Ecliptasaponin A ameliorates DSS-induced colitis in mice by suppressing M1 macrophage polarization via inhibiting the JAK2/STAT3 pathway.
10.12122/j.issn.1673-4254.2025.06.19
- Author:
Minzhu NIU
1
;
Lixia YIN
2
;
Tong QIAO
3
;
Lin YIN
2
;
Keni ZHANG
2
;
Jianguo HU
1
;
Chuanwang SONG
3
;
Zhijun GENG
1
;
Jing LI
1
Author Information
1. Anhui Provincial Key Laboratory of Basic and Translational Research of Inflammation-related Diseases, First Affiliated Hospital of Bengbu Medical University, Bengbu 233004, China.
2. Clinical Laboratory, First Affiliated Hospital of Bengbu Medical University, Bengbu 233004, China.
3. Department of Immunology, School of Laboratory Medicine, Bengbu Medical University, Bengbu 233030, China.
- Publication Type:Journal Article
- Keywords:
JAK2/STAT3;
ecliptasaponin A;
inflammatory bowel disease;
intestinal barrier;
macrophage polarization
- MeSH:
Animals;
Mice;
Janus Kinase 2/metabolism*;
STAT3 Transcription Factor/metabolism*;
Mice, Inbred C57BL;
Male;
Dextran Sulfate;
Macrophages/cytology*;
Colitis/metabolism*;
Saponins/pharmacology*;
Signal Transduction/drug effects*;
RAW 264.7 Cells;
Triterpenes/pharmacology*;
Interleukin-6/metabolism*
- From:
Journal of Southern Medical University
2025;45(6):1297-1306
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVES:To investigate the effect of ecliptasaponin A (ESA) for alleviating dextran sulfate sodium (DSS)-induced inflammatory bowel disease (IBD) in mice and the underlying mechanism.
METHODS:Twenty-four male C57BL/6 mice (8-10 weeks old) were equally randomized into control group, DSS-induced IBD model group, and DSS+ESA (50 mg/kg) treatment group. Disease activity index (DAI), colon length and spleen index of the mice were measured, and intestinal pathology was examined with HE staining. The expressions of inflammatory mediators (TNF-α, IL-6, and iNOS) in the colon mucosa were detected using ELISA and RT-qPCR, and intestinal barrier integrity was assessed using AB-PAS staining and by detecting ZO-1 and claudin-1 expressions using immunofluorescence staining and Western blotting. In cultured RAW264.7 macrophages, the effects of treatment with 50 μmol/L ESA, alone or in combination with 20 μmol/L RO8191 (a JAK2/STAT3 pathway activator), on M1 polarization of the cells induced by LPS and IFN-γ stimulation and expressions of JAK2/STAT3 pathway proteins were analyzed using flow cytometry and Western blotting.
RESULTS:In the mouse models of DSS-induced IBD, ESA treatment significantly alleviated body weight loss and colon shortening, reduced DAI, spleen index and histological scores, and ameliorated inflammatory cell infiltration in the colon tissue. ESA treatment also suppressed TNF‑α, IL-6 and iNOS expressions, protected the goblet cells and the integrity of the mucus and mechanical barriers, and upregulated the expressions of ZO-1 and claudin-1. ESA treatment obviously decreased CD86+ M1 polarization in the mesenteric lymph nodes of IBD mice and in LPS and IFN-γ-induced RAW264.7 cells, and significantly reduced p-JAK2 and p-STAT3 expressions in both the mouse models and RAW264.7 cells. Treatment with RO8191 caused reactivation of JAK2/STAT3 and strongly attenuated the inhibitory effect of ESA on CD86+ polarization in RAW264.7 cells.
CONCLUSIONS:ESA alleviates DSS-induced colitis in mice by suppressing JAK2/STAT3-mediated M1 macrophage polarization and mitigating inflammation-driven intestinal barrier damage.
