Effects Of Curcumin On Nonalcoholic Steatohepatitis In Rats And Its Mechanisms

Objective: To investigate the prevention and treatment effects of curcumin on high-fat dietinduced nonalcoholic steatohepatitis in rats and its mechanisms.Materials and methods: Thirty-six SD rats were randomly divided into normal group,model group and treatment group with twelve each. Rats in normal group were fed with astandard diet while those in other two groups received a high-fat diet. Two rats from eachgroup were executed at the end of the sixth week to detect the pathological changes. Then,rats in treatment group were gavaged with50mg/kg of curcumin daily. Those in normalgroup and model group received an equal volume of0.5%CMC as control. At the end ofthe twelfth week，all rats were executed. Blood and liver samples were collected. The bodyweight, liver weight, liver index and liver function of the each group rats were recordedand analyzed. The liver histological changes were observed by both hematoxylin and eosin(H&E) staining and Oil red O (ORO) staining. The levels of serum lipid, homeostasismodel assessment of insulin resistance (HOMA-IR) and oxidative stress status in liverwere measured by corresponding methods. The contents of inflammation related cytokinessuch as TNF-α, IL-6were measured by enzyme-link immunosorbent analysis (ELlSA).The protein and mRNA expressions of liver HO-1were detected by immunohistochemistryand RT-PCR, respectively. The expressions of Nrf2protein in liver cell nucleus weredetermined by Western blot.Results: Steatosis, ballooning, mixed acute and chronic lobular inflammation and focalnecrosis were presented in model group rats accompanied by elevated serum ALT, ASTlevels (P<0.05). Rats in model group had higher levels of serum TG, TC, FFA, HOMA-IR, TNF-α, IL-6and liver contents of TNF-α, IL-6, MDA than those in normal group (P<0.01),as well as an decrease in liver contents of GSH and the activity of SOD (P<0.05).Compared with model group, a remarkable reduction (P<0.05) were observed in serumALT, AST, TG, TC, FFA, HOMA-IR, TNF-α, IL-6and liver contents of TNF-α, IL-6,MDA in treatment group; the degrees of hepatic steatosis and inflammation weresignificantly alleviated; the contents of GSH and the activity of SOD in liver were higher(P<0.05). The protein and mRNA expressions of liver HO-1and the expression of Nrf2inliver cell nucleus were significantly higher in treatment group than those in normal groupand model group (P<0.01).Conclusions: Curcumin can prevent and treat NASH via reducing lipid, improving IR,anti-inflammatory and anti-oxidant, which may be related to its induction of HO-1andactivation of Nrf2.