Abstract:

This study aims to systematically investigate the active components， target genes， and molecular mechanisms of Hyssopus cuspidatus Boriss. in the treatment of asthma， thereby providing a scientific basis for its clinical application. A comprehensive metabolomic analysis of Hyssopus cuspidatus Boriss. was conducted using dual-platform UPLC-MS/MS and GC-MS to identify its active components. Potential therapeutic targets were screened using databases such as TCMSP， PubChem， and SwissTargetPrediction. Asthma-related targets were retrieved from GeneCards， OMIM， and TTD databases. A protein-protein interaction （PPI） network was constructed， followed by Gene Ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） enrichment analyses. Molecular docking was performed to validate the binding affinity between active components and core targets. Finally， a two-sample Mendelian randomization （MR） analysis was employed to verify the causal relationship between core targets and asthma. The results showed that a total of 79 active components and 410 potential targets were identified in Hyssopus cuspidatus Boriss. Intersection with asthma-related targets yielded 76 common targets. PPI network analysis revealed AKT1， STAT3， EGFR， PTGS2， and SRC as core targets. GO and KEGG enrichment analyses indicated significant enrichment in processes such as the PI3K/AKT signaling pathway， inflammatory response， and apoptosis. Molecular docking results demonstrated strong binding affinities between flavonoid components （e.g.， luteolin and isorhamnetin） and core targets. Mendelian randomization analysis further confirmed a significant causal relationship between AKT1 and asthma. Hyssopus cuspidatus Boriss. might exert therapeutic effects on asthma through multiple flavonoid active components targeting core genes such as AKT1， regulating signaling pathways like PI3K/AKT， thereby suppressing airway inflammation and alleviating airway hyperresponsiveness. AKT1 is identified as a key target with potential clinical translational value.

Key words: Hyssopus cuspidatus Boriss., asthma, Mendelian randomization, network pharmacology