Back to Search
Start Over
Demethyleneberberine attenuates non-alcoholic fatty liver disease with activation of AMPK and inhibition of oxidative stress.
- Source :
-
Biochemical and biophysical research communications [Biochem Biophys Res Commun] 2016 Apr 15; Vol. 472 (4), pp. 603-9. Date of Electronic Publication: 2016 Mar 09. - Publication Year :
- 2016
-
Abstract
- Non-alcoholic fatty liver disease (NAFLD) has reached an epidemic level globally, which is recognized to form non-alcoholic steatohepatitis (NASH) by the "two-hit" model, including oxidative stress and inflammation. AMP-activated protein kinase (AMPK) has long been regarded as a key regulator of energy metabolism, which is recognized as a critical target for NAFLD treatment. Here we introduce a natural product, demethyleneberberine (DMB), which potentially ameliorated NAFLD by activating AMPK pathways. Our study showed that the intraperitoneal injection of DMB (20 or 40 mg/kg body weight) decreased hepatic lipid accumulation in methionine and choline deficient (MCD) high-fat diet feeding mice and db/db mice. The further investigation demonstrated that DMB activated AMPK by increasing its phosphorylation in vitro and in vivo. Accompanied with AMPK activation, the expression of lipogenic genes were significantly reduced while genes responsible for the fatty acid β-oxidation were restored in DMB-treated NAFLD mice. In addition, the remarkable oxidative damage and inflammation induced by NAFLD were both attenuated by DMB treatment, which is reflected by decreased lipid oxidative product, malonaldehyde (MDA) and inflammatory factors, tumor necrosis factor α (TNFα) and interleukin 1β (IL-1β). Based on all above, DMB could serve as a novel AMPK activator for treating NAFLD and preventing the pathologic progression from NAFLD to NASH by inhibiting the oxidative stress and inflammation.<br /> (Copyright © 2016 Elsevier Inc. All rights reserved.)
- Subjects :
- Animals
Berberine therapeutic use
Hep G2 Cells
Humans
Lipid Metabolism drug effects
Liver metabolism
Liver pathology
Male
Mice, Inbred C57BL
Mice, Inbred ICR
Non-alcoholic Fatty Liver Disease metabolism
Non-alcoholic Fatty Liver Disease pathology
AMP-Activated Protein Kinases metabolism
Antioxidants therapeutic use
Berberine analogs & derivatives
Enzyme Activation drug effects
Liver drug effects
Non-alcoholic Fatty Liver Disease drug therapy
Oxidative Stress drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1090-2104
- Volume :
- 472
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Biochemical and biophysical research communications
- Publication Type :
- Academic Journal
- Accession number :
- 26970305
- Full Text :
- https://doi.org/10.1016/j.bbrc.2016.03.019