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Berberine is a novel cholesterol-lowering drug working through a unique mechanism distinct from statins

Nature Medicine volume 10, pages 13441351 (2004) | Download Citation

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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.

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Acknowledgements

We thank F. B. Kraemer for his review of the manuscript and S. M. Prescott for providing the pLuc plasmid. This study was supported by the National Natural Sciences Foundation of China (39925037, 39870889 & 39930190; J.-D.J.), by the Department of Veterans Affairs (Office of Research and Development, Medical Research Service; J. Liu) and by grant (1RO1CA83648-01; J.L.) from United States National Institute of Health.

Author information

Author notes

    • Weijia Kong
    • , Jing Wei
    •  & Parveen Abidi

    These authors contributed equally to this work.

Affiliations

  1. Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences, and Peking Union Medical College, Beijing, 100050, China.

    • Weijia Kong
    • , Shuyi Si
    • , Zhuorong Li
    •  & Jian-Dong Jiang
  2. Division of Endocrinology and Laboratory of Molecular Medicine, First Hospital of Nanjing City, Nanjing Medical University, Nanjing, 210006, China.

    • Jing Wei
    • , Zizheng Wang
    • , Huaining Pan
    • , Shukui Wang
    •  & Jingdan Wu
  3. Research Service, Department of Veterans Affairs Palo Alto Health Care System, Palo Alto, CA, 94304, USA.

    • Parveen Abidi
    • , Meihong Lin
    • , Satoru Inaba
    • , Cong Li
    •  & Jingwen Liu
  4. Department of Medicine, Mount Sinai School of Medicine, New York, NY, 10029, USA.

    • Yanling Wang
    • , Yue Wang
    •  & Jian-Dong Jiang

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The authors declare no competing financial interests.

Corresponding authors

Correspondence to Jingwen Liu or Jian-Dong Jiang.

Supplementary information

PDF files

  1. 1.

    Supplementary Table 1

    Effects of BBR in the entire hypercholesterolemic patient cohort

  2. 2.

    Supplementary Table 2

    Characterization of the subgroup of hypercholesterolemic patients who were not taking other medication before or during BBR treatment

  3. 3.

    Supplementary Table 3

    Lipid-lowering effect of BBR in hypercholesterolemia Type IIa & IIb

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DOI

https://doi.org/10.1038/nm1135

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