Abstract
Excessive alcohol consumption induces oxidative stress and lipid accumulation in the liver. Mitochondria have long been recognized as the key target for alcoholic liver disease (ALD). Recently, the artificial mitochondria-targeted antioxidant MitoQ has been used to treat ALD effectively in mice. Here, we introduce the natural mitochondria-targeted antioxidant demethyleneberberine (DMB), which has been found in Chinese herb Cortex Phellodendri chinensis. The protective effect of DMB on ALD was evaluated with HepG2 cells and acutely/chronically ethanol-fed mice, mimicking two common patterns of drinking in human. The results showed that DMB, which is composed of a potential antioxidant structure, could penetrate the membrane of mitochondria and accumulate in mitochondria either in vitro or in vivo. Consequently, the acute drinking–caused oxidative stress and mitochondrial dysfunction were significantly ameliorated by DMB. Moreover, we also found that DMB suppressed CYP2E1, hypoxia inducible factor α, and inducible nitric oxide synthase, which contributed to oxidative stress and restored sirtuin 1/AMP-activated protein kinase/peroxisome proliferator–activated receptor-γ coactivator-1α pathway–associated fatty acid oxidation in chronic ethanol-fed mice, which in turn ameliorated lipid peroxidation and macrosteatosis in the liver. Taking these findings together, DMB could serve as a novel and potential therapy for ALD in human beings.
Footnotes
- Received September 9, 2014.
- Accepted October 30, 2014.
This work was supported by the National Natural Science Foundation of China [Grant 81072679] to Yubin Zhang; the Project of the State Key Laboratory of Natural Medicines, China Pharmaceutical University [Grant No. SKLNMZZC201407]; the Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD); the College Students Innovation Project for the R&D of Novel Drugs [Grant J1030830]; and the Graduate Students Research Innovation Project in Jiangsu Province [Grant KYZZ_0190].
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- Copyright © 2014 by The American Society for Pharmacology and Experimental Therapeutics
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