Study On The Potential Effective Constituent Of Semen Ziziphi Spinosae

Rationales: Semen Ziziphi Spinosae(SZS)from medicinal plants,is commonly used in traditional Chinese medicine in treating insomnia.With the traditional pattern of activity screening "Extraction and Separation,Component identification,active ingredents filter",has clarified some active ingredients of SZS for the treatment of insomnia,for it's effectiveness,safety and quality control,to provide a scientific basis.But the research mode is not on the whole interpretation of the global effective components of SZS,the mode divided the integrity of drugs and ignore the interaction between the ingredients.Therefore,from in vivo and in vitro,a comprehensive understanding of potential effective components of SZS in the body,combined with the network pharmacology to perspective of the potential active components from ?compnents-effect? way.Objective: In this paper,the preferred choice of clinical treatment of insomnia of Ziziphi Spinosae Semen as the research object,from the chemical compositioncomponents in body-the potential effective compositions way,to explore the potential active components of SZS the treatment of insomnia.Methods: Intervention by 1H-NMR metabonomics study of SZS PCPA-induced insomnia and the potential biomarkers in serum of rats,and to evaluate its effectiveness.The establishment of RSLC Q-Extractive orbit high resolution ion trap mass spectrometry analysis technology and identification of the chemical constituents of water extract of SZS.The use of the established analysis method in rat serum after administration of the aqueous extract of SZS in the study of metabolites,to find in vivo-in vitro group of substances.Finally use the Network Pharmacology method to build into the blood componentsinsomnia protein network to select potential effective and active constituents of SZS.Results: 1.By 1H-NMR metabonomics study of insomnia rats serum and to find 16 biomarkers of insomnia.Consisting of 8 amino acids(glycine,tryptophan,methionine,alanine,phenylalanine,glutamic acid,etc),Carnitine,glutamine,succinic acid,creatine,choline,betaine,glycerol and glucose.The results showed that diazepam group on the role of 7 biomarkers of insomnia has a callback,the low-dose group has the callback function for 5 biomarkers,middle-dose and high-dose group on the 13 biomarkers has a callback function.2.Identified and inferred 25 compounds of water extract of SZS,including 12 flavonoids,8 triterpenoids saponins,2 fatty acids and 3 alakoids.After the rat oral aqueous extract of SZS,in vivo-in vitro correlation analysis of substance,in the serum of 15 kinds of chemical constituents were identified,including 6 flavonoids and 1 metabolites,5 triterpenoid saponins and 2 alkaloids and 1 metabolite.3.Cytoscape software construction of insomnia protein protein interaction networks and into the blood components-insomnia protein network,find insomnia disease related targets for 143,the main is that GABA receptors,5-HT receptors,adrenergic receptors,dopamine receptors and glutamate receptors.Preliminary selection of 5 potential effective compositions of SZS,such as: spinosin,jujuboside a,zizyphusine,apigenin and coclaurine.Conclusion: In this paper,using the theory and technology of pharmacology,information science and analytical chemistry,to realize ?the combination of in vivo and in vitro? and ?combination of the material and the effect? mode of research,to explore the potential effective compositions of SZS in treatment of insomnia.Firstly from the perspective of metabolomics to study the effectiveness of the aqueous extract of SZS treatment of insomnia,then defined the category of the chemical constituents of SZS,and the chemical components of in vivo-in vitro correlation,identified the types and quantities of ingredients into the blood,finally build into the blood components-insomnia protein network,select 5 potential effective substances of SZS.This study defined 5 potential active constituents of SZS to treat insomnia,provide scientific basis for the medicinal resources and the quality evaluation of traditional Chinese medicine which Contains Semen Ziziphi Spinosae.