Back to Search
Start Over
Demethyleneberberine, a natural mitochondria-targeted antioxidant, inhibits mitochondrial dysfunction, oxidative stress, and steatosis in alcoholic liver disease mouse model.
- Source :
-
The Journal of pharmacology and experimental therapeutics [J Pharmacol Exp Ther] 2015 Jan; Vol. 352 (1), pp. 139-47. Date of Electronic Publication: 2014 Oct 31. - Publication Year :
- 2015
-
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.<br /> (Copyright © 2014 by The American Society for Pharmacology and Experimental Therapeutics.)
- Subjects :
- AMP-Activated Protein Kinases metabolism
Animals
Antioxidants therapeutic use
Berberine pharmacology
Berberine therapeutic use
Cytochrome P-450 CYP2E1 metabolism
Disease Models, Animal
Ethanol adverse effects
Fatty Acids metabolism
Hep G2 Cells
Humans
Hypoxia-Inducible Factor 1, alpha Subunit antagonists & inhibitors
Liver Diseases, Alcoholic drug therapy
Liver Diseases, Alcoholic etiology
Male
Mice
Mitochondria metabolism
Nitric Oxide Synthase Type II antagonists & inhibitors
Oxidation-Reduction drug effects
Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
Signal Transduction drug effects
Sirtuin 1 metabolism
Transcription Factors metabolism
Antioxidants pharmacology
Berberine analogs & derivatives
Liver Diseases, Alcoholic metabolism
Liver Diseases, Alcoholic pathology
Mitochondria drug effects
Oxidative Stress drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1521-0103
- Volume :
- 352
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- The Journal of pharmacology and experimental therapeutics
- Publication Type :
- Academic Journal
- Accession number :
- 25362106
- Full Text :
- https://doi.org/10.1124/jpet.114.219832