Zhejiang TCM Key Laboratory of Pharmacology and Translational Research of Natural Products, School of Pharmaceutical Sciences, Hangzhou Medical College, Hangzhou, Zhejiang 311399, China.
Department of Colorectal Surgery, Zhejiang Provincial People's Hospital, Affiliated People's Hospital of Hangzhou Medical College, Hangzhou, Zhejiang 310014, China.
Biomed Pharmacother. 2024 Sep;178:117239. doi: 10.1016/j.biopha.2024.117239. Epub 2024 Aug 3.
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.
溃疡性结肠炎（UC）是一种累及直肠和结肠黏膜及黏膜下层的慢性非特异性炎症性疾病。山胡椒（Sims）Kosterm 是一种传统的中药，用于治疗胃肠道疾病已有数千年的历史。先前，我们已经证明，山胡椒提取物具有良好的抗 UC 作用，但它们的药效活性成分尚未得到充分阐明。因此，我们在本研究中探讨了山胡椒特征成分山胡椒胺 C（LDC）对 UC 的治疗作用及其机制。首先，我们发现 LDC 可显著降低 UC 的疾病活动指数，改善缩短的结肠和体内的病理变化。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 可抑制 RAW264.7 细胞中 M1 细胞标志物 CD86 的表达，减少 IL-6 和 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 信号通路可能参与了 LDC 的抗炎作用。共培养试验证实，LDC 可通过抑制 MAPK 信号通路显著减轻炎症介导的肠上皮细胞损伤。总之，LDC 可抑制巨噬细胞 M1 极化并减少炎症介质的产生，从而有效改善 UC。
