Premium
Regulation of Hepatic Lipid Metabolism by a Natural Health Product
Author(s) -
Enns Jennifer Emily,
Wu Nan,
Siow Yaw L.,
Karmin O
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.694.5
Subject(s) - berberine , hmg coa reductase , reductase , hydroxymethylglutaryl coa reductase , lipid metabolism , pharmacology , statin , atorvastatin , cholesterol , chemistry , simvastatin , endocrinology , enzyme , medicine , biochemistry
Hypercholesterolemia is a major risk factor for cardiovascular disease. Current treatment for lipid lowering is provided primarily by the statin drugs, which block HMG‐CoA reductase, the rate‐limiting enzyme of cholesterol synthesis, and improve clearance of plasma LDL‐cholesterol. However, many patients cannot tolerate the statin dosages recommended to reach their target lipid levels, due to side effects such as muscle pain and decline in liver function. Berberine, an herbal product used in traditional Chinese medicine, has great potential as a new regulator of lipid metabolism. The objective of this study was to determine whether berberine had an effect on HMG‐CoA reductase and to elucidate the underlying mechanism by which it might act. HMG‐CoA reductase activity was decreased in HepG2 cells after treatment with berberine. The inhibitory effect of berberine on HMG‐CoA reductase was due to post‐translational modification of the enzyme. Western immunoblotting analysis revealed that berberine treatment resulted in a significant increase in the phosphorylation of HMG‐CoA reductase, leading to inactivation of the enzyme. Cells that were treated with berberine exhibited a decrease in cholesterol storage as a result of reduced HMG‐CoA reductase activity. The molecular mechanism by which berberine regulated posttranslational modification of HMG‐CoA reductase was also investigated. Funding: NSERC, CIHR, HSF and MHRC.