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

作　　者：Qian Li Jinpeng Bai Yuxue Ma Yu Sun Wenbin Zhou Zhaoying Wang Zhi Zhou Zhonghua Wang Yanhua Chen Zeper Abliz 

机构地区：[1]Key Laboratory of Mass Spectrometry Imaging and Metabolomics(National Ethnic Affairs Commission),Minzu University of China,Beijing,100081,China [2]Key Laboratory of Ethnomedicine of Ministry of Education,School of Pharmacy,Minzu University of China,Beijing,100081,China [3]Center for Imaging and Systems Biology,College of Life and Environmental Sciences,Minzu University of China,Beijing,100081,China [4]State Key Laboratory of Bioactive Substance and Function of Natural Medicines,Institute of Materia Medica,Chinese Academy of Medical Sciences,Peking Union Medical College,Beijing,100050,China

出　　处：《Journal of Pharmaceutical Analysis》2024年第7期1035-1046,共12页药物分析学报（英文版）

基　　金：support from the National Key R&D Program of China(Grant No:2022YFC3401003);the National Natural Science Foundation of China(Grant No:21927808);the National Natural Science Foundation of China(Grant No:22104160);the National Key Research and Development Program of China(Grant No:2017YFC1704006);the Innovation Team of Ethnomedicine of National Ethnic Affairs Commission,China.We thank all the research staff who contributed to the study.

摘　　要：Polygala tenuifolia,commonly known as Yuanzhi(YZ)in Chinese,has been shown to possess antiinsomnia 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,17 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,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 Nmethyltransferase(PNMT)downregulation further confirmed these pathways.Furthermore,MSI-based spatially resolved metabolomics revealed notable alterations in 5-HT in the pineal gland(PG),and Ad in the brainstem,including the middle brain(MB),pons(PN),and hypothalamus(HY).In summary,this study illustrates the efficacy of an integrated multidimensional metabolomics approach in unraveling the sedative-hypnotic effects and neurochemical mechanisms of a Chinese herbal medicine,YZ.

关 键 词：Polygala tenuifolia Pharmaceutical metabolomics Spatially resolved metabolome Sedative-hypnotic Neurochemical mechanisms 

分 类 号：R969.1[医药卫生—药理学]