中药是由多种化学成分构成的复杂体系,其发挥疾病治疗作用的最大特色就在于其所含的多种活性成分通过多靶点协同作用得以实现。以往针对中药的药理机制研究大多关注于对单一信号通路的检测或是对整体蛋白质组学变化的表型分析,尚无有效方法针对中药的直接作用靶点开展研究。因此无法从靶点源头上解析中药的分子作用机制,难以科学诠释其传统功效,进而严重影响其临床应用和国际化推广。该文主要针对中药复杂体系的直接作用靶点(群)的鉴定进行初步的方法学探讨,提出了基于光敏偶联技术的中药化学成分固相亲合载体的制备及靶点蛋白富集和鉴定策略,并在此基础上探讨了该策略的优势和局限性,同时针对今后的发展方向和有待解决的问题提出了新的见解。希望对于从事中药药理学研究特别是中药靶点确证的相关人员具有一定的指导和借鉴意义。
Traditional Chinese medicine( TCM) is a complex system with multiple chemical compositions. The most significant character of TCM is that the chemical compositions interact with each other by multi-target synergism to treat diseases. Previous reports mainly focused on the investigation of single signaling pathway detection or the phenotypic analysis of proteomics difference; however,no studies have been conducted on the identification of direct targets of TCM. Therefore,it is difficult to analyze the molecular mechanism of traditional Chinese medicine from the target source,and it is difficult to explain its traditional efficacy scientifically,thus seriously affecting its clinical application and internationalization. In this article,we discussed the methodology for the identification of direct TCM targets( groups),and presented the strategy for preparation of TCM chemical composition solid coupling beads,as well as of enrichment and identification strategy of target proteins based on photosensitive coupling technique. We also discussed the advantages and limitations of this strategy,and put forward some new ideas for the future developments. We hope this article can provide some guidance and reference significance for the researchers on TCM pharmacology study,especially on target identification.