Honokiol inhibits gastric cancer via tumor microenvironment modulation: a bioinformatics and single-cell analysis.

Honokiol, a natural polyphenol from Magnolia bark, exhibits antitumor effects in various cancers. This study aimed to elucidate its pharmacological mechanisms in gastric cancer. Active components and their targets were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and SwissTargetPrediction databases. Gastric cancer-related genes were collected from the Comparative Toxicogenomics Database and GeneCards databases. Overlapping targets were analyzed using STRING to construct a protein-protein interaction network. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed using DAVID and visualized using Cytoscape. Thirty-four overlapping targets were identified, with CHUK as a key hub gene. Functional enrichment analysis revealed multiple pathways, including NF-κB signaling. Single-cell analysis confirmed CHUK expression in tumor clusters, and immunohistochemistry validated its downregulation following honokiol treatment. These findings suggest that honokiol exerts multi-target and multi-pathway effects in gastric cancer, with CHUK-mediated inhibition of NF-κB signaling identified as a critical mechanism.