Mechanism of Sour Jujube Kernel-five-flavour Berry in the Treatment of Insomnia based on Network Pharmacology and Molecular Docking

Background: The incidence of insomnia is increasing annually worldwide. Most Western tranquilisers have side effects, such as strong dependence and notable withdrawal reactions. The sour jujube kernel and five-flavour berry can calm the mind and improve sleep, but the underlying mechanism is still unclear. Objective: We investigated the active ingredients and mechanism of action of the sour jujube kernel-fiveflavour berry pair in treating insomnia. Methods: The chemical compositions and targets of sour jujube kernels and five-flavoured berries were obtained from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform, Pub- Chem, and PharmMapper. Insomnia disease targets were screened using the GeneCards, Online Mendelian Inheritance in Man, and Therapeutic Target Database. We constructed shared target data for topological analysis and network construction using the STRING database and the Cytoscape software. Gene Ontology functional and metabolic pathway analyses were performed using the DAVID database and validated through molecular docking using AutoDock and PyMOL software. Results: This study demonstrated that the sour jujube kernel and five-flavour berry combination primarily addresses insomnia through the activity of eight hub genes: ALB, CASP3, DRD1, ESR1, MAOB, NOS3, SLC6A3, and SLC6A4. Molecular docking simulations showed that jujuboside A exhibited robust docking to these hub genes, whereas longikaurin A showed a strong binding affinity with ALB and ESR1. Conclusion: We establish a theoretical foundation for further experimental studies, which may lead to the application of sour jujube kernel in clinical practice.