Exploring the Mechanism of Sedative and Hypnotic Effects of Fermented Extract From Acanthopanacis senticosi Radix Et Rhizoma Seu Caulis-Ganoderma applanatum (Pers.) Pat. Through WGCNA Analysis Combined With Network Pharmacology.

Abstract

This study aims to investigate the therapeutic effect of ethanol extract from fermented broth of Acanthopanacis senticosi Radix et Rhizoma seu Caulis-Ganoderma applanatum (EEA-GF) on IM and clarify its active material basis and mechanism of action. Insomnia (IM) model mice were established by induction with p-chlorophenylalanine (PCPA). The IM status was evaluated through a pentobarbital sodium-induced righting reflex test, hematoxylin-eosin (H&E) staining, and biochemical index detection. The composition of EEA-GF and its blood-migrating components were analyzed based on ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) technology. Core active components were screened by combining weighted gene co-expression network analysis (WGCNA), network pharmacology, and molecular docking technology. Animal experiments have shown that EEA-GF exhibits excellent therapeutic efficacy in the treatment of IM. A total of 19 compounds were identified from the serum of mice administered with EEA-GF via gavage using UPLC-MS/MS technology. Through WGCNA, HIF1A, REN, NFE2L2, and PARP1 were determined as core targets. Gene Ontology (GO) enrichment analysis yielded 87 results. In addition to cancer-related pathways, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis mainly included pathways such as the thyroid hormone signaling pathway and neuroactive ligand-receptor interaction. Molecular docking results showed that five components including kaempferol exhibited good binding activity with the aforementioned core targets, indicating that they may be the key material basis for EEA-GF to exert its anti-IM effect. This study is the first to confirm the therapeutic effect of EEA-GF on IM. This finding and the research on its related mechanisms provide a new theoretical basis for the clinical treatment and management of IM, as well as a candidate target with great development prospects.