中药活性成分直接作用靶点鉴定研究方法及应用

中药因其确切的临床疗效受到越来越多的关注。随着对中药活性成分的深入研究,现已发现很多具有独特活性和药效的潜在创新药物。然而,如何进一步对其药效机制进行挖掘、发现全新的机制和靶点,成为创新中药研究的关键。中药活性成分靶点鉴定一直是研究者们所探寻的重要课题。随着化学生物学技术尤其是化学蛋白组学技术的发展,越来越多的方法被建立并用于中药活性成分的靶点鉴定。简单来说,这些方法大致可被分为标记法和非标记法。标记法是通过将中药活性成分改造为活性探针,进而探寻它们的作用靶标蛋白;而非标记法主要是基于中药活性成分和靶标蛋白结合后会影响靶标蛋白的热稳定性等生物物理性质从而识别可能的作用靶点。主要针对这2大类靶点鉴定方法进行归纳整理,从方法原理、大致操作流程、应用、优缺点等方面进行阐述,为中药活性成分靶点鉴定提供一定的参考,以期助力中药创新研究。

Research method and application for identifying direct target of bioactive components from traditional Chinese medicine

Chinese herbal medicine has been paid more and more attention because of its exact clinical efficacy. With the in-depth study of the bioactive components of Chinese herbal medicine, many potential innovative drugs with unique activity and efficacy have been discovered. However, how to further explore the pharmacodynamic mechanism and discover new mechanisms and targets has become the key to the original innovative research of Chinese herbal medicine. The target identification of bioactive components in Chinese herbal medicine has always been an important topic that researchers have been exploring. With the development of chemical biology technology, especially chemical proteomics technology, more and more methods have been established for the identification of bioactive components in Chinese herbal medicine. These methods mainly include labeling and non-labeling methods. The labeling method is to transform the bioactive components into active probes, and then explores their target proteins, while the non-labeling method is mainly based on the biophysical properties such as the thermal stability of target proteins which will be affected by the combination of bioactive components of Chinese herbal medicine and target proteins, so as to identify possible targets. In this paper, these two kinds of target identification methods are summarized and elaborated from the aspects of principle, general operation process, application, advantages and disadvantages, etc., which provide a certain reference for the target identification of bioactive components, and expect to help the original innovative research of Chinese herbal medicine.