Bioinformatics-Based Investigation of the Mechanisms by which Gastrodia Elata and Dauricine Enhance Hypoxia Adaptation

Gastrodia elata Blume (GE), a renowned traditional Chinese medicine (TCM), has been shown to possess anti-hypoxic properties. However, the primary active components and their specific mechanisms of action remain unclear due to its chemical complexity. To this end, active components of GE were identified from online databases, including dauricine. Potential targets were predicted using SwissTargetPrediction, and hypoxia-related targets were collected from disease databases. The intersection of these targets revealed common candidates. Subsequent protein–protein interaction (PPI) network analysis, gene ontology (GO) enrichment analysis, and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis identified AKT1, AKT2, AKT3, PIK3CA, PIK3CB, and PIK3CD as core targets and key signaling pathways. The binding affinity between these core components and targets was further validated through molecular docking and 100-ns molecular dynamics simulations. Notably, 4-(4'-hydroxybenzyloxy)benzyl methyl ether and 4,4'-dihydroxy dibenzyl ether from GE, along with dauricine, enhance hypoxia adaptation primarily via the PI3K/AKT and HIF-1A signaling pathways. These findings provide scientific evidence for the application of TCM in ameliorating hypoxia-related health issues.