Introduction: This study aimed to explore the underlying pharmacological mechanisms of Jiao-Tai-Wan (JTW) in insomnia. Methods: Network pharmacology approach to explore potential therapeutic targets of JTW in treating insomnia. Molecular docking was conducted to analyze the binding mechanisms of the therapeutic molecules to A2AR. Sleep- deprived model rats were treated by JTW once daily for seven days. Adenosine levels were detected via LC-MS/MS, and A1R and A2AR levels were measured via WB and qPCR. Results: A total of 53 genes were generated. The five target genes with the greatest intersection between JTW and insomnia were ACHE, GSK3B, ADORA2A, MAOA, and APP. GO and KEGG analyses revealed the effects of the hubgenes on signaling pathways involved in neurotransmitter transmission and synaptic structure and function. Molecular docking was conducted on the A2AR. In animal experiments, JTW reduced plasma adenosine concentration and lowered it to physiological levels in the hypothalamus, prefrontal cortex, and brainstem. The A1R level in the BS and the A2AR level in the hippocampus was elevated by JTW in both protein and mRNA patterns. Discussion: We screened potential targets for JTW in the treatment of insomnia using network pharmacology, which included adenosine receptors. Subsequently, we verified the effects of JTW on the adenosine signaling pathway through molecular docking and animal experiments and clarified the regulatory effect of JTW on the adenosine signaling pathway in animal models of insomnia Conclusion: Jiao-Tai-Wan (JTW) ameliorates insomnia through a multi-target mechanism that modulates adenosinergic signaling by reducing elevated adenosine levels and upregulating A1R/A2AR receptor expression.
Lin et al. (Thu,) studied this question.