Demethyleneberberine, a Natural Mitochondria-Targeted Antioxidant, Inhibits Mitochondrial Dysfunction, Oxidative Stress, and Steatosis in Alcoholic Liver Disease Mouse Model
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.
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Consumption of anti-inflammatory antioxidants from natural dietary supplements and/or synthetic origins can help reduce the incidence and severity of AGE-associated inflammation and related disorders.
“Furthermore, consumption of anti-inflammatory antioxidants from natural dietary supplements279,281,282,290 and/or synthetic origins199 can help reduce the incidence and severity of AGE-associated inflammation and related disorders.”
From Advanced glycation end products (AGEs) and other adducts in aging-related diseases and alcohol-mediated tissue injury (2021) · cites this paper as [279]
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- Authors
- Zhang, P., Qiang, X., Zhang, M., Ma, D., Zhao, Z., Zhou, C., Liu, X., Li, R., Chen, H., & Zhang, Y.
- Affiliations
- China Pharmaceutical University (CN)
- ORCID
- Venue
- The Journal of Pharmacology and Experimental Therapeutics
- Publisher
- Elsevier BV
- Published
- 2015-01
- Volume
- 352
- Issue
- 1
- Pages
- 139-147
- ISSN
- 0022-3565 (ISSN-L)
- OpenAlex
- W1990309009
- Cited by
- 78
- References
- 43
- Citations by year
- 2026: 3 · 2025: 6 · 2024: 5 · 2023: 7 · 2022: 11 · 2021: 10 · 2020: 7 · 2019: 4 · 2018: 3 · 2017: 11 · 2016: 5 · 2015: 6
- FWCI
- 5.42
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Pharmacology and Experimental Therapeutics (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Pathology and Forensic Medicine › Alcohol Consumption and Health Effects
- Health Sciences › Medicine › Pharmacology › Berberine and alkaloids research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Keywords
- alcoholic liver disease, mitochondria-targeted antioxidants, oxidative stress, mitochondrial dysfunction, steatosis, lipid peroxidation, ethanol-induced liver injury, CYP2E1, hypoxia-inducible factor alpha, inducible nitric oxide synthase, fatty acid oxidation, MitoQ
- MeSH terms
- Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha, Ethanol, Animals, Antioxidants, Berberine, Disease Models, Animal, Fatty Acids, Humans, Liver Diseases, Alcoholic, Male, Mitochondria, Oxidation-Reduction, Transcription Factors, Signal Transduction, Oxidative Stress, Cytochrome P-450 CYP2E1, Mice, Hypoxia-Inducible Factor 1, alpha Subunit, Nitric Oxide Synthase Type II, AMP-Activated Protein Kinases, Sirtuin 1, Hep G2 Cells
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