Exploring the Therapeutic Targets and Molecular Mechanisms of Astragalus in Lung Cancer by Integrated Computational Analysis.

Previous studies have shown that astragalus may inhibit lung cancer, but its anticancer components and molecular mechanisms have not been fully elucidated. The aim of this study was to identify the primary active components and targets of astragalus against lung cancer through a comprehensive search in authoritative databases. Subsequently, protein--protein interaction, gene ontology, Kyoto Encyclopedia of Genes and Genomes enrichment analyses, and correlation analysis of key targets with lung cancer were performed, and their binding activity was evaluated by molecular docking simulation. The main active components of astragalus against lung cancer were identified as jaranol, quercetin, kaempferol, isomucronulatol, isorhamnetin, methylnissolin, 3,9-di-O-methylnissolin, and 7-O-methylisomucronulatol, which involved seven key targets (CYP19A1, EGFR, SRC, PIK3CA, ABL1, CDK4, and CDK6) and PI3K/AKT-signaling pathway. Further results showed that kaempferol and quercetin had a high binding activity with CDK6 and methylnissolin with PIK3CA. Also, the overexpression of CDK6 and PIK3CA was associated with poor prognosis in lung cancer patients. This study has systematically elucidated the correlation between "astragalus-targets-signaling pathway-lung cancer": kaempferol, methylkinisoline, and quercetin in astragalus may inhibit lung cancer through CDK6-PI3K/AKT-signaling pathway. These compounds are expected to be potential candidates for natural small-molecule anticancer drugs. [ABSTRACT FROM AUTHOR]