2. Academic Validation
  3. Complanatuside A ameliorates 2,4,6-trinitrobenzene sulfonic acid-induced colitis in mice by regulating the Th17/Treg balance via the JAK2/STAT3 signaling pathway

Complanatuside A ameliorates 2,4,6-trinitrobenzene sulfonic acid-induced colitis in mice by regulating the Th17/Treg balance via the JAK2/STAT3 signaling pathway

  • FASEB J. 2024 May 31;38(10):e23667. doi: 10.1096/fj.202301127RR.
Yueyue Wang 1 2,  Xue Song 2 3,  Yongsheng Xia 2 4,  Wenjing Zhang 1 2,  Wenjie Li 2,  Yu Wang 2,  Jing Li 1 2,  Zhijun Geng 2 3,  Xiaofeng Zhang 2 3,  Lian Wang 2 4,  Lugen Zuo 2 4,  Jianguo Hu 1 2
Affiliations

Affiliations

  • 1 Department of Clinical Laboratory, First Affiliated Hospital of Bengbu Medical University, Bengbu, Anhui, China.
  • 2 Anhui Province Key Laboratory of Basic and Translational Research of Inflammation-Related Diseases, First Affiliated Hospital of Bengbu Medical University, Bengbu, Anhui, China.
  • 3 Department of Central Laboratory, First Affiliated Hospital of Bengbu Medical University, Bengbu, Anhui, China.
  • 4 Department of Gastrointestinal Surgery, First Affiliated Hospital of Bengbu Medical University, Bengbu, Anhui, China.
PMID: 38742812 DOI: 10.1096/fj.202301127RR
Abstract

Immunity imbalance of T helper 17 (Th17)/regulatory T (Treg) cells is involved in the pathogenesis of Crohn's disease (CD). Complanatuside A (CA), a flavonol glycoside, exerts anti-inflammatory activities and our study aimed to identify its effect on TNBS-induced colitis and the possible mechanisms. We found that CA alleviated the symptoms of colitis in TNBS mice, as demonstrated by prevented weight loss and colon length shortening, as well as decreased disease activity index scores, inflammatory scores, and levels of proinflammatory factors. Flow cytometry analysis showed that CA markedly reduced the percentage of Th17 cells while increasing the percentage of Treg cells in TNBS mice. Under Th17 cell polarizing conditions, CA inhibited the differentiation of Th17 cells while the Treg cell differentiation was elevated under Treg cell polarizing conditions. Furthermore, it was observed that JAK2 interacted with CA through six hydrogen bonds via molecular docking. The phosphorylation of JAK2/STAT3 was reduced by CA, which might be correlated with the protective effect of CA on colitis. In conclusion, CA reduced the imbalance of Th17/Treg cells by inhibiting the JAK2/STAT3 signaling pathway in TNBS-induced colitis, which may provide novel strategies for CD treatment.

Keywords

Colitis; Complanatuside A; Crohn's disease; JAK2/STAT3; Th17/Treg balance.

Figures
Products