{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T01:15:18Z","timestamp":1792199718171,"version":"4.4.0"},"reference-count":47,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2025,10,19]],"date-time":"2025-10-19T00:00:00Z","timestamp":1760832000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Key Research and Development Program of China","award":["2023YFF0724803"],"award-info":[{"award-number":["2023YFF0724803"]}]},{"name":"Major Science and Technology Project in the Autonomous Region","award":["2023A02010-3"],"award-info":[{"award-number":["2023A02010-3"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82074103"],"award-info":[{"award-number":["82074103"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Fundamental Research Funds","award":["ZXKT25004"],"award-info":[{"award-number":["ZXKT25004"]}]},{"name":"Space Medical Experiment Project of CMSP","award":["HYZHXMX2003"],"award-info":[{"award-number":["HYZHXMX2003"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Berberine (BBR), a benzylisoquinoline alkaloid isolated from Chinese herb Coptis chinensis, has been widely used clinically to treat intestinal infectious diseases. Recently, it has been found to have multiple pharmacological effects, including anti-inflammatory activity and immune effects in inflammatory bowel disease (IBD). However, its exact targets remain to be elucidated. In this study, we used a mouse intestinal organoid\u2013macrophage co-culture model to investigate the anti-inflammatory effects and immune effects of BBR. Our findings demonstrated that lipopolysaccharide (LPS) induced more robust inflammatory responses and epithelium damage in the co-culture system compared to the organoid alone. BBR effectively attenuated inflammation and restored epithelial barrier integrity by suppressing M1 macrophage polarisation and infiltration, alongside upregulating the expression and organisation of tight junction protein zonula occludens-1 (ZO-1). RNA sequencing and proteomic analysis revealed that BBR disrupted organoid\u2013macrophage interaction by inhibiting chemokine (e.g., C-X-C motif chemokine ligand 1 (CXCL1) and macrophage migration inhibitory factor (MIF)) release from epithelial cells, thereby reducing macrophage recruitment. Collectively, our study establishes the organoid\u2013macrophage co-culture system as a more physiologically relevant model for studying epithelial\u2013immune interactions and elucidates the multi-target mechanism of BBR, which concurrently modulates epithelial cells, macrophages, and their crosstalk. These findings lay the foundation for further exploration of the therapeutic potential of BBR in inflammatory bowel disease and the development of targeted therapies that regulate cell interactions.<\/jats:p>","DOI":"10.3390\/ijms262010161","type":"journal-article","created":{"date-parts":[[2025,10,20]],"date-time":"2025-10-20T08:18:54Z","timestamp":1760948334000},"page":"10161","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Berberine Alleviates Intestinal Inflammation by Disrupting Pathological Macrophage\u2013Epithelial Crosstalk in Macrophage\u2013Organoid Co-Culture Model"],"prefix":"10.3390","volume":"26","author":[{"given":"Yuncong","family":"Han","sequence":"first","affiliation":[{"name":"College of Chemistry and Life Science, Beijing University of Technology, Beijing 100124, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengting","family":"Li","sequence":"additional","affiliation":[{"name":"Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tian","family":"Chen","sequence":"additional","affiliation":[{"name":"College of Chemistry and Life Science, Beijing University of Technology, Beijing 100124, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Chemistry and Life Science, Beijing University of Technology, Beijing 100124, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Zhou","sequence":"additional","affiliation":[{"name":"College of Chemistry and Life Science, Beijing University of Technology, Beijing 100124, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tunan","family":"Zhou","sequence":"additional","affiliation":[{"name":"College of Chemistry and Life Science, Beijing University of Technology, Beijing 100124, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Runqing","family":"Jia","sequence":"additional","affiliation":[{"name":"College of Chemistry and Life Science, Beijing University of Technology, Beijing 100124, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Chen","sequence":"additional","affiliation":[{"name":"Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1196-879X","authenticated-orcid":false,"given":"Qin","family":"Hu","sequence":"additional","affiliation":[{"name":"College of Chemistry and Life Science, Beijing University of Technology, Beijing 100124, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"504","DOI":"10.1002\/ptr.6252","article-title":"Berberine and Barberry (Berberis vulgaris): A Clinical Review","volume":"33","author":"Imenshahidi","year":"2019","journal-title":"Phytother. 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