手机版 客户端

基于琥珀酸-HIF-1α信号通路和肠道微生态平衡探讨抗宫炎方治疗溃疡性结肠炎的药效物质基础和作用机制

基于琥珀酸-HIF-1α信号通路和肠道微生态平衡探讨抗宫炎方治疗溃疡性结肠炎的药效物质基础和作用机制
  • 导航:首页 > 科学基金
  • 批准号:81673568
  • 批准年度: 2016年
  • 学科分类:中药药效物质(H2803) |
  • 项目负责人:刘丽芳
  • 负责人职称:教授
  • 依托单位:中国药科大学
  • 资助金额:57万元
  • 项目类别:面上项目
  • 研究期限:2017年01月01日 至 2020年12月31日
  • 中文关键词: 琥珀酸;HIF-1α;微生态平衡;宫炎方;溃疡性结肠炎
  • 英文关键词:Kanggongyan formula;ulcerative colitis;action materials;succinate-HIF-1α signaling pathway;gut micro

项目摘要

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.

评估说明

    国家自然科学基金项目“基于琥珀酸-HIF-1α信号通路和肠道微生态平衡探讨抗宫炎方治疗溃疡性结肠炎的药效物质基础和作用机制”发布于爱科学iikx,并永久归类于相关科学基金导航中,仅供广大科研工作者查询、学习、选题参考。国科金是根据国家发展科学技术的方针、政策和规划,以及科学技术发展方向,面向全国资助基础研究和应用研究,发挥着促进我国基础研究源头创新的作用。国科金的真正价值在于它能否为科学进步和社会发展带来积极的影响。

此文由 爱科学 编辑!:首页 > 科学基金 > 科学基金3 » 基于琥珀酸-HIF-1α信号通路和肠道微生态平衡探讨抗宫炎方治疗溃疡性结肠炎的药效物质基础和作用机制

推荐文章