{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,16]],"date-time":"2026-05-16T09:18:21Z","timestamp":1778923101592,"version":"3.51.4"},"reference-count":48,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,4,27]],"date-time":"2026-04-27T00:00:00Z","timestamp":1777248000000},"content-version":"vor","delay-in-days":26,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"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":[[2026,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Osteoarthritis (OA), the most prevalent form of arthritis globally, is characterized by debilitating pain driven by inflammatory and degenerative processes in chondrocytes. Here, we demonstrate that arctigenin (ATG), a bioactive lignan from\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>Arctium lappa<\/jats:italic>\n                    <\/jats:styled-content>\n                    , alleviates OA pain by suppressing chondrocyte pyroptosis through the POU Class 2 Homeobox\u00a01 (POU2F1)\/growth factor receptor Bound Protein 10 (GRB10) signaling axis. In a monosodium iodoacetate (MIA)\u2010induced OA rat model, ATG administration reduced pain hypersensitivity, lowered pro\u2010inflammatory cytokines, and elevated anti\u2010inflammatory interleukin\u201010 (IL\u201010), while diminishing expression of pyroptosis effectors including cleaved caspase\u20101, Gasdermin\u2010D\u2010N (GSDMD\u2010N), and NOD\u2010like receptor thermal protein domain associated protein 3 (NLRP3). In\u00a0vitro studies in C28\/I2 chondrocytes revealed that ATG dose\u2010dependently attenuated inflammation and pyroptosis markers. Mechanistically, ATG upregulated POU2F1, a transcription factor that directly binds and activates the GRB10 promoter, as confirmed by enrichment and binding assays. Silencing POU2F1 or GRB10 reversed ATG's inhibitory effects on pyroptosis. In\u00a0vivo validation further showed that ATG's pain\u2010relieving effects in OA rats depend on this axis to curb chondrocyte pyroptosis. Collectively, these findings highlight ATG's potential as a novel analgesic agent for OA by targeting pyroptotic pathways, offering insights into inflammation\u2010driven pain mechanisms.\n                  <\/jats:p>","DOI":"10.1111\/cbdd.70300","type":"journal-article","created":{"date-parts":[[2026,4,27]],"date-time":"2026-04-27T10:58:57Z","timestamp":1777287537000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Preliminary Study on the Mechanism of Arctigenin in Alleviating Osteoarthritis Pain by Suppressing Chondrocyte Pyroptosis: The Potential Role of the\n                    <scp>POU2F1<\/scp>\n                    \/\n                    <scp>GRB10<\/scp>\n                    Axis"],"prefix":"10.1111","volume":"107","author":[{"given":"Tian\u2010Jun","family":"Zhai","sequence":"first","affiliation":[{"name":"School of Acupuncture and Tuina (School of Rehabilitation Medicine) Anhui University of Chinese Medicine  Anhui China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"Feng","sequence":"additional","affiliation":[{"name":"Department of Clinical Investigation Center The Second Rehabilitation Hospital of Shanghai  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cheng\u2010Cheng","family":"Zhu","sequence":"additional","affiliation":[{"name":"School of Acupuncture and Tuina (School of Rehabilitation Medicine) Anhui University of Chinese Medicine  Anhui China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ye\u2010Ping","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Clinical Investigation Center The Second Rehabilitation Hospital of Shanghai  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-4206-8441","authenticated-orcid":false,"given":"Hui","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of 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