Berbamine ameliorates ethanol-induced liver injury by inhibition of hepatic inflammation in mice
| Autor: | Wuqi Song, Ting-Wang Jiang, Xin-Yu Liu, Hailiang Liu, Guo-Ming Du, Yue Pan, Guan-Nan Chen |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
MAPK/ERK pathway
STAT3 Transcription Factor Alcoholic liver disease Lipopolysaccharide MAP Kinase Signaling System p38 mitogen-activated protein kinases Inflammation Pharmacology Berbamine 01 natural sciences Benzylisoquinolines 03 medical and health sciences chemistry.chemical_compound Mice 0302 clinical medicine Drug Discovery medicine Oil Red O Animals Triglycerides Liver injury Ethanol 010405 organic chemistry NF-kappa B General Medicine medicine.disease Lipid Metabolism 0104 chemical sciences Mice Inbred C57BL Cholesterol RAW 264.7 Cells Complementary and alternative medicine chemistry Liver 030220 oncology & carcinogenesis Chemical and Drug Induced Liver Injury Chronic Hepatocytes Cytokines Female medicine.symptom |
| Zdroj: | Chinese journal of natural medicines. 18(3) |
| ISSN: | 1875-5364 |
| Popis: | Alcoholic liver disease (ALD) has become one of the leading causes of death in the world. Berbamine (BM), a natural product mainly derived from Berberis vulgaris L, possesses multiple bioactivities as a traditional medicine. However, the protective effect of BM on ALD remains unknown. In this study, we investigated the effect of BM on ethanol-induced hepatic injury in mice and its underlying mechanism. It was shown that BM at 0.3125-40 μmol·L-1had no effect on macrophages and hepatocytes proliferation. BM at 5-20 μmol·L-1 significantly inhibited lipopolysaccharide (LPS) or acetate-induced IL-1β and IL-6 mRNA expression in RAW264.7 cells. Moreover, BM treatment significantly inhibited LPS-induced p65 and STAT3 phosphorylation in RAW264.7 cells. Hepatic histopathology analysis showed that inflammatory cells infiltration and lipid accumulation were suppressed by 25 and 50 mg·kg-1 BM administration in ethanol-induced hepatic injury mouse model. Meanwhile, BM treatment significantly inhibited serum ALT and AST levels in ethanol-fed mice. Oil red O staining results showed that BM administration ameliorated hepatic lipid accumulation in ethanol-fed mice. Preventions of ethanol-induced hepatic injury by BM were reflected by markedly decreased serum and hepatic triglyceride (TG) and total cholesterol (TC) contents. Real-time PCR results showed that BM treatment significantly inhibited pro-inflammatory cytokines mRNA expression in ethanol-fed mouse liver. Remarkably, the mechanism of action of BM was related to the reduction of ethanol-induced NF-κB and STAT3 phosphorylation levels in liver. In addition, BM treatment significantly inhibited ERK phosphorylation but not JNK and p38 of MAPK pathway. Taken together, our results demonstrate a beneficial effect of BM on ethanol-induced liver injury via a mechanism associated with inactivation of NF-κB, STAT3 and ERK pathway, which gives insight into the further evaluation of the therapeutic potential of BM for ALD. |
| Databáze: | OpenAIRE |
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