Berberine Alleviates Intestinal Inflammation by Disrupting Pathological Macrophage–Epithelial Crosstalk in Macrophage–Organoid Co-Culture Model

作者：Yuncong Han, Mengting Li, Tian Chen, Chen Wang, Hong Zhou, Tunan Zhou, Runqing Jia, Ying Chen, Qin Hu · 发表于：International Journal of Molecular Sciences · 年份：2025 · DOI：10.3390/ijms262010161 · 被引用次数：6 · 研究领域：Berberine and alkaloids research、Alkaloids: synthesis and pharmacology、Barrier Structure and Function Studies

, 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-macrophage 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-macrophage 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-macrophage co-culture system as a more physiologically relevant model for studying epithelial-immune 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 e...