The Effects Of Curcumin Derivative On Experimental Satohepatitis

Objective To observe and compare the effects of curcumin and its derivative on experimental non-alcoholic steatohepatitis (NASH).Methods (1) Establishment of rat NASH model: 60 SD male rats were randomly divided into 5 groups(12 rats/group): normal group(A),model group(B),saline group(C),curcumin group(D) and curcumin derivative group(E).A group was fed with normal diet. Other groups fed with high fat diet containing 79.5% corn,20% lard,0.5% cholesterol. The rats of B,C,D,E group were subcutaneously injected with a mixture of CCl₄ and paraffin oil [(2:3)v/v], 3 ml / kg, twice per week for 6 weeks; After 6 weeks, 3 rats in each of A and B group were killed to observe modeling results through serum and liver pathological examination.(2) Examine the effect and the relative mechanism of curcumin and its derivatives on NASH: After 6 weeks of modeling, rats of A and B group were sacrificed. At the same time, rats of D group were orally given curcumin at 50mg/kg for 2 weeks by gavages, once daily; rats of C and E group were injected intravenously with saline and curcumin derivatives for 2 weeks at the same dose and frequency. During the experiment, all rats were weighed once a week to adjust the dose of CCl₄. After 2 weeks for treatment, all rats were killed for collecting blood and livers. At last, activities of serum ALT,AST,TG,TCH were analyzed .Pathological changes were observed by HE staining and oil red O staining. And the expression of TNF-α,NF-κB,FAS,HMG-CoA reductase mRNA and TNF-α,NF-κB protein in liver tissues were examined.Results (1)Except the normal group, all rats'liver index were more than 5%, met the diagnostic requirements of the fatty liver. Liver index in model group were significantly higher than normal group, the difference was statistically significant (P <0.05). HE staining showed that liver tissues of model group had apparent fatty degeneration, inflammation, necrosis and bleeding, even fibrosis in some liver portal areas. Its steatosis and inflammation were almost the most advanced in the 5 groups, but fibrosis were mild. Compared with the normal group, the levels of serum ALT,AST,TCH of model group were significantly elevated (P<0.05); the expression of TNF-α,NF-κB,FAS,HMG-CoA reductase mRNA and TNF-α,NF-κB proteins were similar in model group.(2) Compared with model group, the liver index decreased in curcumin or curcumin derivatives-treated rats, the difference was statistically significant (P <0.05). There was a remarkable reduction in serum ALT,AST,TCH in rats treated with curcumin and its derivatives group vs saline group(P <0.05). And the levels of ALT,AST were significantly lower in curcumin derivatives group vs curcumin group(P <0.05). But TG have no significant changes after treatment (P>0.05). HE staining showed that the liver steatosis and inflammation grade of curcumin derivatives group were significantly improved compared with model group, and the levels of fibrosis of curcumin derivatives group were improved compared with the saline group(P <0.05). But there were no difference in pathological changes between curcumin group and model group(P>0.05). The gene transcription of TNF-α,NF-κB,FAS,HMG-CoA reductase mRNA in curcumin derivatives group were significantly lower than those in saline group or in curcumin group(P<0.05).Curcumin and its derivatives also significantly reduced TNF-α, NF-κB protein expression, especially the curcumin derivatives.Conclusions Compared with traditional curcumin, the water-soluble curcumin derivative effectively limits the development and progression of fibrosis and improves lipid metabolism in rats with experimental steatohepatitis.