Efficacy Of Cigu Xiaozhi Pill () On Non-Alcoholic Steato-Hepatitis-Associated Lipoapoptosis Through Stress-Activated C-Jun N-Terminal Kinase Signalling Pathway

Yanhua Ma,Tao Han, Shaojun Yang, Chengzu Yu,Xia Shi,Yan Wu

JOURNAL OF TRADITIONAL CHINESE MEDICINE(2021)

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摘要
OBJECTIVE: To investigate the efficacy of Cigu Xiaozhi pill (CGXZ) on non-alcoholic steatohepatitis (NASH)-associated lipoapoptosis through the stress-activated c-Jun N-terminal kinase (JNK)/ stress-activated protein kinase signalling pathway.METHODS: Sixty male Sprague-Dawley rats were randomly divided into the following groups (10 rats each): blank control, model, low-dose CGXZ, medium-dose CGXZ, high-dose CGXZ, and positive control (treated with SP600125, a JNK inhibitor). The NASH model was established and the histomor-phological characteristics of haematoxylin and eosin-stained liver tissues were examined under a light microscope. Cell apoptosis in liver tissues was assessed via terminal deoxynucleotidyl transferase dUTP nick-end labelling assay. In addition, the mRNA and protein expression levels of p-JNK, p-c-Jun, caspase-8, Fas, and Fas-L were determined via fluorescence-based quantitative real-time PCR, immunohistochemical and Western blot assays.RESULTS: Histopathological examination of the liver showed that the model rats had moderate-to-severe steatosis with infiltration of inflammatory cells as well as significantly higher expression levels of the p-JNK, p-c-Jun, caspase-8, Fas, and Fas-L proteins, compared with those in the blank control group (P < 0.01). Hepatic lobules of the rats in the treatment groups showed significantly reduced vacuolar degeneration and steatosis as well as alleviated inflammatory cell infiltration. The high and medium-dose CGXZ groups exhibited significantly lower mRNA and protein expression levels of p-JNK, p-c-Jun, caspase-8, Fas, and Fas-L, compared with those in the model group (P < 0.05 or P < 0.01).CONCLUSION: CGXZ pill inhibited the onset of hepatocyte apoptosis by regulating the expression of p-JNK, p-c-Jun, caspase-8, Fas, and Fas-L, thereby exerting therapeutic effects against NASH. (C) 2021 JTCM. All rights reserved.
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关键词
Non-alcoholic fatty liver disease, JNK mitogen-activated protein kinases, apoptosis, stress-activated signaling pathway, Cigu Xiaozhi pill
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