Combination of simvastatin with berberine improves the lipid-lowering efficacy.
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.
Kong
Wei-Jia
WJ
Department of Pharmacology, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
Wei
Jin
J
Zuo
Zeng-Yan
ZY
Wang
Yue-Ming
YM
Song
Dan-Qing
DQ
You
Xue-Fu
XF
Zhao
Li-Xun
LX
Pan
Huai-Ning
HN
Jiang
Jian-Dong
JD
D000818:Animals; D001599:Berberine / Q000494:pharmacology* / Q000627:therapeutic use; D008078:Cholesterol, LDL / Q000097:blood; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D005234:Fatty Liver / Q000188:drug therapy / Q000378:metabolism; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D006937:Hypercholesterolemia / Q000097:blood / Q000188:drug therapy*; D008297:Male; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D011973:Receptors, LDL / Q000096:biosynthesis / Q000235:genetics; D019821:Simvastatin / Q000494:pharmacology* / Q000627:therapeutic use; D014280:Triglycerides / Q000097:blood; D015854:Up-Regulation / Q000187:drug effects
D008078:Cholesterol, LDL; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D012333:RNA, Messenger; D011973:Receptors, LDL; D014280:Triglycerides; D001599:Berberine; D019821:Simvastatin