矮地茶抗溃疡性结肠炎药效物质基础表征及整合作用机制研究

溃疡性结肠炎病情迁延难愈，易反复发作，严重威胁人类健康，被世界卫生组织列为现代难治病之一。矮地茶具有显著的抗炎及免疫调节作用，可作为治疗溃疡性结肠炎的潜在中药，但其抗溃疡性结肠炎的药效物质基础及整合作用机制尚无报道。本项目拟以中医药整体观理论为指导，融合多学科技术手段，表征矮地茶抗溃疡性结肠炎主效成分（群），探讨矮地茶抗溃疡性结肠炎整合作用机制。在系统表征矮地茶化学物质组的基础上，基于葡聚糖硫酸钠诱导溃疡性结肠炎等体内外模型确证矮地茶抗溃疡性结肠炎药效，结合“活性成分群缺失/捕获”和“定量指纹图谱/药效关系”技术，快速发现矮地茶抗溃疡性结肠炎主效成分（群）；应用代谢组学、肠道微生态学及分子生物学技术，揭示矮地茶可能通过调控肠道菌群引起代谢物改变，激活芳香烃受体，调控PI3K/AKT/mTOR信号通路，发挥抗溃疡性结肠炎作用的整合机制。该项目以期为矮地茶临床合理用药及新药创制提供科学依据。

Ulcerative colitis is difficult to recover，and easy to be attacked repeatedly. It is listed as one of the modern refractory diseases by the World Health Organization and poses a serious threat to human health. Japanese Ardisia Herb is a potential Chinese medicine for the treatment of ulcerative colitis according to its potent anti-inflammatory and immunomodulatory effects. However, the effective components and integrated mechanism for the treatment of ulcerative colitis remain unclear. Guided by the holistic concept of Traditional Chinese Medicine, integrating multidisciplinary technical, this project focuses on discovering the effective component combination in Japanese Ardisia Herb for the treatment of ulcerative colitis and exploring its integrated mechanism. After the systematic characterization of its chemical constituents, the efficacy of Japanese Ardisia Herb against Ulcerative colitis is confirmed by the in vitro and in vivo models such as dextran sulfate sodium-induced ulcerative colitis. The “active components fishing and knockout” and “quantitative spectrum-effect relationships” technique, combined with the pharmacological models, is applied to discover and confirm the effective components combination in Japanese Ardisia Herb for the treatment of ulcerative colitis. Furthermore, the integrated mechanism for treatment of ulcerative colitis is investigated based on metabolomics, intestinal microecology, and molecular biology approach, as the effective component combination may activate the aryl hydrocarbon receptors and regulate the PI3K/AKT/mTOR signaling pathway by the metabolite changes caused by gut microbiota. This project would be helpful for the clinical application and new drug creation of Japanese Ardisia Herb.