Integration of High-Resolution LC-Q-TOF Mass Spectrometry and Multidimensional Chemical−Biological Analysis to Detect Nanomolar-Level Acetylcholinesterase Inhibitors from Different Parts of Zanthoxylum nitidum

作者：Jia‐Nuo Zhang, Zhidong Pei, Wenyu Wang, Ming‐Yue Zhao, Wenhan Pei, Hui Zhang, Haibo Yin, Tian‐Min Wang, Gui-Zhong Xin, Ming Xie, Tingguo Kang, Yuehua Chen, Hui‐Peng Song · 发表于：Journal of Agricultural and Food Chemistry · 年份：2024 · DOI：10.1021/acs.jafc.4c00866 · 被引用次数：9 · 研究领域：Cholinesterase and Neurodegenerative Diseases、Chemical synthesis and alkaloids、Plant chemical constituents analysis

Zanthoxyli radix is a popular tea among the elderly, and it is believed to have a positive effect on Alzheimer’s disease. In this study, a highly effective three-step strategy was proposed for comprehensive analysis of the active components and biological functions of Zanthoxylum nitidum (ZN), including high-resolution LC-Q-TOF mass spectrometry (HRMS), multivariate statistical analysis for heterogeneity (MSAH), and experimental and virtual screening for bioactivity analysis (EVBA). A total of 117 compounds were identified from the root, stem, and leaf of ZN through HRMS. Bioactivity assays showed that the order of acetylcholinesterase (AChE) inhibitory activity from strong to weak was root > stem > leaf. Nitidine, chelerythrine, and sanguinarine were found to be the main differential components of root, stem, and leaf by OPLS-DA. The IC 50 values of the three compounds are 0.81 ± 0.02, 0.14 ± 0.01, and 0.48 ± 0.01 μM respectively, indicating that they are potent and high-quality AChE inhibitors. Molecular docking showed that pi-pi T-shaped interactions and pi-lone pairs played important roles in AChE inhibition. This study not only explains the biological function of Zanthoxyli radix in alleviating Alzheimer’s disease to some extent, but also lays the foundation for the development of stem and leaf of ZN.