Intrahepatic cholestasis is a common pathological condition of several types of liver disorders. In this study, it aimed to investigate the hepatoprotective effect of emodin against cholestasis liver injury induced by α-naphthylisothiocyanate (ANIT) in rats.

Forty SD rats were randomly divided into control group, model group, emodin group with ANIT treatment and emodin group without ANIT treatment. Emodin group with and without ANIT treatment groups were intragastrically administrated emodin (40 mg·kg^-1·d^-1) for 7 days, and the control group and the model group were fed by sodium carboxymethylcellulose. On the 5th day after administration and fasting 4 h, the model group and the emodin group with ANIT treatment were given ANIT (50 mg·kg^-1·d^-1) to establish the intrahepatic cholestasis model, and the other two groups were fed by olive oil. At 48 h after the model establishment, the specimens were collected. The liver histopathological changes were observed by hematoxylin-eosin (HE). The levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), total bilirubin (TBiL), direct bilirubin (DBiL) and total bile acid (TBA) in serum were determined by colorimetric quantitative method. The levels of malondialdehyde (MDA), myeloperoxidase (MPO), tumor necrosis factor-α(TNF-α), interleukin-6 (IL-6) and interleukin-1β(IL-1β) of liver tissue were measured by ELISA. Quantitative fluorescent PCR was used to detect the expression levels of tumor necrosis factor-α-induced protein 8-like 2 (TIPE2), Toll-like receptor 4 (TLR4) and nuclear factor kappa B (NF-κB) mRNA. Western blot was used to evaluate the changes in the protein levels of TIPE2, TLR4 and NF-κB.

Compared with those in the control group, the concentrations of ALT, AST, GGT, TBiL, DBiL and TBA, the contents of MDA, MPO, TNF-α, IL-6 and IL-1β were significantly increased in the model group (P<0.01). The mRNA and protein expressions of TIPE2 were down-regulated (P<0.01), while the expressions of TLR4 and NF-κB were increased (P<0.01). Compared with the model group, emodin treatment could reduce the levels of ALT, AST, GGT, TBiL, DBiL and TBA (P<0.01), decrease the concentrations of MDA, MPO, TNF-α, IL-6 and IL-1β(P<0.01), increase the expression of TIPE2 (P<0.01), meanwhile significantly inhibit the expressions of TLR4 and NF-κB (P<0.05, P<0.01).

Emodin has a protective effect against intrahepatic cholestasis in the rats through up-regulating the expression of TIPE2 and inhibition of the TLR4/NF-κB pathway.