Atractylenolide Ⅲ maintains Th17/Treg balance by inhibiting STAT3 signaling in a mouse model of chronic inflammatory bowel disease
10.3969/j.issn.1000-4718.2024.12.018
- VernacularTitle:白术内酯Ⅲ在小鼠慢性炎性肠病模型中通过抑制STAT3信号维持Th17/Treg平衡
- Author:
Ruikang FANG
1
;
Dongna ZHANG
;
Jingjing LI
;
Yilong ZHU
;
Haiyang ZHANG
;
Xu GAO
;
Guangze ZHU
;
Yiquan LI
;
Jicheng HAN
Author Information
1. 长春中医药大学中西医结合学院吉林省传染性疾病中医药防治重点实验室,吉林 长春 130117;延边大学农学院,吉林 延边 133000
- Publication Type:Journal Article
- Keywords:
atractylenolide Ⅲ;
inflammatory bowel disease;
Th17/Treg balance;
STAT3 signaling pathway
- From:
Chinese Journal of Pathophysiology
2024;40(12):2336-2342
- CountryChina
- Language:Chinese
-
Abstract:
AIM:To investigate the potential of atractylenolide Ⅲ(AⅢ)in mitigating dextran sulfate sodium(DSS)-induced injury in a mouse model of chronic inflammatory bowel disease(IBD),and to explore the mechanisms in-volved,particularly the modulation of signal transducer and activator of transcription 3(STAT3)signaling,which plays a crucial role in the homeostasis of T helper 17(Th17)and regulatory T(Treg)cells.METHODS:A mouse model of DSS-induced chronic IBD was established,and the mice were divided into 4 groups:control,model(DSS),high-dose(50 mg/kg)AⅢ,and low-dose(30 mg/kg)AⅢ.The disease activity index(DAI)was utilized to assess disease severity.Histo-pathological damage in the colons of IBD mice was evaluated by hematoxylin-eosin(HE)staining.The protein levels of phosphorylated STAT3,occludin and zonula occludens-1(ZO-1)were analyzed using immunohistochemical staining and Western blot.Flow cytometry was employed to examine the differentiation of splenic lymphocytes into Th17/Treg cells.RESULTS:Both DAI assessments and HE staining indicated that AⅢ significantly alleviated inflammatory injury in mice with DSS-induced chronic IBD.Immunohistochemical analysis demonstrated that AⅢ enhanced the expression of ZO-1 and occludin in colonic tissues.Flow cytometry results revealed that AⅢ helped maintain the balance between splenic Th17 and Treg cells.Furthermore,immunohistochemical staining and Western blot showed that AⅢ inhibited the phos-phorylation of STAT3.CONCLUSION:Treatment with AⅢ effectively reduced inflammatory injury in a mouse model of chronic IBD by preserving Th17/Treg homeostasis through the inhibition of STAT3 phosphorylation.As a natural com-pound,AⅢ exhibits significant therapeutic potential for the treatment of chronic IBD.
