{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T06:11:03Z","timestamp":1784268663525,"version":"3.55.0"},"reference-count":45,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T00:00:00Z","timestamp":1784246400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004772","name":"Natural Science Foundation of Ningxia Province","doi-asserted-by":"publisher","award":["2025AAC030782"],"award-info":[{"award-number":["2025AAC030782"]}],"id":[{"id":"10.13039\/501100004772","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004772","name":"Natural Science Foundation of Ningxia Province","doi-asserted-by":"publisher","award":["2025AAC030877"],"award-info":[{"award-number":["2025AAC030877"]}],"id":[{"id":"10.13039\/501100004772","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Bioinform."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Oral lichen planus (OLP) is a chronic inflammatory mucosal disease with a risk of malignant transformation and limited long-term therapeutic options. Paeoniflorin (PF), a natural monoterpene glycoside, exhibits multi-target anti-inflammatory and immunomodulatory properties, but its systematic mechanisms against OLP remain elusive.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We employed an integrative framework combining network pharmacology, transcriptomic cross-validation, molecular docking, and molecular dynamics (MD) simulations. Public databases were mined to identify PF targets and OLP-related genes. Core targets were prioritized via protein-protein interaction (PPI) network topology and further validated using OLP tissue transcriptomic datasets (GSE52130 and GSE213349). Functional enrichment analyses were performed, followed by structural validation of PF\u2013target binding via molecular docking and 100-ns MD simulations.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Sixty-eight overlapping targets between PF and OLP were identified. PPI network analysis and transcriptomic cross-validation pinpointed eight core targets: AKT1, IL6, MMP9, STAT3, TNF, IL1B, PTGS2, and PDE4B. Mechanistically, these targets converged on the TNF, PI3K\u2013Akt, and MAPK signaling pathways, regulating inflammatory response, cell migration, apoptosis, and protease activity at membrane microdomain and extracellular matrix interfaces. Molecular docking showed PF binding affinities comparable to or exceeding reference inhibitors (e.g., STAT3: \u22129.27 vs. Stattic \u22129.16 kcal\/mol). MD simulations confirmed stable conformational binding, with the STAT3 and PDE4B complexes exhibiting the most balanced rigidity and lowest ligand RMSD (0.09\u20130.10 nm).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This study provides a systems-level map of PF\u2019s multi-target intervention in OLP, highlighting a composite anti-inflammatory\u2013immune reprogramming\u2013pro-repair axis centered on core inflammatory kinases and proteases. The structural validation of key targets establishes a mechanistic rationale for PF as a promising therapeutic candidate, warranting further preclinical and clinical development for OLP management.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fbinf.2026.1817487","type":"journal-article","created":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T05:45:37Z","timestamp":1784267137000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Elucidating the molecular mechanisms of paeoniflorin intervention in oral lichen planus: a computational biology and bioinformatics\u2013based research strategy"],"prefix":"10.3389","volume":"6","author":[{"given":"Tian","family":"Zhao","sequence":"first","affiliation":[{"name":"Stomatological Hospital, General Hospital of Ningxia Medical University","place":["Yinchuan, Ningxia, China"]},{"name":"College of Stomatology, Ningxia Medical University","place":["Yinchuan, Ningxia, China"]},{"name":"Ningxia Province Key Laboratory of Oral Diseases Research","place":["Yinchuan, Ningxia, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Chen","sequence":"additional","affiliation":[{"name":"Stomatological Hospital, General Hospital of Ningxia Medical University","place":["Yinchuan, Ningxia, China"]},{"name":"College of Stomatology, Ningxia Medical University","place":["Yinchuan, Ningxia, China"]},{"name":"Ningxia Province Key Laboratory of Oral Diseases Research","place":["Yinchuan, Ningxia, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liang","family":"Yu","sequence":"additional","affiliation":[{"name":"General Hospital of Ningxia Medical University","place":["Yinchuan, Ningxia, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,17]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"i1","DOI":"10.1093\/bioinformatics\/btu304","article-title":"Computational biology and bioinformatics","volume":"30","author":"Batzoglou","year":"2014","journal-title":"Bioinformatics"},{"key":"B2","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1007\/s13659-024-00478-4","article-title":"Paeoniflorin mitigates insulin-like growth factor 1-induced lipogenesis and inflammation in human sebocytes by inhibiting the PI3K\/Akt\/FoxO1 and JAK2\/STAT3 signaling pathways","volume":"14","author":"Cai","year":"2024","journal-title":"Nat. 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