2. Academic Validation
  3. Eriocalyxin B ameliorated Crohn's disease-like colitis by restricting M1 macrophage polarization through JAK2/STAT1 signalling

Eriocalyxin B ameliorated Crohn's disease-like colitis by restricting M1 macrophage polarization through JAK2/STAT1 signalling

  • Eur J Pharmacol. 2023 Jun 28;954:175876. doi: 10.1016/j.ejphar.2023.175876.
Yang Cheng 1,  Jing Li 2,  Lian Wang 3,  Xiaopei Wu 4,  Yuetong Li 4,  Mengyu Xu 4,  Qingqing Li 2,  Ju Huang 2,  Tianhao Zhao 5,  Zi Yang 6,  Hao Zhang 6,  Lugen Zuo 3,  Xiaofeng Zhang 7,  Zhijun Geng 7,  Yueyue Wang 2,  Xue Song 8,  Jun Zhang 9
Affiliations

Affiliations

  • 1 Department of Blood Transfusion, First Affiliated Hospital of Bengbu Medical College, Bengbu, China.
  • 2 Department of Clinical Laboratory, First Affiliated Hospital of Bengbu Medical College, Bengbu, China; Inflammatory Bowel Disease Research Center, First Affiliated Hospital of Bengbu Medical College, Bengbu, China.
  • 3 Inflammatory Bowel Disease Research Center, First Affiliated Hospital of Bengbu Medical College, Bengbu, China; Department of Gastrointestinal Surgery, First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui, China.
  • 4 Bengbu Medical College, Bengbu, Anhui, China.
  • 5 Department of Gastroenterology, First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui, China.
  • 6 Department of Gastrointestinal Surgery, First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui, China.
  • 7 Inflammatory Bowel Disease Research Center, First Affiliated Hospital of Bengbu Medical College, Bengbu, China; Department of Central Laboratory, First Affiliated Hospital of Bengbu Medical College, Bengbu, China.
  • 8 Inflammatory Bowel Disease Research Center, First Affiliated Hospital of Bengbu Medical College, Bengbu, China; Department of Central Laboratory, First Affiliated Hospital of Bengbu Medical College, Bengbu, China. Electronic address: songxue0214@bbmc.edu.cn.
  • 9 Department of Blood Transfusion, First Affiliated Hospital of Bengbu Medical College, Bengbu, China. Electronic address: 13909652118@163.com.
PMID: 37391008 DOI: 10.1016/j.ejphar.2023.175876
Abstract

Background and aims: M1 polarization of macrophages in the intestine is an important maintenance factor of the inflammatory response in Crohn's disease (CD). Eriocalyxin B (EriB) is a natural medicine that antagonizes inflammation. Our study aimed to determine the effects of EriB on CD-like colitis in mice, as well as the possible mechanism.

Methods: 2,4,6-trinitrobenzene sulfonic acid (TNBS) mice and IL-10-/- mice were used as CD animal models, and the therapeutic effect of EriB on CD-like colitis in mice was addressed by the disease activity index (DAI) score, weight change, histological analysis and flow cytometry assay. To assess the direct role of EriB in regulating macrophage polarization, bone marrow-derived macrophages (BMDMs) were induced to M1 or M2 polarization separately. Molecular docking simulations and blocking experiments were performed to explore the potential mechanisms by which EriB regulates the macrophage polarization.

Results: EriB treatment reduced body weight loss, DAI score and histological score, demonstrating the improvement of colitis symptoms in mice. In vivo and in vitro experiments both showed that EriB decreased the M1 polarization of macrophages, and suppressed the release of proinflammatory cytokines (IL-1β, TNF-α and IL-6) in mouse colons and BMDMs. The activation of Janus kinase 2/signal transducer and activator of transcription 1 (JAK2/STAT1) signals could be inhibited by EriB, which may be related to the regulation of EriB on M1 polarization.

Conclusions: EriB inhibits the M1 polarization of macrophages by attenuating the JAK2/STAT1 pathway, which partially explains the potential mechanism by which EriB ameliorates colitis in mice, and provides a new regimen for the clinical treatment of CD.

Keywords

Colitis; Crohn's disease; Eriocalyxin B; JAK2/STAT1; macrophage.

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