Baihe Dihuang Tang as a therapeutic candidate for insomnia: Targeting gut dysbiosis and neuroendocrine dysfunction

Baihe Dihuang Tang (BDT), is a traditional Chinese medicinal formulation historically utilized to manage various health conditions, including insomnia. This therapeutic use of BDT for treating insomnia is rooted in its potential to regulate the gut microbiota, neuroendocrine, and serotonin systems, which may collectively contribute to its effectiveness. This study aims to explore the anti-insomnia effects of BDT, and focus on its underlying mechanisms, emphasizing the potential interplay with gut microbiota, neuroendocrine, and serotonin pathways. An insomnia mouse model was induced using p-chlorophenylalanine (PCPA). Subjects received varying doses of BDT or a saline solution as a control. Behavioral assessment was conducted via the open field test and elevated plus maze test. Hypothalamic monoamine neurotransmitter levels were quantified using ELISA kits. Neurosteroid levels in brain and serum samples were determined through high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Gut microbiota composition was evaluated using 16S rRNA amplicon sequencing. PCPA-induced insomnia led to significant alterations in neurosteroids, monoamine neurotransmitters, and gut microbiota composition. BDT treatment markedly improved behavioral parameters in insomniac mice, evidenced by enhanced motility and reduced sleep latency compared to controls. BDT administration restored neurosteroid and monoamine neurotransmitter dose-dependently, suggesting potential for neuroendocrine system homeostasis restoration. BDT-treated mice exhibited significant gut microbiota composition changes, including reduced Acidobacteria, increased Fusobacteria and Firmicutes at the phylum level, and decreased Alistipes at the genus level, compared to the insomnia model group. BDT effectively rectifies gut dysbiosis and mitigates neuroendocrine and serotonin system dysfunctions induced by insomnia, emerging as a promising therapeutic candidate for insomnia management.