NATURAL PRODUCT RESEARCH AND DEVELOPMENT ›› 2021, Vol. 33 ›› Issue (1): 114-126.doi: 10.16333/j.1001-6880.2021.1.015

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Study on the mechanism of Zhufuling in insomnia based on network pharmacology,molecular docking and experimental verification

ZHOU Yang1,GUO Leng-qiu1,LIU Xun1,TAN Ru-lan1,ZHONG Qi-xin3,ZENG Feng2*   

  1. 1 Suzhou Key Laboratory of Medical Biotechnology,Suzhou Vocational Health College,Suzhou 215009,China;2Artemisinin Research Center,Guangzhou University of Chinese Medicine,Guangzhou 510445,China;3Shenzhen Hospital,Guangzhou University of Chinese Medicine,Shenzhen 518034,China

  • Online:2021-01-28 Published:2021-01-28

Abstract:

In order to explore the possible mechanism of Zhufuling in the treatment of insomnia,the active components and potential targets of Zhufuling were screened by TCMSP platform,BAT-MAN database,TCMID database,STITCH database and literature mining;related targets of insomnia diseases were obtained by TTD database,OMIM database,GeneCards database and CTD database,and the active component target network and target protein interaction network were constructed by using Cytoscape software and String database,and the target organs were located by BioGPS database,and GO function and KEGG pathway enrichment analysis were carried out based on David database,and Autodock_Vina software was used to verify the molecular docking of active components and core targets.Western blot was used to verify the effect of Zhufuling on GABA receptor α1 subunit gene (GABRA1) and GABA receptor γ2 subunit gene (GABRG2).Finally,33 kinds of active components,267 kinds of potential targets and 36 kinds of intersecting targets with insomnia were screened,which were mostly used in brain,heart and other organs.The results of molecular docking showed that GABRA1 and GABRG2 could spontaneously combine with the active components and form stable conformations by hydrogen bonding and other intermolecular forces.189 GO entries and 24 KEGG pathways were obtained by enrichment analysis,which mainly involved GABA signaling pathway and 5-hydroxytryptamine (5-HT) signaling pathway.Western blot showed that Zhufuling could enhance the expression of GABRA1 and GABRG2 protein in mouse brain.Through network pharmacology,molecular docking and Western blot experiments,we found that Zhufuling may play a calming and tranquilizing effect through multi-component,multi-target and multi-channel synergistic effect,which provides new ideas and methods for further research on the mechanism of Zhufuling in the treatment of insomnia.

Key words: Zhufuling, insomnia, network pharmacology, molecular docking, GABA receptor

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