Volume 29, Issue S1 885.7
Biochemistry and Molecular Biology
Free Access

Demethyleneberberine Attenuates Free Fatty Acid- And High Fat Diet-Induced Hepatic Lipotoxicity By Activating AMP-Activated Protein Kinase

Xiaoyan Qiang

Xiaoyan Qiang

Biochemistry, China Pharmaceutical University, Nanjing, Jiangsu, China

Microbiolgy and Immunology Virginia Commonwealth University, Richmond, VA, United States

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Lulu Xu

Lulu Xu

Biochemistry, China Pharmaceutical University, Nanjing, Jiangsu, China

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Pengcheng Zhang

Pengcheng Zhang

Biochemistry, China Pharmaceutical University, Nanjing, Jiangsu, China

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Yubin Zhang

Yubin Zhang

Biochemistry, China Pharmaceutical University, Nanjing, Jiangsu, China

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Huiping Zhou

Huiping Zhou

Microbiolgy and Immunology Virginia Commonwealth University, Richmond, VA, United States

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First published: 01 April 2015
Citations: 1

Abstract

Non-alcoholic fatty liver disease (NAFLD) is one of the most common causes of chronic liver disease. It refers to a spectrum of conditions associated with lipid accumulation in hepatocytes. Berberine (BBR), an isoquinoline alkaloid isolated from many medicinal herbs, has been used to treat various diseases including liver diseases. Our previous studies have shown that BBR could prevent hepatic lipid accumulation. However, its biological function is limited by its low oral bioavailability and fast metabolism. This study was to examine the effect of a natural product and a major active metabolite of BBR, demethyleneberberine (DMB), on hepatic lipid accumulation and further identify the potential underlying molecular mechanisms.

Methods

Palmitic acid (PA)-treated HepG2 cells, methionine and choline deficient (MCD) high-fat diet mice, and db/db mice were used in this study. The MCD mice and ob/ob mice were ip injected with DMB (20 or 40 mg/kg) for 4-weeks. The livers were stained with Oil Red O to detect lipid. Activation of AMP-activated protein kinase (AMPK) was determined by Western blot analysis. The liver enzymes and serum lipids were measured using commercial kits. The liver histology was examined after HE staining.

Results

DMB activated AMPK in both in vitro and in vivo NAFLD models. In addition, PA- and MCD-induced hepatic oxidative stress and inflammation as well as lipid accumulation were markedly reduced by DMB.

Conclusion

DMB attenuates PA- and MCD-induced lipotoxicity probably via the activation of the AMPK signaling pathway.