Exploring the mechanism of Jiaotai Pill in treating insomnia and erectile dysfunction based on network pharmacology,...

Insomnia and erectile dysfunction (ED) exhibit a closely linked bidirectional association, often forming a vicious cycle. Current treatments focusing on single disorders show limited efficacy for this comorbidity. Jiaotai Pill, a classic traditional Chinese medicine formula, has shown potential in alleviating both conditions, aligning with the principle of "treating different diseases with the same therapy." However, its mechanisms of action remain unclear. This study employed an integrated strategy combining network pharmacology, molecular docking, and molecular dynamics (MD) simulations to systematically explore Jiaotai Pill multi-component, multi-target, and multi-pathway therapeutic mechanisms against comorbid insomnia and ED. First, the active components of Jiaotai Pill and disease-related targets for insomnia and ED were retrieved from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform and relevant disease databases. Subsequently, the overlapping targets between Jiaotai Pill active components and insomnia/ED-related targets were identified. Both protein-protein interaction networks and compound-target networks were constructed based on these overlapping targets. Core targets and active components were further screened via topological analysis of the constructed networks. Gene Ontology functional annotation and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were subsequently performed to explore the biological functions and potential regulatory pathways of the core targets. Finally, molecular docking and MD simulations were carried out to validate and key binding interactions between the screened core active components and their corresponding core targets. A total of 21 potential active components of Jiaotai Pill and 123 overlapping targets between these components and insomnia/ED-related disease targets were successfully identified. AKT1, INS, IL-6, TNF, and TP53 were identified as core targets. Enrichment analysis highlighted TNF, IL-17, and PI3K/Akt signaling pathways. Molecular docking confirmed stable binding affinity, and MD simulations demonstrated high structural stability of the quercetin-AKT1 complex. This study elucidates that Jiaotai Pill may treat comorbid insomnia and ED through multi-component, multi-target, and multi-pathway therapeutic mechanisms.