{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T08:29:07Z","timestamp":1787646547488,"version":"build-2736575974"},"reference-count":55,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T00:00:00Z","timestamp":1787616000000},"content-version":"vor","delay-in-days":236,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"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":["Mediators of Inflammation"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Triptolide demonstrates potent antiarthritic effects in rheumatoid arthritis (RA), although its complete mechanism is not fully elucidated. This study aimed to systematically identify its core targets and regulatory pathways by integrating network pharmacology, molecular docking, and experimental validation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Potential targets of triptolide and RA\u2010associated genes were sourced from public databases. Network module analysis identified key targets, the binding affinity of which to triptolide was subsequently assessed by molecular docking, molecular dynamics (MD) simulations, and drug affinity responsive target stability (DARTS) assay. The functional effects of triptolide on RA fibroblast\u2010like synoviocytes (RA\u2010FLS) behavior, joint inflammation, and bone erosion were further investigated using in vitro cellular assays and a collagen\u2010induced arthritis (CIA) mouse model.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Our analysis identified 73 candidate targets for triptolide against RA, which were primarily enriched in biological processes such as transcription factor activity and inflammatory response. Protein\u2013protein interaction (PPI) network analysis highlighted a core module of five genes, among which STAT3 and its upstream regulator NR1D1 were selected for subsequent investigation. Molecular docking, MD simulation, and DARTS assay confirmed the high\u2010affinity and direct binding of triptolide to NR1D1. In vitro, triptolide effectively suppressed RA\u2010FLS migration and invasion, upregulated NR1D1, and inhibited JAK1\/STAT3 signaling. In vivo, triptolide administration ameliorated arthritis severity and reduced bone erosion in CIA mice, as well as modulation of the NR1D1\/STAT3 axis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This study demonstrates that triptolide alleviates RA through NR1D1\u2010mediated inhibition of JAK1\/STAT3 signaling. Our findings elucidate a novel molecular mechanism for triptolide\u2019s antiarthritic effects, thereby revealing the NR1D1\/JAK1\/STAT3 axis as a potential therapeutic target for RA.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1155\/mi\/3971886","type":"journal-article","created":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T08:14:15Z","timestamp":1787645655000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["NR1D1\u2010Mediated Suppression of JAK1\/STAT3 Signaling Contributes to the Therapeutic Effects of Triptolide in Rheumatoid 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