期刊
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
卷 472, 期 4, 页码 603-609出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2016.03.019
关键词
Demethyeneberberine; Non-alcoholic liver disease; Hepatosteatosis; AMPK; Oxidative stress; Inflammation
资金
- National Natural Science Foundation of China grant [81573484]
- Project of State Key Laboratory of Natural Medicines, China Pharmaceutical University [SKLNMZZC201407]
- Graduate Innovation Project of Jiangsu Province to Xiaoyan Qiang [CXZZ13-0355]
- Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD)
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 beta-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 alpha (TNF alpha) and interleukin 1 beta (IL-beta). 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. (C) 2016 Elsevier Inc. All rights reserved.
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