PMID- 37391008 OWN - NLM STAT- MEDLINE DCOM- 20230724 LR - 20230724 IS - 1879-0712 (Electronic) IS - 0014-2999 (Linking) VI - 954 DP - 2023 Sep 5 TI - Eriocalyxin B ameliorated Crohn's disease-like colitis by restricting M1 macrophage polarization through JAK2/STAT1 signalling. PG - 175876 LID - S0014-2999(23)00387-4 [pii] LID - 10.1016/j.ejphar.2023.175876 [doi] AB - 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-1beta, TNF-alpha 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. CI - Copyright (c) 2023 The Authors. Published by Elsevier B.V. All rights reserved. FAU - Cheng, Yang AU - Cheng Y AD - Department of Blood Transfusion, First Affiliated Hospital of Bengbu Medical College, Bengbu, China. FAU - Li, Jing AU - Li J AD - 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. FAU - Wang, Lian AU - Wang L AD - 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. FAU - Wu, Xiaopei AU - Wu X AD - Bengbu Medical College, Bengbu, Anhui, China. FAU - Li, Yuetong AU - Li Y AD - Bengbu Medical College, Bengbu, Anhui, China. FAU - Xu, Mengyu AU - Xu M AD - Bengbu Medical College, Bengbu, Anhui, China. FAU - Li, Qingqing AU - Li Q AD - 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. FAU - Huang, Ju AU - Huang J AD - 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. FAU - Zhao, Tianhao AU - Zhao T AD - Department of Gastroenterology, First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui, China. FAU - Yang, Zi AU - Yang Z AD - Department of Gastrointestinal Surgery, First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui, China. FAU - Zhang, Hao AU - Zhang H AD - Department of Gastrointestinal Surgery, First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui, China. FAU - Zuo, Lugen AU - Zuo L AD - 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. FAU - Zhang, Xiaofeng AU - Zhang X AD - 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. FAU - Geng, Zhijun AU - Geng Z AD - 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. FAU - Wang, Yueyue AU - Wang Y AD - 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. FAU - Song, Xue AU - Song X AD - 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. FAU - Zhang, Jun AU - Zhang J AD - Department of Blood Transfusion, First Affiliated Hospital of Bengbu Medical College, Bengbu, China. Electronic address: 13909652118@163.com. LA - eng PT - Journal Article DEP - 20230628 PL - Netherlands TA - Eur J Pharmacol JT - European journal of pharmacology JID - 1254354 RN - 0 (eriocalyxin B) RN - EC 2.7.10.2 (Janus Kinase 2) SB - IM MH - Animals MH - Mice MH - *Crohn Disease/drug therapy MH - Janus Kinase 2/metabolism MH - Molecular Docking Simulation MH - *Colitis/chemically induced/drug therapy/metabolism MH - Macrophages OTO - NOTNLM OT - Colitis OT - Crohn's disease OT - Eriocalyxin B OT - JAK2/STAT1 OT - macrophage COIS- Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2023/07/01 11:41 MHDA- 2023/07/24 06:43 CRDT- 2023/06/30 19:15 PHST- 2023/01/28 00:00 [received] PHST- 2023/06/20 00:00 [revised] PHST- 2023/06/21 00:00 [accepted] PHST- 2023/07/24 06:43 [medline] PHST- 2023/07/01 11:41 [pubmed] PHST- 2023/06/30 19:15 [entrez] AID - S0014-2999(23)00387-4 [pii] AID - 10.1016/j.ejphar.2023.175876 [doi] PST - ppublish SO - Eur J Pharmacol. 2023 Sep 5;954:175876. doi: 10.1016/j.ejphar.2023.175876. Epub 2023 Jun 28.