PMID- 36197455 OWN - NLM STAT- MEDLINE DCOM- 20221007 LR - 20221028 IS - 1530-6860 (Electronic) IS - 0892-6638 (Linking) VI - 36 IP - 11 DP - 2022 Nov TI - Vindoline ameliorates intestinal barrier damage in Crohn's disease mice through MAPK signaling pathway. PG - e22589 LID - 10.1096/fj.202200234RR [doi] AB - Intestinal inflammation and intestinal barrier damage are important pathological changes in Crohn's disease (CD). Vindoline is a natural monomer with anti-inflammatory effects. We employed CD model mice to explore the effect of Vindoline on CD-like colitis and the possible mechanism. Il-10-deficient (Il-10(-/-) ) mice and wild-type (WT) mice (both aged 15 weeks, male) were used to explore the effect of Vindoline on colitis and intestinal barrier damage, as well as macrophage-mediated inflammation. Bone-marrow-derived macrophages (BMDMs) and colonic organoids from mice were used to explore the inhibitory effect of Vindoline on macrophage-mediated inflammation and the protective effect on inflammation-induced intestinal barrier damage as well as the possible mechanism. We found that Vindoline significantly ameliorated colitis in CD mice, as evidenced by increased weight change and colon length and decreased the colon macroscopic injury score, histological inflammatory score, and the expression of pro-inflammatory mediators. Vindoline also protected against intestinal barrier damage in CD mice. Furthermore, Vindoline inhibited macrophage-mediated inflammation and protected against inflammation-induced intestinal barrier damage in the coculture system. In addition, Vindoline ameliorated colitis in CD mice by protecting against inflammation-induced intestinal barrier damage, which may be caused by inhibition of MAPK signaling pathway. This protective effect suggests that Vindoline has potential value for clinical application in the treatment of CD. CI - (c) 2022 The Authors. The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology. FAU - Zhang, Xiaofeng AU - Zhang X AUID- ORCID: 0000-0001-8338-8335 AD - Department of Central Laboratory, The First Affiliated Hospital of Bengbu Medical College, Bengbu, China. AD - Anhui Key Laboratory of Tissue Transplantation, Bengbu Medical College, Bengbu, China. FAU - Zuo, Lugen AU - Zuo L AD - Department of Central Laboratory, The First Affiliated Hospital of Bengbu Medical College, Bengbu, China. AD - Department of Gastrointestinal Surgery, The First Affiliated Hospital of Bengbu Medical College, Bengbu, China. FAU - Geng, Zhijun AU - Geng Z AD - Department of Central Laboratory, The First Affiliated Hospital of Bengbu Medical College, Bengbu, China. AD - Anhui Key Laboratory of Tissue Transplantation, Bengbu Medical College, Bengbu, China. FAU - Song, Xue AU - Song X AD - Department of Central Laboratory, The First Affiliated Hospital of Bengbu Medical College, Bengbu, China. AD - Anhui Key Laboratory of Tissue Transplantation, Bengbu Medical College, Bengbu, China. FAU - Li, Jing AU - Li J AD - Department of Central Laboratory, The First Affiliated Hospital of Bengbu Medical College, Bengbu, China. AD - Department of Clinical Laboratory, The First Affiliated Hospital of Bengbu Medical College, Bengbu, China. FAU - Ge, Sitang AU - Ge S AD - Department of Central Laboratory, The First Affiliated Hospital of Bengbu Medical College, Bengbu, China. AD - Department of Gastrointestinal Surgery, The First Affiliated Hospital of Bengbu Medical College, Bengbu, China. FAU - Jiang, Yifan AU - Jiang Y AD - Anhui Key Laboratory of Tissue Transplantation, Bengbu Medical College, Bengbu, China. FAU - Yang, Zi AU - Yang Z AD - Department of Central Laboratory, The First Affiliated Hospital of Bengbu Medical College, Bengbu, China. FAU - Liu, Guangyong AU - Liu G AD - Anhui Key Laboratory of Tissue Transplantation, Bengbu Medical College, Bengbu, China. FAU - Zhao, Yajing AU - Zhao Y AD - Anhui Key Laboratory of Tissue Transplantation, Bengbu Medical College, Bengbu, China. FAU - Zhao, Hao AU - Zhao H AD - Department of Central Laboratory, The First Affiliated Hospital of Bengbu Medical College, Bengbu, China. FAU - Yu, Liang AU - Yu L AD - Department of Central Laboratory, The First Affiliated Hospital of Bengbu Medical College, Bengbu, China. FAU - Hu, Jianguo AU - Hu J AUID- ORCID: 0000-0003-0207-9536 AD - Anhui Key Laboratory of Tissue Transplantation, Bengbu Medical College, Bengbu, China. AD - Department of Clinical Laboratory, The First Affiliated Hospital of Bengbu Medical College, Bengbu, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - FASEB J JT - FASEB journal : official publication of the Federation of American Societies for Experimental Biology JID - 8804484 RN - 0 (Anti-Inflammatory Agents) RN - 0 (Inflammation Mediators) RN - 130068-27-8 (Interleukin-10) RN - 571PJ1LW03 (vindoline) RN - 5V9KLZ54CY (Vinblastine) RN - 9042-14-2 (Dextran Sulfate) SB - IM MH - Animals MH - Anti-Inflammatory Agents/pharmacology MH - *Colitis/chemically induced/drug therapy/pathology MH - Colon/metabolism MH - *Crohn Disease/drug therapy/pathology MH - Dextran Sulfate/pharmacology MH - Disease Models, Animal MH - Inflammation/pathology MH - Inflammation Mediators/pharmacology MH - Interleukin-10/metabolism MH - Intestinal Mucosa/metabolism MH - Male MH - Mice MH - Mice, Inbred C57BL MH - Signal Transduction MH - Vinblastine/analogs & derivatives OTO - NOTNLM OT - Crohn's disease OT - colitis OT - intestinal barrier damage OT - macrophage-mediated inflammation OT - vindoline EDAT- 2022/10/06 06:00 MHDA- 2022/10/12 06:00 CRDT- 2022/10/05 11:13 PHST- 2022/08/09 00:00 [revised] PHST- 2022/02/13 00:00 [received] PHST- 2022/09/23 00:00 [accepted] PHST- 2022/10/05 11:13 [entrez] PHST- 2022/10/06 06:00 [pubmed] PHST- 2022/10/12 06:00 [medline] AID - 10.1096/fj.202200234RR [doi] PST - ppublish SO - FASEB J. 2022 Nov;36(11):e22589. doi: 10.1096/fj.202200234RR.