Author: ["Weijia Kong","Jing Wei","Parveen Abidi","Meihong Lin","Satoru Inaba","Cong Li","Yanling Wang","Zizheng Wang","Shuyi Si","Huaining Pan","Shukui Wang","Jingdan Wu","Yue Wang","Zhuorong Li","Jingwen Liu","Jian-Dong Jiang"]
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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.Cite this article
Kong, W., Wei, J., Abidi, P. et al. Berberine is a novel cholesterol-lowering drug working through a unique mechanism distinct from statins. Nat Med 10, 1344–1351 (2004). https://doi.org/10.1038/nm1135 