基于尤斯灌流系统的诃子特征化学成分抗溃疡性结肠炎活性及机制研究

溃疡性结肠炎的发生率近年来呈不断上升的趋势，目前临床使用的西药会导致诸多不良反应。民族药物是发现新药的重要源泉，诃子有“藏药之王”的称号，具有涩肠止泻的传统功效。前期研究表明诃子次酸及诃子鞣花单宁类化合物是诃子的特征化学成分，具有潜在的抗炎活性。然而，这类化合成分因含量低、结构相似而难于分离提取，故未见基于实验动物的抗炎药理学研究，从而限制了对诃子所含活性物质的深度发掘与利用。本项目基于尤斯灌流系统对诃子特征化合物诃子次酸的半体内抗炎活性、跨结肠膜转运代谢以及体外抗炎活性进行研究，从炎症信号通路调控及肠道代谢的角度探究诃子次酸抗溃疡性结肠炎的分子机制，进而阐明诃子在溃疡性结肠炎治疗中的作用机理和揭示其“涩肠止泻”的现代科学内涵，为诃子的临床用药和合理开发提供科学依据，也为民族医药来源的微量特征化合物体内药理活性筛选及作用机制研究提供新思路与新方法。

The incidence of ulcerative colitis (UC) has been increasing in recent years, and western medicine currently used in clinical practice may cause many adverse reactions. Ethnic medicine is an important source of discovering new drugs. Terminalia chebula is "the king of Tibetan medicine" with the traditional effect on astringent intestines to stop diarrhea. Previous studies showed that chebulic acid (CA) and chebulic ellagitannins are the characteristic chemical components of Terminalia chebula, which have potential anti-inflammatory activities. However, due to less abundance and similar structure of these compounds, it is difficult to obtain monomers to study their pharmacological activities in vivo, which limits the further research and application of the active substances contained in Terminalia chebula. This proposal aims to use the characteristic compound of Terminalia chebula, CA, to do ex vivo anti-inflammatory research and metabolic research of trans-colon epithelium base on Ussing chamber system, as well as in vitro anti-inflammatory research through cell model to clarify the molecular mechanisms of CA against UC from the perspective of inflammatory signaling pathway regulation and trans-intestinal metabolism. It will further explain the mechanism of Terminalia chebula in UC treatment and the modern scientific connotation that Terminalia chebula has the effect on stopping diarrhea, which provides scientific and theoretical basis for the clinical use and reasonable development of Terminalia chebula. Simultaneously, Ussing chamber system is used for pharmacological research provides new idea and technique for activity screening and mechanism study of less abundant characteristic compounds from ethnic medicine.