Ulcerative colitis (UC) is a chronic non-specific inflammatory disease involving the mucosa and submucosa of the rectum and colon. Lindera aggregate (Sims) Kosterm is a traditional Chinese herb used for thousands of years in the treatment of gastrointestinal diseases. Previously, we have demonstrated that the extracts of Lindera aggregate have good anti-UC effects, but their pharmacodynamic active components have not been fully clarified. Therefore, we explored the therapeutic effect of Linderanine C (LDC), a characteristic component of Lindera aggregata, on UC and its mechanism in this study. Firstly, we found that LDC could significantly reduce the disease activity index of UC and improve shortened colon and pathological changes in vivo. Colon tissue transcriptomics suggested that the anti-UC effect of LDC might be related to its anti-inflammatory activity. Cellular experiments revealed that LDC could inhibit the expression of the M1 cell marker CD86 in RAW264.7 cells, reduce the production of inflammatory mediators such as IL-6 and TNF-α, and have good anti-inflammatory activity in vitro. Cellular transcriptomics reveal the potential involvement of the MAPK signaling pathway in the anti-inflammatory effect of LDC. The co-culture assay confirmed that LDC could significantly reduce inflammation-mediated intestinal epithelial cell injury. In conclusion, LDC was able to inhibit macrophage M1 polarization and reduce inflammatory mediator production by inhibiting the MAPK signaling pathway, effectively improving UC.

中文翻译：

---

乌药碱 C 通过抑制 MAPK 信号通路调节巨噬细胞极化对抗溃疡性结肠炎


溃疡性结肠炎（UC）是一种累及直肠和结肠粘膜及粘膜下层的慢性非特异性炎症性疾病。乌药聚合 (Sims) Kosterm 是一种传统中草药，在治疗胃肠道疾病方面已有数千年的历史。此前我们已证明乌药聚集体提取物具有良好的抗UC作用，但其药效活性成分尚未完全阐明。因此，本研究探讨乌药的特征成分乌药碱C（LDC）对UC的治疗作用及其机制。首先，我们发现LDC可以显着降低UC的疾病活动指数，改善结肠缩短和体内病理变化。结肠组织转录组学表明LDC的抗UC作用可能与其抗炎活性有关。细胞实验表明，LDC能够抑制RAW264.7细胞中M1细胞标志物CD86的表达，减少IL-6、TNF-α等炎症介质的产生，具有良好的体外抗炎活性。细胞转录组学揭示了 MAPK 信号通路在 LDC 抗炎作用中的潜在参与。共培养测定证实LDC可以显着减轻炎症介导的肠上皮细胞损伤。综上所述，LDC能够通过抑制MAPK信号通路，抑制巨噬细胞M1极化，减少炎症介质产生，有效改善UC。