Network pharmacology and experiment indicated that medicinal food homologous components play important roles in insomnia

Abstract Insomnia refers to a subjective experience where insufficient sleep duration and quality affect daytime social functioning. This study aims to screen bioactive components with medicinal food homologous (MFH), such as quercetin, beta‐sitosterol, kaempferol, stigmasterol, and capsaicin, which can treat insomnia and demonstrate that quercetin acts as a direct inhibitor of insomnia‐related glucosylceramidase and as an insulin receptor tyrosine phosphatase inhibitor in the upstream insulin signaling pathway, affecting insomnia targets in the downstream pathway for the treatment of insomnia, using network pharmacology and cell experiment approaches. The results showed that 703 components in 44 MFH were enriched in 139 metabolic pathways and acted on 210 potential targets of insomnia. The protein–protein interaction network is analyzed by cytoNCA, according to the topological analysis results, quercetin, beta‐sitosterol, kaempferol, stigmasterol, and capsaicin of betweenness ranked in the top 10. Quercetin and glucosylceramidase were shown to directly inhibit insomnia proteins through reverse molecular docking. Quercetin was used to culture and stimulate HepG2 cells to detect tyrosine phosphorylation of key cellular proteins in the insulin signaling pathway, concluding that quercetin inhibits the activity of tyrosine phosphatase in a dose‐dependent manner, activating the insulin signaling pathway, triggering a cascade reaction, and affecting the expression of insomnia targets in the downstream pathway. The molecular docking of tyrosine phosphatase and quercetin revealed that quercetin interacted with it near the catalytic site, thereby inhibiting its interaction with the substrate. Overall, this study facilitates the development of medicinal food homologous, which exerts good pharmacological effects in the treatment of insomnia.