Zingiberis Rhizoma Alleviates Inflammatory Bowel Disease Through Regulating TLR4/MAPK Signaling Pathway in Ly6Chi Monocytes/Macrophages
10.13422/j.cnki.syfjx.20242435
- VernacularTitle:干姜通过TLR4/MAPK信号通路调控Ly6Chi单核/巨噬细胞改善炎症性肠病的作用机制
- Author:
Yalan LI
1
;
Chonghao ZHANG
1
;
Huachen LIU
1
;
Jialong SU
1
;
Na LI
1
;
Mengyu ZHOU
2
;
Guiying PENG
1
Author Information
1. School of Life Sciences， Beijing University of Chinese Medicine， Beijing 100029， China
2. The First Affiliated Hospital of Guangxi Medical University， Nanning 530021， China
- Publication Type:Journal Article
- Keywords:
Zingiberis Rhizoma;
inflammatory bowel disease;
monocytes/macrophages;
Toll-like receptor 4;
mitogen-activated protein kinase
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2025;31(20):66-75
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo investigate the potential mechanisms of Zingiberis Rhizoma in treating inflammatory bowel disease （IBD） by integrating network pharmacology with in vitro and in vivo experiments. MethodsTraditional Chinese Medicine Systems Pharmacology Database And Analysis Platform （TCMSP）， Traditional Chinese Medicine Integrated Database （TCMID） Database were used to obtain the active component targets of Zingiberis Rhizoma. GeneCards was used to obtain the IBD targets. DAVID was used to perform Gene Ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analyses on core targets. Cytoscape 3.10.2 was used to establish the "active component-disease target-signaling pathway" interaction network. Mice were randomly assigned to control， model， and Zingiberis Rhizoma （400 mg·kg-1） groups. An IBD model was induced via dextran sulfate sodium （DSS）. The colonic tissue was collected post-treatment to assess histology， expression of Ly6C+ monocytes/macrophages， and mRNA levels of Toll-like receptor 4 （TLR4）， and inflammatory cytokines. The effect of Zingiberis Rhizoma aqueous extract on RAW264.7 cell viability was evaluated. Furthermore， the effects of the extract at 100， 10， and 1 mg·L-1 on LPS-induced differentiation of RAW264.7 cells into Ly6Chi monocytes/macrophages， mRNA levels of TLR4 and inflammatory cytokines， and protein levels of factors in the TLR4/mitogen-activated protein kinase （MAPK） signaling pathway. ResultsA total of 241 targets were identified for Zingiberis Rhizoma and 6 787 for IBD， with 122 shared targets among Zingiberis Rhizoma， ulcerative colitis （UC）， and Crohn's disease （CD）. The enrichment analyses yielded 297 GO terms and 88 KEGG pathways. Associations were noted between Zingiberis Rhizoma's active component targets and IBD targets. In vivo experiments： Compared with the control group， the model group showed decreased body weight and disease activity index （DAI）（P<0.01）， shortened colon length， damaged mucosal epithelium with inflammatory cell infiltration， raised pathological scores （P<0.05）， increased Ly6Chi and Ly6Clo monocytes/macrophages （P<0.05）， and up-regulated mRNA levels of TLR4， TNF-α， IL-1β， and IL-6 （P<0.05） and protein levels of TLR4， phosphorylated extracellular signal-regulated protein kinase 1/2 （p-ERK1/2）， and phosphorylated p38 MAPK （p-p38 MAPK） （P<0.05）. Zingiberis Rhizoma intervention reversed these changes and reduced Ly6Chi monocytes/macrophages （P<0.01）. In vitro experiments： compared with the control， LPS increased the proportion and number of Ly6Chi monocytes/macrophages and mRNA levels of TLR4， TNF-α， IL-1β， and IL-6 （P<0.01） and enhanced the expression of TLR4， p-ERK1/2， and p-p38 MAPK （P<0.05）. Zingiberis Rhizoma reduced Ly6Chi monocytes/macrophages （P<0.05）， down-regulated the mRNA levels of inflammatory cytokines （P<0.05）， and suppressed the TLR4/MAPK pathway （P<0.05）. ConclusionZingiberis Rhizoma alleviates IBD by suppressing the TLR4/ERK/p38 MAPK signaling pathway and reducing inflammatory cytokine levels in Ly6Chi monocytes/macrophages.
