Pharmacometabolomics and mass spectrometry imaging approach to reveal the neurochemical mechanisms of Polygala tenuifolia

作者：Qian Li, Jin-Peng Bai, Yuxue Ma, Yu Sun, Wenbin Zhou, Zhaoying Wang, Zhi Zhou, Zhonghua Wang, Yanhua Chen, Zeper Abliz · 发表于：Journal of Pharmaceutical Analysis · 年份：2024 · DOI：10.1016/j.jpha.2024.100973 · 被引用次数：10 · 研究领域：Natural Compound Pharmacology Studies、Ziziphus Jujuba Studies and Applications、Allelopathy and phytotoxic interactions

Polygala tenuifolia, commonly known as Yuanzhi (YZ) in Chinese, has been shown to possess anti-insomnia properties. However, the material basis and the mechanism underlying its sedative-hypnotic effects remain unclear. Herein, we investigated the active components and neurochemical mechanism of YZ extracts using liquid chromatography tandem mass spectrometry (LC-MS/MS)-based pharmacometabolomics and Mass Spectrometry Imaging (MSI)-based spatial resolved metabolomics. According to the results, seventeen prototypes out of 101 ingredients in the YZ extract were detected in both the plasma and brain, which might be the major components contributing to the sedative-hypnotic effects. Network pharmacology analysis revealed that these prototypes may exert their effects through neuroactive ligand-receptor interaction, serotonergic synapse, and dopaminergic synapse, and dopaminergic synapse, among other pathways. LC-MS/MS-based targeted metabolomics and Western blot (WB) revealed that tryptophan-serotonin-melatonin (Trp-5-HT-Mel) and tyrosine-norepinephrine-adrenaline (Tyr-Ne-Ad) are the key regulated pathways. Dopa decarboxylase (DDC) upregulation and phenylethanolamine N-methyltransferase (PNMT) downregulation further confirmed these pathways. Furthermore, MSI-based spatially resolved metabolomics revealed notable alterations in serotonin (5-HT) in the pineal gland, and Ad in the brainstem, including the middle brain, pons, and hypothalamus. In summary, this study illustrates the eff...