{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T05:18:34Z","timestamp":1783055914628,"version":"3.54.6"},"reference-count":38,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T00:00:00Z","timestamp":1782259200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Inflammatory bowel disease (IBD) poses a significant global health burden with rising incidence, particularly in Asia. This study employed an integrative network pharmacology approach combined with molecular docking to elucidate the therapeutic mechanism of ganoderic acid A (GAA) against IBD. Potential GAA targets were retrieved from pharmacogenomic databases, while IBD-related genes were curated from OMIM and GeneCards databases. Weighted gene co-expression network analysis of IBD transcriptomic datasets (GSE38713, GSE126124) identified disease-associated modules, with the yellow module exhibiting the strongest positive correlation. Functional enrichment analyses demonstrated significant involvement of overlapping targets in lipid metabolism, the inflammatory response, and the mitogen-activated protein kinase (MAPK) signaling cascade pathway. We identified 14 IBD-GAA-ferroptosis-related genes and 54 key module genes. Intersection analysis revealed 5 overlapping targets, including tumor necrosis factor-\u03b1(TNF-\u03b1), peroxisome proliferators-activated receptor \u03b3 (PPAR\u03b3), MAPK14, phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic \u03b1 (PIK3CA), and Caspase 3 (CASP3). Molecular docking confirmed high-affinity binding of GAA to these targets, with binding energies ranging from \u22127.3 to \u221210 kcal\/mol. Crucially, experimental evaluation demonstrated the pivotal role of GAA in alleviating disease pathology. GAA treatment suppressed the significantly elevated levels of TNF-\u03b1 and p-MAPK14 in the organoids using a cytokine\/LPS-induced IBD model. These findings collectively suggest a potential involvement of GAA in pathways associated with ferroptosis regulation, although direct experimental evidence for ferroptosis markers remains to be established. The observed multi-target effects on immune regulation and cellular proliferation\/differentiation provide a foundation for further mechanistic investigation.<\/jats:p>","DOI":"10.3390\/ijms27135698","type":"journal-article","created":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T05:48:16Z","timestamp":1782366496000},"page":"5698","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Exploring the Therapeutic Potential of Ganoderic Acid A Against Inflammatory Bowel Disease Based on Network Pharmacology, Molecular Docking, and Intestinal Organoid Validation"],"prefix":"10.3390","volume":"27","author":[{"given":"Min","family":"Cai","sequence":"first","affiliation":[{"name":"School of Biological and Chemical Engineering, Zhejiang University of Science and Technology, Hangzhou 310023, China"},{"name":"Zhejiang Provincial Key Laboratory for Chemical & Biological Processing Technology of Farm Product, Hangzhou 310023, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manhui","family":"Sun","sequence":"additional","affiliation":[{"name":"School of Biological and Chemical Engineering, Zhejiang University of Science and Technology, Hangzhou 310023, China"},{"name":"Zhejiang Provincial Key Laboratory for Chemical & Biological Processing Technology of Farm Product, Hangzhou 310023, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kecheng","family":"Li","sequence":"additional","affiliation":[{"name":"School of Biological and Chemical Engineering, Zhejiang University of Science and Technology, Hangzhou 310023, China"},{"name":"Zhejiang Provincial Key Laboratory for Chemical & Biological Processing Technology of Farm Product, Hangzhou 310023, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenzhen","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Biological and Chemical Engineering, Zhejiang University of Science and Technology, Hangzhou 310023, China"},{"name":"Zhejiang Provincial Key Laboratory for Chemical & Biological Processing Technology of Farm Product, Hangzhou 310023, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianwei","family":"Mao","sequence":"additional","affiliation":[{"name":"School of Biological and Chemical Engineering, Zhejiang University of Science and Technology, Hangzhou 310023, China"},{"name":"Zhejiang Provincial Key Laboratory for Chemical & Biological Processing Technology of Farm Product, Hangzhou 310023, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3505-1225","authenticated-orcid":false,"given":"Ruyi","family":"Sha","sequence":"additional","affiliation":[{"name":"School of Biological and Chemical Engineering, Zhejiang University of Science and Technology, Hangzhou 310023, China"},{"name":"Zhejiang Provincial Key Laboratory for Chemical & Biological Processing Technology of Farm Product, Hangzhou 310023, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1136\/archdischild-2023-325668","article-title":"Inflammatory bowel disease: Recent developments","volume":"109","author":"Ashton","year":"2024","journal-title":"Arch. 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