NATURAL PRODUCT RESEARCH AND DEVELOPMENT ›› 2025, Vol. 37 ›› Issue (8): 1552-1562. doi: 10.16333/j.1001-6880.2025.8.017 cstr: 32307.14.1001-6880.2025.8.017

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Mechanism of Ziziphi Spinosae Semen oil in improving insomnia based on network pharmacology and experimental verification

PAN Mei-lu1,2,LIU Ying-jie2,HU Fei-zi2,WANG Shao-qing2,SUN Hui-zhu2,LIU Xue-li2*   

  1. 1College of Chemical and Pharmaceutical Engineering, Hebei University of Science and Technology, Shijiazhuang 050018, China; 2Hebei Institute for Drug and Medical Device Control, Shijiazhuang 050227,China
  • Online:2025-08-25 Published:2025-08-25

Abstract:

This study aims to investigate the mechanism of Ziziphi Spinosae Semen oil (ZSSO) in improving insomnia by using network pharmacology and experimental verification. Firstly, the gas chromatography-mass spectrometry (GC-MS) instrument was used to collect data, and the chemical components of ZSSO were identified from the existing literature and relevant databases. Next, the SwissTargetPrediction database was used to retrieve the targets of the ZSSO components. Meanwhile, the targets of insomnia were identified from the GeneCards, OMIM, and DisGeNET databases. Then the associations among potential active ingredients, key targets, and signaling pathways of ZSSO components were analyzed by the Venny, Cytoscape 3.10.0, String, and DAVID databases. And finally, the experimental results were validated by using a rat model of insomnia. The results of GC-MS analysis showed that twenty-seven chemical components were identified in ZSSO. The results of network pharmacology showed that the active ingredients of ZSSO in improving insomnia may be oleic acid, linoleic acid and other four ingredients, and the key targets may be androgen receptor (AR), peroxisome proliferator activated receptor gamma (PPARG), gamma-aminobutyric acid type A receptor subunit beta2 (GABRB2), and gamma-aminobutyric acid type B receptor subunit1 (GABBR1), which mainly enriched in neuroactive ligand-receptor interaction, cyclic adenosine monophosphate (cAMP) and other signaling pathways. The in vivo experimental results showed that the ZSSO could significantly increased the content of 5-hydroxytryptamine in serum and brain tissue, and enhanced the protein expression of AR and PPARG in the brain. The study suggested that the ZSSO can effectively improve insomnia, and the mechanism of action may be related to the enhancement of AR and PPARG in the brain.

Key words: Ziziphi Spinosae Semen oil, insomnia, network pharmacology, molecular docking, active ingredients

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