{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T05:07:59Z","timestamp":1784092079309,"version":"3.55.0"},"reference-count":58,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T00:00:00Z","timestamp":1784073600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82104164"],"award-info":[{"award-number":["82104164"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Osteoarthritis (OA) is a degenerative musculoskeletal disease characterized by cartilage degradation and inflammation. Sophoridine (SR), a quinolizidine alkaloid from traditional Chinese herbs, has demonstrated anti-inflammatory properties, but its role in OA is unknown.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      The effects of SR on chondrocyte viability were assessed using the Cell Counting Kit-8 (CCK-8) assay. Interleukin-1\u03b2 (IL-1\u03b2)-stimulated murine primary chondrocytes were used as an\n                      <jats:italic>in vitro<\/jats:italic>\n                      OA model. Extracellular matrix (ECM) synthesis was evaluated by toluidine blue staining. Key molecules involved in ECM metabolism, inflammation, and pyroptosis, as well as nuclear factor kappa B (NF-\u03baB) signaling activity, were analyzed using quantitative reverse transcription PCR (RT-qPCR), Western blotting, and immunofluorescence. Chondrocyte morphological changes were examined by scanning electron microscopy. To validate causal mechanisms, a functional rescue experiment was performed\n                      <jats:italic>in vitro<\/jats:italic>\n                      using a specific NF-\u03baB activator. For\n                      <jats:italic>in vivo<\/jats:italic>\n                      studies, an anterior cruciate ligament transection (ACLT)-induced murine OA model was established to evaluate the therapeutic efficacy of SR. OA progression was assessed by functional tests, micro-computed tomography (micro-CT), and histopathological analyses. Immunohistochemistry and immunofluorescence were further performed to evaluate molecular and signaling alterations in cartilage tissues.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      In IL-1\u03b2-stimulated chondrocytes, SR (20 and 40\u00a0\u03bcg\/mL) significantly inhibited ECM degradation and suppressed the expression of pro-inflammatory cytokines.\n                      <jats:italic>In vivo<\/jats:italic>\n                      studies utilizing a well-established murine OA model induced by ACLT demonstrated that intraperitoneal SR administration (7.5 and 15\u00a0mg\/kg\/day for 8 weeks) markedly ameliorated cartilage destruction and inflammation. Notably, SR prominently reduced chondrocyte pyroptosis and suppressed NF-\u03baB pathway activation. Mechanistically, co-treatment with an NF-\u03baB activator significantly reversed the SR-mediated protection of ECM components and abolished the downregulation of key pyroptosis-related proteins.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our study indicates that SR effectively attenuates OA progression, which was associated with the suppression of chondrocyte pyroptosis and inflammation via NF-\u03baB signaling pathway inhibition, suggesting SR as a promising therapeutic agent for OA treatment.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1861567","type":"journal-article","created":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T04:42:33Z","timestamp":1784090553000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Sophoridine attenuates osteoarthritis progression: association with suppression of chondrocyte pyroptosis via inhibiting NF-\u03baB signaling pathway"],"prefix":"10.3389","volume":"17","author":[{"given":"Ludan","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Physiology, College of Basic Medical Sciences, Zhejiang Chinese Medical University","place":["Hangzhou, Zhejiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyu","family":"Xing","sequence":"additional","affiliation":[{"name":"Department of Physiology, College of Basic Medical Sciences, Zhejiang Chinese Medical University","place":["Hangzhou, Zhejiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chengcong","family":"Zhou","sequence":"additional","affiliation":[{"name":"Institute of Orthopaedic and Traumatology, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Traditional Chinese Medicine)","place":["Hangzhou, Zhejiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fangda","family":"Fu","sequence":"additional","affiliation":[{"name":"Institute of Orthopaedic and Traumatology, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Traditional Chinese Medicine)","place":["Hangzhou, Zhejiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zikun","family":"Chen","sequence":"additional","affiliation":[{"name":"Institute of Orthopaedic and Traumatology, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Traditional Chinese Medicine)","place":["Hangzhou, Zhejiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chengliang","family":"Wu","sequence":"additional","affiliation":[{"name":"Institute of Orthopaedic and Traumatology, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Traditional Chinese Medicine)","place":["Hangzhou, Zhejiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongfeng","family":"Ruan","sequence":"additional","affiliation":[{"name":"Institute of Orthopaedic and Traumatology, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Traditional Chinese Medicine)","place":["Hangzhou, Zhejiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming","family":"Yue","sequence":"additional","affiliation":[{"name":"Department of Physiology, College of Basic Medical Sciences, Zhejiang Chinese Medical University","place":["Hangzhou, Zhejiang, China"]},{"name":"Key Laboratory of Blood-stasis-toxin Syndrome of Zhejiang Province, Zhejiang Chinese Medical University","place":["Hangzhou, Zhejiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,15]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1146","DOI":"10.14336\/AD.2019.1127","article-title":"Pyroptosis plays a role in osteoarthritis","volume":"11","author":"An","year":"2020","journal-title":"Aging Dis."},{"key":"B2","doi-asserted-by":"publisher","first-page":"3859","DOI":"10.2147\/jir.s368501","article-title":"Pyroptosis: a novel intervention target in the progression of osteoarthritis","volume":"15","author":"Chang","year":"2022","journal-title":"J. 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