The amphiphilic curcumin derivative attenuates liver fibrosis by anti-inflammatory and antioxidant effect / 中国药理学通报

ABSTRACT

Aim To investigate the effects of anti-in-flammation and antioxidation of an amphiphilic curcu-min derivative (Curc-OEG)on CCl4-induced hepatic fibrosis in rats.Methods Rats were randomly divided into four groupscontrol group,model group,curcumin and Curc-OEG treatment group.All rats except those in control group were given subcuta-neous injection of CCl4 and olive oil mixture,twice a week for 8 weeks.After 4 weeks,rats of control and model group were trea-ted with normal saline intravenously,curcumin group were ad-ministered with curcumin 400 mg.kg -1 .d -1 by gavage and Curc-OEG group were treated with Curc-OEG 1 00 mg.kg -1 .d -1 intra-venously respectively.After 4 weeks treatment,the serum levels of ALT and AST were tested.HE and Sirus staining were used to evaluate the extent of liver inflammation and fibrosis.The mRNA expression levels of proinflammatory cytokines of NF-kB,IL-1 β, IL-6,TNF-α,COX-2 were observed with Real Time PCR.The level of MOD,SOD and GSH in liver of rats were quantified. Results The levels of ALT in control,model,curcumin and Curc-OEG group was (31 .7 ±8.7)U·L -1 ,(383.0 ±75.6) U·L -1 ,(406.3 ±204.7)U·L -1 ,(1 07.0 ±73.7)U·L -1 respectively;that of AST was (1 37.7 ±32.7)U·L -1 ,(585.3 ±36.7)U·L -1 ,(485.0 ±246.5)U·L -1 ,(202.7 ±56.0) U·L -1 respectively,Curc-OEG possessed more hepatoprotective effects than that of curcumin.Liver pathology showed Curc-OEG treatment could significantly alleviate steatosis,reduce inflamma-tion and apparently suppress hepatic fibrogenesis by reducing the thickness of bridging fibrotic septa.Compared with curcumin, Curc-OEG down-regulated mRNA and protein expression levels of NF-kB,IL-1 β,IL-6,TNF-α,COX-2 (P <0.05 ).Moreo-ver,Curc-OEG reduced the level of MOD and increased the lev-els of SOD and GSH.Conclusion Curc-OEG could more sig-nificantly protect the rat liver from CCl4-caused fibrogenesis by anti-inflammatory and antioxidant effect than curcumin.