结直肠癌（CRC）由于其高发病率和死亡率而日益成为关注的焦点，寻找有效且毒副作用较小的抗炎性肠病活性物质已成为针对CRC药物研发的热门话题。据报道，从巴戟天根中提取的单醣龙胆苷可以改善小鼠Dextran Sodium Sulfate（DSS）诱导的溃疡性结肠炎，但其对CRC治疗的疗效和机制尚待研究。在本研究中，我们首先使用分子对接、BLI、CESTA和DARTS方法检测单醣龙胆苷是否靶向维生素D受体（VDR）蛋白。此外，我们还使用肿瘤细胞条件培养和四种巨噬细胞极化模型，通过RT-PCR、IF和western blot研究单醣龙胆苷对四种巨噬细胞极化的调节作用。此外，我们还使用敲除动物进一步验证了单醣龙胆苷治疗Azoxymethane（AOM）/DSS诱导结肠炎相关癌（CAC）的靶点作用。同时，我们通过检测JAK/STAT1相关基因和蛋白进一步探索了单醣龙胆苷调节极化的作用机制。分子对接和生物膜干扰技术显示单醣龙胆苷结合到VDR，CESTA和DARTS的进一步结果则表明VDR蛋白是单醣龙胆苷的靶点。此外，在肿瘤细胞条件培养或LPS+IFN-γ诱导的RAW264.7细胞中，单醣龙胆苷干预后减少了VDR向细胞核的迁移，上调了JAK1/STAT1信号通路蛋白，并使巨噬细胞向M1型极化。敲除正常VDR或髓系VDR的动物模型证实，单醣龙胆苷干预后肠组织中JAK1水平增加，巨噬细胞向M1型极化，CAC伴癌灶得到改善。综上所述，本研究得出结论，单醣龙胆苷通过VDR/JAK1/STAT1调节巨噬细胞极化抑制了结肠炎相关癌。版权©2023 Elsevier B.V.保留所有权限。

Colorectal cancer (CRC) is a growing concern due to its high morbidity and mortality, and the search for effective and less toxic active substances against inflammatory bowel diseases has been a hot topic in the research and development of drugs against CRC. It is reported that monotropein isolated from the roots of Morinda officinalis, can improve Dextran Sodium Sulfate (DSS)-induced ulcerative colitis in mice, but its therapeutic effects and mechanisms for CRC treatment are still to be investigated. In the present study, we first used molecular docking, BLI, CESTA, and DARTS methods to detest whether monotropein targets VDR proteins. In addition, we used tumor cell conditioned co-culture and four models of macrophage polarisation to investigate the regulation of four macrophage polarisations by monotropein using RT-PCR, IF and western blot. Furthermore, we further validated the target of action of monotropein for the treatment of Azoxymethane (AOM)/DSS induced colitis associated cancer (CAC) using knockout animals. Meanwhile, we further explored the mechanism of action of monotropein in regulating polarisation by detecting JAK/STAT1-related genes and proteins. Molecular docking and biofilm interference techniques showed that monotropein bound to the VDR, and additional results from CESTA and DARTS suggested that VDR proteins are targets of monotropein. Furthermore, in tumor cell conditioned co-cultures or LPS + IFN-γ induced RAW264.7 cells, VDR translocation to the nucleus was reduced, JAK1/STAT1 signaling pathway proteins were up-regulated, and macrophages were polarised towards the M1-type after monotropein intervention. Animal models in which normal VDR or myeloid VDR was knocked out confirmed that JAK1 levels in intestinal tissues were increased after monotropein intervention, macrophages were polarised towards the M1 type, and CAC paracarcinomas were ameliorated. Taken together, the present study concluded that monotropein inhibited colitis-associated cancers through macrophage polarisation regulated by VDR/JAK1/STAT1.Copyright © 2023 Elsevier B.V. All rights reserved.