{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T09:21:10Z","timestamp":1787822470604,"version":"build-2784847793"},"reference-count":41,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T00:00:00Z","timestamp":1787702400000},"content-version":"vor","delay-in-days":25,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Chem Biol Drug Des"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Triphala is a traditional three\u2010fruit formulation with potential anticancer activity, but its ferroptosis\u2010related mechanisms in oral cancer remain unclear. We integrated network pharmacology, transcriptomic analyses, prognostic modeling, Mendelian randomization, immune and drug\u2010response analyses, molecular docking, and in\u00a0vitro validation to investigate the Triphala\u2013ferroptosis\u2013oral cancer axis. Fifty\u2010eight candidate functional genes were identified, and an eight\u2010gene signature comprising AKR1C3, CA9, EGFR, GSTA1, MAPK8, MGST1, PPARG, and RB1 showed prognostic value across multiple cohorts. Mendelian randomization supported causal associations of MAPK8, MGST1, and PPARG with oral cancer risk. Seven Triphala\u2010derived compounds, including epigallocatechin gallate, quercetin, kaempferol, luteolin, ellagic acid, gallic acid, and quinine, displayed favorable predicted interactions with key targets. In CAL\u201027 cells, Triphala altered the expression of signature genes, reduced GPX4 and SLC7A11 protein levels, increased Fe\n                    <jats:sup>2+<\/jats:sup>\n                    and malondialdehyde, depleted glutathione and glutathione peroxidase activity, and enhanced lipid peroxidation; these effects were partially modulated by ferrostatin\u20101. This study advances the field by linking Triphala to a ferroptosis\u2010based prognostic framework and experimentally demonstrating its regulation of the SLC7A11\u2013GSH\u2013GPX4 axis in oral cancer.\n                  <\/jats:p>","DOI":"10.1111\/cbdd.70375","type":"journal-article","created":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T13:58:47Z","timestamp":1787752727000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Triphala Targets the\n                    <scp>SLC7A11<\/scp>\n                    \u2013\n                    <scp>GSH<\/scp>\n                    \u2013\n                    <scp>GPX4<\/scp>\n                    Axis to Trigger Ferroptosis in Oral Cancer: An Integrated Network Pharmacology, Molecular Docking, and Experimental Validation Study"],"prefix":"10.1111","volume":"108","author":[{"given":"Yiwei","family":"Zhao","sequence":"first","affiliation":[{"name":"Department of Craniomaxillofacial Surgery Leipzig University  Leipzig Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simin","family":"Li","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Cell Biology Beijing Tibetan Hospital, China Tibetology Research Center  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3806-8337","authenticated-orcid":false,"given":"Linxin","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Prosthodontics University of Leipzig  Leipzig Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-3237-6330","authenticated-orcid":false,"given":"Deborah","family":"Kreher","sequence":"additional","affiliation":[{"name":"Department of Conservative Dentistry and Periodontology Brandenburg Medical School (MHB) Theodor Fontane  Brandenburg an der Havel Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6602-377X","authenticated-orcid":false,"given":"Gerhard","family":"Schmalz","sequence":"additional","affiliation":[{"name":"Department of Conservative Dentistry and Periodontology Brandenburg Medical School (MHB) Theodor Fontane  Brandenburg an der Havel Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Fichter","sequence":"additional","affiliation":[{"name":"Department of Craniomaxillofacial Surgery Leipzig University  Leipzig Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3916-6054","authenticated-orcid":false,"given":"Xianda","family":"Hu","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Cell Biology Beijing Tibetan Hospital, China Tibetology Research Center  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,26]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-024-06939-5"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10654-021-00726-8"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/jop.12116"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.4103\/jomfp.jomfp_53_24"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12672-025-03713-7"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1004383"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2025.1688589"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1142\/S0192415X23500271"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2021.08.082"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature24297"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2024.155488"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41580-020-00324-8"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1438807"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-025-07773-z"},{"issue":"11","key":"e_1_2_11_16_1","first-page":"3399","article-title":"Hypoxia\u2010Regulated Carbonic Anhydrase\u20109 (CA9) Relates to Poor Vascularization and Resistance of Squamous Cell Head and Neck Cancer to Chemoradiotherapy","volume":"7","author":"Koukourakis M. 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