Epimedokoreanin B induces pyroptosis in HepaRG cells through NLRP1/caspase-1/GSDMD signaling pathway
- VernacularTitle:朝藿素B通过NLRP1/caspase-1/GSDMD信号通路诱导HepaRG细胞焦亡
- Author:
Yu-tong DONG
1
;
Hao-ran HU-YAN
;
Li-zhen QIU
;
Chao MA
;
Shao-xia WANG
;
Kun ZHOU
Author Information
- Publication Type:Journal Article
- Keywords: epimedokoreanin B; pyroptosis; endo-plasmic reticulum stress; HepaRG cells; NLRP1; GS-DMD
- From: Chinese Pharmacological Bulletin 2025;41(11):2053-2057
- CountryChina
- Language:Chinese
- Abstract: Aim To explore the role and mechanism of epimedokoreanin B(EKB)in HepaRG cell pyroptosis through endoplasmic reticulum stress and NLRP1-me-diated pyroptosis pathway.Methods The effect of EKB on the viability of HepaRG cells at different con-centrations was determined by MTT assay,and the cell growth status was recorded by Incucyte.Four groups of HepaRG cells were set up.The control group was cul-tured with complete medium for 24 h;the drug admin-istration group was cultured with three concentration gradients of 6.25,12.5 and 25 μmol·L-1 of EKB for 24 h.Western blot was used to detect the expression levels of endoplasmic reticulum stress-related proteins and pyroptosis-related proteins in the cells of each group.Results HepaRG cells showed cytotoxicity at a concentration of 6.25 μmol·L-1 for 24 h,and the half maximal inhibitory concentration(IC50)was 12.41 μmol·L-1.Incucyte recordings of the cell growth status showed that the cells in the control group were in good growth status,and the vesicular pyropto-sis cells appeared in the different concentrations of EKB and the cells swelled and ruptured after 24 h.Western blot showed that the protein expression levels of endoplasmic reticulum stress-related proteins pERK,eIF-2α,ATF-4,GRP78,and CHOP significantly in-creased in HepaRG cells at 25 μmol·L-1 of EKB compared with the control group.The proteins of the classical pathway of cellular pyroptosis mediated by NLRP1,caspase-1,cleaved caspase-1,GSDMD,GS-DMD-N significantly increased in HepaRG cells.Con-clusion EKB administration induces HepaRG cell py-roptosis,and EKB activates HepaRG cells to undergo endoplasmic reticulum stress and activates the NLRP1/caspase-1/GSDMD-mediated pyroptosis pathway.
