基于疾病网络发现消渴安方抗糖尿病多向药理学效应物质群研究

Traditional Chinese medicine usually exhibits polypharmacological effects during treating complex diseases. The key point of active constituent identification is to characterize the constituent group with polypharmacological effects (CGP) whose therapeutic activity is substantially equivalent to that of the whole formula. This application aims at demonstrating the antidiabetic constituent group with polypharmacological effects from Xiaokean formula. A novel idea about Integrated Multiactivity Index (IMI) is proposed, which simultaneously values the content and the multiple anti-diabetic activity of the constituents, and the importance of each aspect of diabetes. Qualitative and quantitative analysis will be carried out with HPLC-MS to figure out the contents of constituents. Text-mining and bioassays will performed to evaluate the multiple anti-diabetic activity of the constituents. The constructed type 2 diabetes network will be analyzed to assess the importance of each aspect of diabetes. Then, the IMI would be established to find out the potential CGP which will evaluated by in vivo assays. Finally, the CGP of Xiaokean formula would be characterized. This study might offered a paradigm for the active constituents identification from traditional Chinese medicine for complex diseases.

中药常通过多向药理学作用对复杂性疾病起到整合调节作用。中药药效物质发现的关键在于找出一组与全方药效相当，且协同起效的多向药理学效应物质群。本申请拟围绕该科学问题，以临床确有疗效的消渴安方为研究载体，综合运用中药化学、网络药理学、细胞分子生物学等研究手段，采用液质联用技术对消渴安方成分进行定性、定量分析，通过文献挖掘及实验研究全面获取消渴安方中各成分抗糖尿病多向药理学效应信息，通过对已构建的2型糖尿病疾病网络子簇/模块分析，表征糖脂代谢、氧化应激、炎症等机制环节对疾病发生发展的重要度，据此构建"多向整合药效指数"用以评价各成分对全方抗糖尿病药效贡献度，并以此筛选出多向药理学候选效应物质群，通过动物实验验证该候选物质群与全方药效相当，阐明消渴安方抗2型糖尿病的药效物质基础。这一研究有望建立一种面向复杂性疾病的中药药效物质发现的新模式，为消渴安方二次开发及新型中药创制提供依据，促进中药现代化。

治疗复杂性疾病的中药，常通过多向药理学作用对复杂性疾病进行整合调节。如能找到一组与中药全方药效相当的效应成分群，则可用于中药的质量控制，促进中药二次开发。本项目以临床治疗糖尿病的消渴安方为研究载体，综合运用中药化学、网络药理学等研究方法，采用液质联用技术对消渴安方化学成分进行定性、定量分析，通过文献挖掘等方法获取消渴安方中成分抗糖尿病的多向药理学效应信息，通过对2型糖尿病疾病相关生物分子网络进行网络药理学分析，构建“多向整合药效指数”（Integrated Multiactivity Index, IMI）用以评价各成分对消渴安全方抗糖尿病药效贡献度，据此筛选出候选效应成分群，并通过动物实验进行验证。本项目初步揭示了消渴安方的多向药理学效应成分群，可进一步推广使用到其他中药的研究中，促进中药现代化发展。