{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T01:26:13Z","timestamp":1792718773377,"version":"4.5.0"},"reference-count":51,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,25]],"date-time":"2026-05-25T00:00:00Z","timestamp":1779667200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Piceatannol (PIC) exhibits antioxidant and anti-inflammatory activities. This study integrates network pharmacology and experimental validation to investigate its potential role in rheumatoid arthritis (RA).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>PIC targets were predicted using public databases. RA-related differentially expressed genes (DEGs) were identified from Gene Expression Omnibus (GEO) datasets (|logFC| \u2265 1 and P-value &amp;lt; 0.05). Intersection genes were analyzed via protein-protein interaction (PPI) network (hub gene selection), molecular docking (binding affinity &amp;lt; -5.0 kcal\/mol as threshold), ConnectivityMap and molecular dynamics simulation. Experimental validation included CCK8, flow cytometry, real-time quantitative PCR (RT-qPCR), Western blotting, and an adjuvant-induced arthritis (AIA) rat model.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      35 intersecting genes were identified, from which 6 hub genes (SYK, CXCL8, TNF, NFKB1, PPARG, and CASP8) were selected. PIC showed stable binding to all hub genes (affinities: -5.6 to -7.8 kcal\/mol). ConnectivityMap suggested a regulatory relationship between PIC and SYK. Molecular dynamics simulations demonstrate that the PIC\u2013SYK complex maintains stable structural integrity. Experimental validation showed that PIC reduced MH7A cell viability, induced G2\/M arrest and apoptosis, and downregulated mRNA levels of SYK, NFKB1, and CASP8, consistent with predictions.\n                      <jats:italic>In vivo<\/jats:italic>\n                      , PIC alleviated AIA severity.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>These preliminary findings suggest that PIC exerts therapeutic effects in RA models, potentially via SYK\/NFKB1\/CASP8. The study provides a theoretical basis for further evaluation of PIC in RA, while acknowledging the exploratory nature of network pharmacology and preclinical models.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1804844","type":"journal-article","created":{"date-parts":[[2026,5,25]],"date-time":"2026-05-25T06:06:31Z","timestamp":1779689191000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Integrating network pharmacology, molecular docking and experimental verification to explore the therapeutic effect of piceatannol on rheumatoid arthritis"],"prefix":"10.3389","volume":"17","author":[{"given":"Mingyi","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Joint Surgery, Honghui Hospital, Xi\u2019an Jiaotong University","place":["Xi\u2019an, Shaanxi, China"]},{"name":"Xi\u2019an Key Laboratory of Pathogenesis and Precision Treatment of Arthritis","place":["Xi\u2019an, 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