Tetrahydroxystilbene glucoside protects against ethanol-induced liver injury in mice by inhibition of expression of inflammation-related factors

AIM:To investigate the protective effects of tetrahydroxystilbene glucoside(TSG) against acute ethanol-induced liver injury in mice and to explore the possible mechanisms involved.METHODS:Kunming mice were randomly divided into five groups:normal control group,liver injury model group,low-(30mg/kg) and high-dose(60mg/kg) TSG groups,and Silibinin(50mg/kg) group.Liver histopathology was measured by light microscopy.The contents of serum tumor necrosis factor-α(TNF-α),interleukin 1β(IL-1β),and IL-6 were assayed by ELSIA,and plasma endotoxin level was measured by LAL chromogenic endpoint assay.The mRNA expression of TNF-α and iNOS in liver tissue was detected by real-time PCR.The phospho-IκBα level and NF-κB nuclear translocation in hepatic tissue were measured by Western blot.RESULTS:Compared to the control group,the model group showed significant hydropic degeneration and steatosis of hepatocytes,increased contents of serum TNF-α,IL-1β and IL-6 and plasma level of endotoxin(all P0.01),up-regulated mRNA expression of TNF-α and iNOS in liver tissue(TNF-α:128.5pg/mL±20.7pg/mL vs 45.2pg/mL±14.2pg/mL;IL-1β:71.8pg/mL ±9.1 pg/mL vs 33.1pg/mL±9.5pg/mL;IL-6:59.8pg/mL±13.1pg/mL vs 23.7pg/mL±5.9pg/mL;endotoxin:0.35EU/mL±0.09EU/mL vs 0.11EU/mL±0.03EU/mL.TNF-α mRNA:1.33±0.11 vs 0.63±0.10;iNOS mRNA:0.85±0.09 vs 0.40±0.07;phospho-IκB-α:2.02±0.14 vs 0.92±0.19;NF-κB P65:1.10±0.14 vs 0.44±0.13,P0.05,P0.01),and significantly increased phospho-IκBα level and NF-κB nuclear translocation in hepatic tissue(both P0.01).Compared to the model group,serum levels of TNF-α,IL-1β and IL-6 and plasma endotoxin level significantly decreased(all P0.05 or 0.01),the mRNA expression of TNF-α and iNOS was down-regulated,and phospho-IκBα level and NF-κB nuclear translocation in hepatic tissue were significantly inhibited in the TSG groups(TSG 60 mg/kg group:TNF-α:65.9pg/mL±13.9pg/mL vs 128.5pg/mL±20.7pg/mL;IL-1β:43.0pg/mL±7.1pg/mL vs 71.8pg/mL±9.1pg/mL;IL-6:36.3pg/mL±10.1pg/mL vs 59.8pg/mL±13.1pg/mL;endotoxin:0.20EU/mL±0.05EU/mL vs 0.35EU/mL±0.09EU/mL;TNF-α mRNA:0.79±0.09 vs 1.33±0.11;iNOS mRNA:0.53±0.10 vs 0.85±0.09;phospho-IκB-α:1.35±0.32 vs 2.02±0.14;NF-κB P65:0.62±0.05 vs 1.10±0.14,all P0.05 or 0.01).CONCLUSION:TSG has a protective effect on acute alcoholic liver injury in mice possibly by decreasing endotoxin level and NF-κB nuclear translocation and attenuating the trigger of inflammation-related cascade amplification.