{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,19]],"date-time":"2026-07-19T05:20:57Z","timestamp":1784438457265,"version":"3.55.0"},"reference-count":53,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2025,12,6]],"date-time":"2025-12-06T00:00:00Z","timestamp":1764979200000},"content-version":"vor","delay-in-days":5,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Chem Biol Drug Des"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Glioma, a prevalent malignancy globally, presents a serious threat to human health. Recent research has highlighted the significant anti\u2010tumor properties of 6\u2010gingerol (6\u2010G), an active component of the traditional Chinese medicine ginger, though its precise mechanisms in glioma remain to be fully elucidated. This study employed network pharmacology, molecular docking, and dynamic simulation to explore the targets and underlying mechanisms of 6\u2010G's anti\u2010glioma effects, followed by in\u00a0vitro validation of the key pathways. Drug\u2010related targets were identified via PharmMapper and Swiss target prediction databases, while disease\u2010related targets were sourced from GeneCards, OMIM, and TTD. The intersection of these datasets yielded potential therapeutic targets. Subsequent PPI network analysis using STRING11.5 and core gene screening with Cytoscape 3.9.1 led to the construction of a \u201cdrug\u2010target network\u201d and the identification of central genes. GO and KEGG enrichment analyses were conducted on potential therapeutic targets. Molecular docking and dynamic simulations were utilized to analyze the interactions between core genes and 6\u2010G. Ultimately, the primary mechanism underlying 6\u2010G's anti\u2010GC effects was validated through in\u00a0vitro experiments. A total of 183 potential targets for 6\u2010G treatment of glioma were identified, with PPI analysis and core target screening revealing 10 critical targets. Enrichment analyses underscored the PI3K\/AKT pathway as the primary signaling mechanism through which 6\u2010G exerts its therapeutic effects. Molecular docking results showed that AKT1, HSP90AA1, EGFR, and MAPK3 were the key targets of 6\u2010G in the treatment of glioma, and dynamic simulations further verified these findings. In\u00a0vitro findings demonstrated that 6\u2010G effectively inhibits the proliferation of U87 and U251 glioma cells, induces apoptosis, arrests the G1 phase of the cell cycle, and suppresses migration and invasion. Western blot analysis confirmed a significant downregulation of p\u2010AKT in the PI3K\/AKT pathway. In conclusion, 6\u2010G impairs glioma cell proliferation, promotes apoptosis, induces G1 phase arrest, and inhibits migration and invasion, primarily through the suppression of the PI3K\u2010AKT pathway. This finding provides a robust foundation for further research and clinical application.<\/jats:p>","DOI":"10.1111\/cbdd.70217","type":"journal-article","created":{"date-parts":[[2025,12,6]],"date-time":"2025-12-06T08:55:26Z","timestamp":1765011326000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Therapeutic Potential of 6\u2010Gingerol in Glioma: Mechanistic Insights and Experimental Validation"],"prefix":"10.1111","volume":"106","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-0972-8633","authenticated-orcid":false,"given":"Shan","family":"Miao","sequence":"first","affiliation":[{"name":"Department of Pharmacy, Xijing Hospital Fourth Military Medical University  Xi'an China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3157-5715","authenticated-orcid":false,"given":"Wei","family":"Hua","sequence":"additional","affiliation":[{"name":"Department of Obstetrics 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