Abstract: To investigate the hepatoprotective activities of Corynoline in the mice model of carbon tetrachloride (CCl₄)-induced liver toxicity.In addition,attempts were made to elucidate the possible mechanism of action.Hepatotoxicity was induced in Kunming mice by a intraperitoneal injection (i.p.) of CCl₄,10 mL/kg body weight,diluted with corn oil at a ratio of 1:500.The corynoline (COR) was administered once a day for 7 days (i.p.) as pretreatment at 10 mg/kg·day.The levels of C-reactive protein (CRP) and tumor necrosis factor-α (TNF-α) were analyzed to determine the inflammation status.The levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were analyzed by ELISA.Liver ultrastructure was observed via optical microscopy.The protein expression degrees of peroxisome proliferator-activated receptor gamma (PPARγ) and nuclear factor-k gene binding (NF-κB) were assayed by Western blot.CCl₄-induced hepatotoxicity was manifested by an increase in the levels of ALT,AST,CRP and TNF-ɑ.The histopathological examination of liver sections revealed necrosis and inflammatory reactions.The pretreatment with COR decreased levels of ALT,AST,CRP and TNF-ɑ,decreased the protein expression degrees of NFκB,and the protein expression degrees of PPARγ,and normalized the hepatic histo-architecture.This study supported the use of COR against hepatotoxicity,and the hepatoprotective effect was mainly through PPARγ and NF-κB signaling passway.

Key words: Corynoline, carbon tetrachloride, anti-inflammatory, hepatotoxicity, peroxisome proliferator-activated receptor