中文摘要
溃疡性结肠炎(UC)是一种多因素诱导的非特异性炎症疾病,被WHO列为现代难治病之一。中药方剂治疗该类复杂疾病具有突出的优势。研究表明,抗宫炎方水提取物(KGY-wE)具有显著的治疗UC的作用,但其药效物质基础和作用机制尚不明确。课题组前期研究提示KGY-wE可能通过调节琥珀酸-HIF-1α信号通路和肠道微生态平衡来治疗UC。本项目拟开展工作如下:①结合膜分离技术和细胞活性筛选KGY-wE有效成分群,对其进行制备工艺的优化和质量控制;②基于DSS诱导的UC小鼠模型评价KGY-wE有效成分群的整体药效,结合宏基因组与代谢组分析,发现UC相关菌群及功能性代谢物,并进行体外验证;③基于以上线索,在细胞、动物水平探讨KGY-wE有效成分群对UC中琥珀酸产生的调节机制。最终,在“方剂组学”思路的指导下,以KGY-wE质量控制为前提,结合药理学、“组学”和生物信息学等手段,深入阐明其治疗UC的科学内涵。
英文摘要
Ulcerative colitis (UC), as a multiple factors induced chronic nonspecific inflammatory disease, was classified as one of the modern refractory disease by WHO. Chinese medicinal formula, has showed distinct advantages in the management of such complex diseases. The previous studies suggested that the aqueous extract of kanggongyan formula (KGY-wE) had beneficial action in the regulation of UC. However, up to now, little is known about its potential basis and mechanism of action. Based on our previous studies, the project proposed that KGY-wE improved UC by regulation of succinate-HIF-1α signaling pathway and gut microbiota balance. This project will focus on: ①To screen, preparation, and quality control of active ingredients by combining membrane separation and bioactive screening technologies; ②to evaluate the therapeutic effects of KGY-wE by DSS-induced UC mice model, and find out flora and functional metabolites related to UC by combining with metagenomics and metabolomics, then to validate in vitro; ③to test this hypothesis, we investigated the effects of KGY-wE on UC by focusing on its regulation of succinate-HIF-1α signaling pathway in the cell and animal level. Eventually, under the guidance of Fangjiomics, and the premise of quality control of KGY-wE, the action material basis and mechanism of Kanggongyan formula will be explored by using pharmacology, “omics”, bioinformatics and other multi-disciplinary technologies. We expect that this study will contribute to new ideas and methods for modernization of Chinese medicine formula.
