The
acupoint application of Euodiae Fructus at Yongquan(KI1) can significantly improve the sleep quality of patients with
insomnia with
berberine as the main effective component for the efficacy. Nineteen active compounds and 203
drug targets were screened out from
Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP). After comparison with GeneCards and Online Mendelian Inheritance in Man(OMIM), 24 common genes of diseases and drugs were obtained. STRING 11.0 was used to construct a
protein-
protein interaction(PPI) network of the overlapping genes, and Matthews correlation coefficient(MCC) was employed to screen the core genes, which were then subjected to enrichment analysis with gene ontology(GO) and Kyoto encyclopedia of genes and genomes(KEGG). The results revealed that the main compounds of Euodiae Fructus, such as
berberine and
rutaecarpine, participated in the biological processes(such as
neurotransmitter receptor activity) by regulating
C-reactive protein(CRP),
estrogen receptor 1(ESR1), 5-hydroxytryptamine(5-HT) receptor, and interleukin-6(IL-6) to exert
sedative,
anxiolytic, and
antidepressant effects. Sixty 4-week-old SPF mice were randomly divided into a control group, a model group, a positive
drug(
diazepam tablets) group, and low-, medium-, and high-dose
berberine groups. Medication with corresponding drugs was performed for one week. The results demonstrated that
berberine was potent in reducing the activities and standing times of mice, down-regulating the levels of CRP and
IL-6 mRNA in the hypothalamus, and up-regulating the expression of 5-HT(P<0.01); however, no significant effect on ESR1 was observed. The network of Euodiae Fructus in treating
insomnia was constructed by network pharmacology and verified by tests. The findings indicated that the therapeutic efficacy of Euodiae Fructus in treating
insomnia was achieved by participating in multiple biological processes, such as
neurotransmitter receptor activity, which provided a scientific basis for its clinical application.