Demethyleneberberine attenuates non-alcoholic fatty liver disease with activation of AMPK and inhibition of oxidative stress.

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.

• Authors: Xiaoyan Qiang, Lulu Xu, Miao Zhang, Pengcheng Zhang, Yinhang Wang, Yongchen Wang, Zheng Zhao, Huan Chen, Xie Liu, Yubin Zhang
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 472 Issue 4 Pg. 603-9 (Apr 15 2016) ISSN: 1090-2104 [Electronic] United States
• PMID: 26970305 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2016 Elsevier Inc. All rights reserved.

Chemical References

• Antioxidants
• Berberine
• demethyleneberberine
• AMP-Activated Protein Kinases

Topics

• AMP-Activated Protein Kinases (metabolism)
• Animals
• Antioxidants (therapeutic use)
• Berberine (analogs & derivatives, therapeutic use)
• Enzyme Activation (drug effects)
• Hep G2 Cells
• Humans
• Lipid Metabolism (drug effects)
• Liver (drug effects, metabolism, pathology)
• Male
• Mice, Inbred C57BL
• Mice, Inbred ICR
• Non-alcoholic Fatty Liver Disease (drug therapy, metabolism, pathology)
• Oxidative Stress (drug effects)