Saikosaponin-b prevents CCl4-induced acute liver injury by down-regulating PERK/elF2α/ATF4/CHOP signal pathway in mice

[Speaker] Xing-zhi LV:1
[Co-author] Hong-Wei Wang:2, Zi-Han Gao:1, Sang-Qiang Li:1, Jian-Gang Wang:1, Rui-Fang Li:1
1:Department of Pharmacology, Medical College, Henan University of Science and Technology, China, 2:Nursing College, Henan University of Science and Technolog, China

Background:To investigate the protective effect of Saikosaponin-b (SS-b) on CCl4-induced acute liver injury and its regulation on PERK/elF2α/ ATF4/CHOP signal pathway in mice.Methods:Fifty healthy male BALB/c mice were randomly divided into 5 groups: normal group, model group, SS-b different dose group. Mice were injected subcutaneously for seven days. The acute liver injury model was induced by 5% CCl4 at 6 hours after last treatment. The liver function (ALT, AST) and oxidative stress (SOD, GSH-PX and MDA) parameters in serum were detected by colorimetric methods. Histological examination was performed using hematoxylin-eosin staining. The apoptosis was determined by Hoechst33258 staining, Caspase-9 and Caspase-3 assay. The protein expressions of GRP78, PERK, elF2α, ATF4 and CHOP in endoplasmic reticulum stress pathway were detected by immunohistochemistry and western blotting.
Results:SS-b significantly improved impaired liver function and oxidative stress in acute liver injure mice. SS-b significantly decreased the levels of ALT, AST and MDA in serum while increased serum SOD and GSH-PX in model mice. The pathological morphology of liver injury is significantly attenuated. The liver index and the spleen index of mice were significantly reduced. SS-b significantly reduced the liver cell apoptosis induced by acute liver injure. The expressions of Caspase-9 and Caspase-3 in liver tissue were decreased significantly by SS-b treatment. The expressions of GRP78, PERK, elF2α, ATF4 and CHOP in the liver tissue were significantly decreased by different dose of SS-b in acute liver injure mice.
Conclusions:SS-b has a significant protective effect on CCl4-induced acute liver injury in mice. The mechanism was related to its down-regulating on PERK/elF2α/ATF4/CHOP signal pathway in mice.

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