDLR messenger RNA in rat livers to a level about 1.6-fold higher than the monotherapies did. Significant reduction of liver fat storage and improved liver histology were found after the combination therapy. The therapeutic efficacy of the combination was then evaluated in 63 hypercholesterolemic patients. As compared with monotherapies, the combination showed an improved lipid-lowering effect with 31.8% reduction of serum LDL cholesterol (P < .05 vs BBR alone, P < .01 vs SIMVA alone). Similar efficacies were observed in the reduction of total cholesterol as well as triglyceride in the patients. Our results display the rationale, effectiveness, and safety of the combination therapy for hyperlipidemia using BBR and SIMVA. It could be a new regimen for hypercholesterolemia. (C) 2008 Elsevier Inc. All rights reserved.