加味五子衍宗丸神经保护作用靶点群的鉴定与功能分析

Identification and function analysis of neuroprotective targets group of modified Wuzi Yanzong pill

中药复杂体系的作用靶点群鉴定是中药药理机制研究的关键。该研究构建了一种表面键合有光敏二苯甲酮基团的磁性微球,利用紫外光激发下二苯甲酮基团活化并与中药化学成分中的碳氢键发生共价键合的特性,将中药加味五子衍宗丸的化学成分组键合到磁性微球表面,并与神经细胞裂解液共孵育,进而富集加味五子衍宗丸对应的神经保护靶点群。针对靶点群进行蛋白质组学分析,共发现32个潜在结合靶点。KEGG分析发现这些靶点主要与Hippo和Cell cycle信号通路关系密切,提示加味五子衍宗丸可能参与调控神经干细胞增殖和促进神经细胞分化。该研究从靶点源头上解释了加味五子衍宗丸发挥抗痴呆和神经保护作用的潜在药理机制,进而也提供了一种用于解析中药复杂成分体系作用靶点群的研究方法,可为今后中药方剂药理机制的科学诠释提供重要的方法学借鉴与参考。

Targets group identification in complex Chinese medicine system is a key step for revealing the potential mechanism of Chinese medicine. The solid beads with magnetic core and benzophenone-modified surface were made in our study,and then benzophenone was activated and cross-linked with the C-H bonds of chemical compositions in Chinese medicines under UV excitation. Thus the chemical compositions of modified Wuzi Yanzong pill（ MWP） were linked to the solid bead surface,and enriched the neuroprotective targets group of MWP after being co-incubated with nerve cell lysate. We performed proteomics analysis on these targets and discovereda total of 32 potential binding targets. KEGG analysis revealed that these targets were mainly associated with Hippo and Cell cycle signaling pathways,suggesting that MWP might be involved in regulating the proliferation and differentiation of neural stem cells. Our findings elucidate the potential targets and mechanism of MWP on anti-dementia and neuroprotection,and further providean approach for investigating the targets group in complex Chinese medicine system. This novel method may provide methodological references for exploring the pharmacological mechanism of Chinese medicinal formulae in the future.