Nature Medicine
10, 1344 - 1351 (2004)
Published online: 7 November 2004; | doi:10.1038/nm1135
Berberine is a novel cholesterol-lowering drug working through a unique mechanism distinct from statinsWeijia Kong1, 5, Jing Wei2, 5, Parveen Abidi3, 5, Meihong Lin3, Satoru Inaba3, Cong Li3, Yanling Wang4, Zizheng Wang2, Shuyi Si1, Huaining Pan2, Shukui Wang2, Jingdan Wu2, Yue Wang4, Zhuorong Li1, Jingwen Liu3
& Jian-Dong Jiang1, 41
Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences, and Peking Union Medical College, Beijing, 100050, China. 2
Division of Endocrinology and Laboratory of Molecular Medicine, First Hospital of Nanjing City, Nanjing Medical University, Nanjing, 210006, China. 3
Research Service, Department of Veterans Affairs Palo Alto Health Care System, Palo Alto, CA, 94304, USA. 4
Department of Medicine, Mount Sinai School of Medicine, New York, NY, 10029, USA. 5
These authors contributed equally to this work.
Correspondence should be addressed to Jian-Dong Jiang jiandong.jiang@mssm.edu or Jingwen Liu jingwen.liu@med.va.govWe 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.
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