Objective To elucidate the potential mechanism of Xiaochaihutang (XCHT) in treating gastroesophageal reflux disease (GERD) with insomnia by using network pharmacology.

Methods The active ingredients and drug targets of Xiaochaihutang, diseases targets of GERD and insomnia were screened through online databases. The intersection of drug targets and disease targets was taken, and the interaction of the intersection targets was analyzed using STRING database. The "active ingredient-target" "drug-active ingredient-common target-disease" and protein-protein interaction (PPI) networks were constructed and analyzed by Cytoscape software. Gene ontology (GO) functional enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed on the intersection targets by the DAVID database. Gene localization of core targets was performed by BioGPS, and the "ingredient-target-pathway-organ/tissue" network was constructed by Cytoscape. AutoDock Vina was used for the molecular docking of main active components with core targets.

Results The main active ingredients of Xiaochaihutang in the treatment of GERD complicated with insomnia included Quercetin, Kaempferol, Baicalein and other ingredients. The key targets included serine/threonine kinase 1(AKT1), interleukin-1B(IL-1B), interleukin-6(IL-6), tumor necrosis factor (TNF), tumor protein 53 (TP53) and so on, which were related to the positive regulation of RNA polymerase Ⅱ promoter transcription, inflammatory response, signal transduction, and other biological processes. The involved pathways included cancer pathway, AGE-RAGE signaling pathway, TNF signaling pathway and MAPK signaling pathway and so on. Key genes were located in the islet, pancreas, pineal gland, thymus and related immune cells. Molecular docking results showed that Quercetin could bind to the core target and exhibit stable conformation.

Conclusion Xiaochaihutang may play a role in the treatment of GERD complicated with insomnia by regulating inflammatory immunity, glucose and lipid metabolism and circadian rhythm.