Hyperlipidemias: Wei J

Kong W, Wei J, Abidi P, Lin M, Inaba S, Li C, Wang Y, Wang Z, Si S, Pan H, Wang S, Wu J, Wang Y, Li Z, Liu J, Jiang JD. · Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences, and Peking Union Medical College, Beijing, 100050, China. · Nat Med. · Pubmed #15531889 No free full text.

Abstract: We identify berberine (BBR), a compound isolated from a Chinese herb, as a new cholesterol-lowering drug. Oral administration of BBR in 32 hypercholesterolemic patients for 3 months reduced serum cholesterol by 29%, triglycerides by 35% and LDL-cholesterol by 25%. Treatment of hyperlipidemic hamsters with BBR reduced serum cholesterol by 40% and LDL-cholesterol by 42%, with a 3.5-fold increase in hepatic LDLR mRNA and a 2.6-fold increase in hepatic LDLR protein. Using human hepatoma cells, we show that BBR upregulates LDLR expression independent of sterol regulatory element binding proteins, but dependent on ERK activation. BBR elevates LDLR expression through a post-transcriptional mechanism that stabilizes the mRNA. Using a heterologous system with luciferase as a reporter, we further identify the 5' proximal section of the LDLR mRNA 3' untranslated region responsible for the regulatory effect of BBR. These findings show BBR as a new hypolipidemic drug with a mechanism of action different from that of statin drugs.

Kong WJ, Wei J, Zuo ZY, Wang YM, Song DQ, You XF, Zhao LX, Pan HN, Jiang JD. · Department of Pharmacology, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China. · Metabolism. · Pubmed #18640378 No free full text.

Abstract: 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.

Wei J, Ma C, Wang X. · Department of Nephrology, The Second Xiangya Hospital of Central South University, Changsha, Hunan, PR China. · Biomed Res. · Pubmed #16971767 links to  free full text

Abstract: Tissue factor (TF) and plasminogen activator inhibitor-1 (PAI-1) activity and/or expression are upregulated in hypercholesterolemia. Despite extensive research on anti-thrombotic effect of statins, little is known about their effects on TF and PAI-1 expression in glomerular mesangial cells under hypercholesterolemic condition. Male rabbits were fed on either normal or high-cholesterol diet for 8 weeks. Then cholesterol-fed rabbits were randomly assigned to simvastatin or starch. At the end of 12 weeks, glomerular mesangial cells were collected. The concentrations of TF and PAI-1 mRNA were detected by RT-PCR. The plasma activities of TF and PAI-1 were determined with enzyme linked immunosorbent assay (ELISA) and chromogenic substrate method, respectively. The atherogenic diet caused a consistent increase in serum concentrations of total cholesterol (TC) and serum triglyceride (TG) (p < 0.05), increased TF and PAI-1 mRNA expression in glomerular mesangial cells and plasma activities as compared to the normal diet (p < 0.01). Four-week simvastatin treatment resulted in significant decrease of mesangial TF and PAI-1 mRNA (p < 0.01), and also of the plasma activities of TF (p < 0.05) and PAI-1 (p < 0.01). These results suggest that simvastatin might protect kidney from the formation of microthrombus under hypercholesterolemic condition and might be a possible pathogenesis of obesity-related glomerulopathy.