Dauricine Mitigates Hypoxia through Targeting ESR1, PIK3CA, and MTOR: A Network Pharmacology and Molecular Dynamics Simulation Investigation

Hypoxia is a prevalent pathophysiological condition. Prolonged exposure to hypobaric hypoxia can lead to maladaptation, increasing the risk of chronic hypoxic diseases such as high-altitude polycythemia (HAPC). Dauricine, an alkaloid derived from the root of Menispermum dauricum DC, has been demonstrated to possess anti-hypoxic properties; however, its underlying molecular mechanisms remain elusive. In this study, a multi-target molecular mechanism of dauricine in mitigating hypoxia was systematically investigated using an integrated approach combining network pharmacology, molecular docking, and molecular dynamics simulations. Common targets between dauricine and hypoxia-related genes were identified through network pharmacology screening. A protein-protein interaction (PPI) network was constructed to identify core targets, followed by Gene Ontology (GO) functional enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. Molecular docking was subsequently employed to evaluate the binding affinities between dauricine and the core targets, while molecular dynamics simulations were performed to validate the stability of the resulting complexes. Additionally, the drug-likeness and safety profiles of dauricine were assessed. The results indicate that dauricine may exert its anti-hypoxic effects by modulating core targets, including ESR1, PIK3CA, and MTOR, and by acting on key signaling pathways such as PI3K-Akt, MAPK, and mTOR. This study provides a theoretical foundation for the development of dauricine as a multi-target candidate for intervention in hypoxia and establishes a bioinformatics basis for subsequent experimental validation.