Protective Effect of Silibinin on Lipopolysaccharide-Induced Endotoxemia by Inhibiting Caspase-11-Dependent Cell Pyroptosis  

作　　者：OU Jin-ying LIU Shan-hong TANG Dong-kai SHI Ling-zhu YAN Li-jun HUANG Jing-yan ZOU Li-fang QUAN Jing-yu YOU Yan-ting CHEN Yu-yao YU Lin-zhong LU Zi-bin 

机构地区：[1]Third Level Research Laboratory of State Administration of Traditional Chinese Medicine,School of Traditional Chinese Medicine,Southern Medical University,Guangzhou,510515,China [2]Guangdong Provincial Key Laboratory of Chinese Medicine Pharmaceutics,Guangzhou,510515,China [3]School of Traditional Chinese Medicine,Southern Medical University,Guangzhou,510515,China

出　　处：《Chinese Journal of Integrative Medicine》2024年第10期917-926,共10页中国结合医学杂志（英文版）

基　　金：Supported by the Guangdong Basic and Applied Basic Research Foundation(No.2023A1515011106);Science and Technology Program of Guangzhou(No.2023A04J1826)。

摘　　要：Objective:To explore the protective effect and the underlying mechanism of silibinin(SIB),one of the active compounds from Silybum marianum(L.)Gaertn in endotoxemia.Methods:Mouse peritoneal macrophage were isolated via intraperitoneally injection of BALB/c mice with thioglycolate medium.Cell viability was assessed using the cell counting kit-8,while cytotoxicity was determined through lactate dehydrogenase cytotoxicity assay.The protein expressions of interleukin(IL)-1α,IL-1β,and IL-18 were determined by enzyme-linked immunosorbent assay.Intracellular lipopolysaccharide(LPS)levels were measured by employing both the limulus amoebocyte lysate assay and flow cytometry.Additionally,proximity ligation assay was employed for the LPS and caspase-11 interaction.Mice were divided into 4 groups:the control,LPS,high-dose-SIB(100 mg/kg),and low-dose-SIB(100 mg/kg)groups(n=8).Zebrafish were divided into 4 groups:the control,LPS,high-dose-SIB(200μmol/L),and low-dose-SIB(100μmol/L)groups(n=30 for survival experiment and n=10 for gene expression analysis).The expression of caspase-11,gasdermin D(GSDMD),and N-GSDMD was determined by Western blot and the expressions of caspy2,gsdmeb,and IL-1βwere detected using quantitative real-time PCR.Histopathological observation was performed through hematoxylineosin staining,and protein levels in bronchoalveolar lavage fluid were quantified using the bicinchoninicacid protein assay.Results:SIB noticeably decreased caspase-11 and GSDMD-mediated pyroptosis and suppressed the secretion of IL-1α,IL-1β,and IL-18 induced by LPS(P<0.05).Moreover,SIB inhibited the translocation of LPS into the cytoplasm and the binding of caspase-11 and intracellular LPS(P<0.05).SIB also attenuated the expression of caspase-11 and N-terminal fragments of GSDMD,inhibited the relative cytokines,prolonged the survival time,and up-regulated the survival rate in the endotoxemia models(P<0.05).Conclusions:SIB can inhibit pyroptosis in the LPS-mediated endotoxemia model,at least in part,by inhibiting the caspase-11

关 键 词：SILIBININ caspase-11 ENDOTOXEMIA PYROPTOSIS inflammation 

分 类 号：R285.5[医药卫生—中药学]