Sanguisorbae Radix alleviates damage in ulcerative colitis model mice based on PPARG and SLC7A11/GPX4
10.3969/j.issn.1671-7856.2024.07.003
- VernacularTitle:地榆通过影响PPARG和SLC7A11/GPX4表达减轻溃疡性结肠炎小鼠损伤
- Author:
Xiaoxi YIN
1
;
Zixuan CHEN
;
Yi YUAN
;
Jingnan MA
;
Jing WANG
;
Tianyi LYU
;
Miaomiao TONG
;
Li LI
Author Information
1. 河北医科大学药学院,石家庄 050017
- Keywords:
bioinformatics;
ulcerative colitis;
ferroptosis;
core genes;
Sanguisorbae Radix
- From:
Chinese Journal of Comparative Medicine
2024;34(7):20-28
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the mechanism of Sanguisorbae Radix(SR)in the treatment of ulcerative colitis(UC).Methods Using the GSE92415 dataset from the Gene Expression Omnibus database,we analyzed differentially expressed genes and carried out weighted gene correlation network analysis and FerrDb analysis.Core genes were identified through protein-protein interaction(PPI)network and correlation analysis.UC mouse model induced by dextran sulfate sodium(DSS)was constructed and treated with SR via intragastric administration for 9 days.Disease activity index(DAI)and colon length were recorded.Pathological changes in colon tissue were observed using the HE staining.Levels of inflammatory cytokines such as tumor necrosis factor-α(TNF-α)and interleukin-6(IL-6)were detected by enzyme linked immunosorbent assay(ELISA).Lipid peroxidantion factors such as malondialdehyde(MDA)and glutathione(GSH)were detected using biochemical test kits.Protein expression levels of zonula occludens protein-1(ZO-1)tight junction protein,peroxisome proliferator-activated receptor gamma(PPARG),solute carrier family 7 member 11(SCL7A11),and glutathione peroxidase 4(GPX4)were examined by Western blot or immunofluorescence labeling.Results Nine differentially expressed genes associated with ferroptosis were screened and PPARG was identified as a key gene.Correlation analysis showed a strong correlation between PPARG and ferroptosis.Subsequently,the potential mechanism of SR in improving UC in mice was discussed according to the bioinformatics screening results.The experimental results demonstrated that SR significantly reduced the DAI,prevented colon shortening and improved intestinal mucosal barrier function in the colon.SR decreased TNF-α and IL-6 levels,MDA content and GSH levels in colon tissues.SR also enhanced the expression of PPARG,SLC7A11 and GPX4,which reversed the effect of DSS in mice with colitis.Conclusions Ferroptosis is closely related to UC.SR can inhibit ferroptosis by regulating PPARG and SCL7A11/GPX4 expression,thereby improving colon epithelial injury and dysfunction in UC mice.This provides ideas and directions for UC treatment strategies.
