Saikosaponin-b2 alleviates CCL4-induced acute liver injury in mice by inhibiting endoplasmic reticulum stress signal pathway / 中国药理学与毒理学杂志

ABSTRACT

OBJECTIVE To investigate the protective effect of saikosaponin-b2 (SS-b2) on acute liver injury induced by carbon tetrachloride (CCI4) and its inhibition on endoplasmic reticulum stress pathway in mice. METHODS Sixty male BALB/c mice were randomly divided into normal control, model, SS-b2 (5, 10 and 20 mg·kg-1) and silymarin (10 mg·kg-1) groups. Mice were ig given different drugs or saline for 7 d. Two hours after the last administration, mice were IP given 5% CCI4 to induce acute liver injury, except those in normal control group. The activities of glutamic-pyruvic transaminase (GPT), glutamic-oxaloacetic transaminase (GOT) and superoxide dismutase (SOD) and the content of malondialdehyde (MDA) in mouse serum were detected by colorimetric method. Pathological changes in liver tissue were detected by HE staining. The expression levels of protein kinase R-like ER kinase (PERK), phospho-eukaryotic initiation factory 2a (p-elF2α), activating transcrIPtion factor-4(ATF4), glucose regulated protein 78 (GRP78) and CCAAT/enhancer-binding protein homologous protein (CHOP) were detected by immuno-histochemistry and Western blotting. RESULTS Compared with the normal control group, the activities of GPT and GOT and the content of MDA in mouse serum in model group were significantly increased (P<0.05, P<0.01), but the activity of SOD was significantly decreased (P<0.01). Meanwhile, the expression levels of PERK, p-elF2α, ATF4, GRP78 and CHOP in the liver tissue were significantly increased in the model group (P<0.01). Compared with the model group, SS-b2 groups significantly reduced the activity of GPT, GOT and the content of MDA in the serum of acute liver injury mice (P<0.05, P<0.01), but increased the activity of SOD (P<0.01), and the expression levels of endoplasmic reticulum stress pathway proteins mentioned above were significantly reduced (P<0.05, P<0.01). HE staining results showed that different concentrations of SS-b2 could significantly improve the swelling of hepatocytes, the dissolution of nuclei around hepatic lobules, and the arrangement disorder of hepatic cords induced by CCI4 in mice. The cell morphology was obviously improved. CONCLUSION SS-b2 has a significant protective effect on CCL-induced acute liver injury in mice. The mechanism may be related to the inhibition of oxidative stress and down-requlation of the expressions of ERS related protein.