The Effect And Mechanism Of Bisdemethoxycurcumin On Carbon Tetrachloride-Induced Acute Liver Injury In Mice

Aim:Bidemethoxycurcumin?BDMC?is one of the main components of curcuminoids,which is confirmed to exert the effects of anti-inflammatory,anti-oxidation and anti-tumor.In this study,a mouse model of acute liver injury induced by carbon tetrachloride?CCl₄?was used to evaluate the the effect and mechanism of BDMC,which could provide experimental evidence for the clinical application of BDMC.Methods:1.To study the effect of BDMC on liver injury induced by CCl₄ in mice.72KM mice were randomly divided into six groups:CON group,MODEL group,BDD100group,BDMC12.5,BDMC25 and BDMC50 group.The animals in CON and MODEL groups were administered with 0.5%?w/v?sodium carboxymethyl cellulose.For the other groups,the drug was given once a day by gavage for 14 consecutive days with a volume of 20 ml/kg.0.2%CCl₄ were used to make acute liver injury mice model except CON group after 1 h at the last administration?i.p.?.After 24 h,the activities of aspartate aminotransferase?AST?,alanine aminotransferase?ALT?and lactate dehydrogenase?LDH?in serum were determined.Dissect and separate the liver and spleen and its indexes were detected.HE staining of part of liver was observed to detect the pathological changes.2.To study the mechanism of protective effect of BDMC on CCl₄induced liver injury.72 male KM mice were grouped and administered in the same way as before.The level of TNF-?and IL-1?of liver and serum were assayed.The activity of SOD and the levels of GSH and MDA of liver were assayed.The expression of PPAR-?,iNOS,NF-?B,p-NF-?B,p-JAK2,JAK2,p-STAT3,STAT3,Bax,Bcl-2 and cleaved caspase-3 were detected by western blot.Results:1?1?Compared with the CON group,the activities of AST,ALT and LDH were increased in the MODEL group?P<0.01?.Compared with the MODEL group,the activities of AST,ALT and LDH were decreased in the BDD100 group?P<0.05,P<0.01?;the activity of ALT were decreased in the BDMC12.5 group?P<0.05?;the activities of AST,ALT and LDH were decreased in the BDMC25 and BDMC50 groups?P<0.05,P<0.01?.?2?Compared with the CON group,the indexes of liver and spleen were increased in the MODEL group?P<0.01?.Compared with the MODEL group,the indexes of liver and spleen were decreased in the BDMC50 group?P<0.05?.?3?The pathological changes were observed in the MODEL group,such as hepatic cord disorder,hepatocyte swelling,inflammatory cell infiltration and partial cell necrosis.BDD and BDMC improved the histopathological changes in mice of MODEL group.2?1?Compared with the CON group,the levels of TNF-?and IL-1?were increased in the MODEL group?P<0.05,P<0.01?.Compared with the MODEL group,the level of IL-1?in liver and TNF-?in liver and serum were decreased in the BDD100 group?P<0.05,P<0.01?;the levels of TNF-?and IL-1?were increased in the MODEL group?P<0.05,P<0.01?.Compared with the MODEL group,the level of TNF-?in liver in BDMC50,TNF-?and IL-1?in liver and serum in BDMC25 and BDMC50 groups were decreased?P<0.05,P<0.01?.?2?Compared with the CON group,the activity of SOD and level of GSH were decreased?P<0.01?,the level of MDA was increased in the MODEL group.Compared with the MODEL group,the activity of SOD were increased in BDD100 and BDMC50 groups?P<0.05,P<0.01?;the level of GSH were increased in BDD100,BDMC25 and BDMC50 groups?P<0.05,P<0.01?;the level of MDA was increased in BDD100 and BDMC50 groups?P<0.05?;?3?Compared with the CON group,the expression of PPAR-?was decreased,the expression of iNOS,p-NF-?B/NF-?B,p-JAK2/JAK2,p-STAT3/STAT3,Bax/Bcl-2 and cleaved caspase-3were increased in MODEL groups?P<0.01?.Compared with the MODEL group,the expression of PPAR-?was increased?P<0.01?,p-NF-?B/NF-?B,p-JAK2/JAK2 and p-STAT3/STAT3 were decreased?P<0.05,P<0.01?in BDD100 and BDMC50 groups.The ratio of p-JAK2/JAK2 and p-STAT3/STAT3 were decreased?P<0.05,P<0.01?in BDMC25 and BDMC50 groups?P<0.01?.The iNOS,Bax/Bcl-2 and cleaved caspase-3were decreased in BDMC12.5,BDMC25 and BDMC50 groups?P<0.05,P<0.01?.Conclusion:1.BDMC can exert hepatoprotective effects on CCl₄-induced acute liver injury in mice.2.The mechanism of protective effect of BDMC on CCl₄-induced acute liver injury in mice may be involved by anti-apoptosis and inhibition of inflammation and oxidative stress by PPAR-?regulation of NF-?B and JAK2/STAT3 signaling pathways.