【摘 要】
：
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 B
【机 构】
：
Department of Microbiology, Wu Lien-Teh Institute, Harbin Medical University, Harbin 150081, China;D
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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-1 had 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 ethanolfed 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.
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