{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T19:22:44Z","timestamp":1792092164095,"version":"4.4.0"},"reference-count":47,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T00:00:00Z","timestamp":1773360000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T00:00:00Z","timestamp":1773360000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100007834","name":"Natural Science Foundation of Ningbo Municipality","doi-asserted-by":"publisher","award":["2024J270"],"award-info":[{"award-number":["2024J270"]}],"id":[{"id":"10.13039\/100007834","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Phytotherapy Research"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>As a widespread chronic degenerative joint disease that predominantly affects elderly populations worldwide, osteoarthritis (OA) is pathologically defined by the gradual breakdown of extracellular matrix (ECM), cellular apoptosis, and inflammatory processes. Asperuloside (ASP), an iridoid glycoside compound, demonstrates broad bioactivity encompassing inflammation modulation and oxidative stress mitigation across disease models. Nevertheless, the potential of ASP for OA treatment and its associated molecular mechanisms have not yet been completely deciphered. This investigation sought to clarify the therapeutic mechanisms of ASP in OA, thus providing experimental evidence supporting its potential as a novel disease\u2010modifying treatment. Western blotting and immunofluorescent assay were utilized to explore ASP's protective role against IL\u20101\u03b2\u2010mediated damage in primary chondrocytes in\u00a0vitro. Healing effect of ASP was evaluated via micro\u2010CT imaging, histopathological analysis and immunohistochemical staining were conducted using a rat model with destabilized medial meniscus (DMM) in\u00a0vivo. ASP reversed IL\u20101\u03b2\u2010induced pathological effects, including ECM degradation, inflammatory mediator secretion, and cellular apoptosis in chondrocytes. In the DMM rat model, ASP attenuated cartilage degeneration. Mechanistically, it suppressed OA progression via Nrf2\/HO\u20101\/NQO1 pathway signaling, suppressing both NF\u2010\u03baB activation and ROS accumulation. ASP alleviated OA progression by inhibiting chondrocyte apoptosis, inflammatory responses, and ECM degradation in both cellular and DMM rat models through Nrf2\u2010mediated suppression of NF\u2010\u03baB signaling. Collectively, ASP may be a promising disease\u2010modifying drug for OA.<\/jats:p>","DOI":"10.1002\/ptr.70289","type":"journal-article","created":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T09:32:56Z","timestamp":1773394376000},"page":"3027-3046","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Asperuloside\u2010Mediated Activation of Nrf2 Inhibits the\n                    <scp>NF<\/scp>\n                    \u2010\n                    <scp>\u03baB<\/scp>\n                    Pathway and Suppresses Osteoarthritis Progression"],"prefix":"10.1002","volume":"40","author":[{"given":"Liang","family":"Zhu","sequence":"first","affiliation":[{"name":"Department of Orthopedics The Second Affiliated Hospital of Wenzhou Medical University  Wenzhou Zhejiang China"},{"name":"Key Laboratory of Orthopedics of Zhejiang Province  Wenzhou Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanting","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Orthopedics The Second Affiliated Hospital of Wenzhou Medical University  Wenzhou Zhejiang China"},{"name":"Key Laboratory of Orthopedics of Zhejiang Province  Wenzhou Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng","family":"Huang","sequence":"additional","affiliation":[{"name":"The 906th Hospital of Joint Logistics Support Force of PLA  Ningbo Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongyi","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Orthopedics The Second Affiliated Hospital of Wenzhou Medical University  Wenzhou Zhejiang China"},{"name":"Key Laboratory of Orthopedics of Zhejiang Province  Wenzhou Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zijian","family":"Yan","sequence":"additional","affiliation":[{"name":"Department of Orthopedics The Second Affiliated Hospital of Wenzhou Medical University  Wenzhou Zhejiang China"},{"name":"Key Laboratory of Orthopedics of Zhejiang Province  Wenzhou Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyun","family":"Pan","sequence":"additional","affiliation":[{"name":"Department of Orthopedics The Second Affiliated Hospital of Wenzhou Medical University  Wenzhou Zhejiang China"},{"name":"Key Laboratory of Orthopedics of Zhejiang Province  Wenzhou Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhikai","family":"Lu","sequence":"additional","affiliation":[{"name":"The 906th Hospital of Joint Logistics Support Force of PLA  Ningbo Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,3,13]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.103.059220"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2020.110452"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2017.07.020"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2023.04.003"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2019.06.011"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0006\u20102952(99)00290\u20107"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2021.103283"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2023.115751"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbi.2021.109512"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells8070734"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/wnan.1780"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev\u2010pharmtox\u2010010818\u2010021856"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.archoralbio.2021.105199"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.2174\/138945007779940061"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2015.01.008"},{"issue":"120","key":"e_1_2_12_17_1","first-page":"57","article-title":"Innate Inflammation and Synovial Macrophages in Osteoarthritis Pathophysiology","volume":"37","author":"Griffin T. M.","year":"2019","journal-title":"Clinical and Experimental Rheumatology"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419\u2010020\u201003341\u20109"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21134777"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2019.112230"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22041742"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms161125943"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2023.110587"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2020.22171"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2021.174044"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2018.09.025"},{"key":"e_1_2_12_27_1","doi-asserted-by":"publisher","DOI":"10.1093\/bmb\/lds038"},{"key":"e_1_2_12_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2017.12.050"},{"key":"e_1_2_12_29_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24065364"},{"key":"e_1_2_12_30_1","doi-asserted-by":"publisher","DOI":"10.1111\/nyas.13407"},{"key":"e_1_2_12_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2017.10.130"},{"key":"e_1_2_12_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2024.103134"},{"key":"e_1_2_12_33_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12016\u2010022\u201008941\u20101"},{"key":"e_1_2_12_34_1","doi-asserted-by":"publisher","DOI":"10.4103\/0976\u20100105.177703"},{"key":"e_1_2_12_35_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2017.00282"},{"key":"e_1_2_12_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2015.12.013"},{"key":"e_1_2_12_37_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells10061462"},{"key":"e_1_2_12_38_1","doi-asserted-by":"publisher","DOI":"10.1080\/03008207.2016.1208655"},{"key":"e_1_2_12_39_1","doi-asserted-by":"publisher","DOI":"10.3390\/ph15081027"},{"key":"e_1_2_12_40_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.17300"},{"key":"e_1_2_12_41_1","doi-asserted-by":"publisher","DOI":"10.1042\/BST20150014"},{"key":"e_1_2_12_42_1","doi-asserted-by":"publisher","DOI":"10.3892\/mmr.2017.8036"},{"key":"e_1_2_12_43_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms241713028"},{"key":"e_1_2_12_44_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2023.1188215"},{"key":"e_1_2_12_45_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13075\u2010022\u201002785\u2010y"},{"key":"e_1_2_12_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbi.2023.110539"},{"key":"e_1_2_12_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2012.08.013"},{"key":"e_1_2_12_48_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20225745"}],"container-title":["Phytotherapy Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ptr.70289","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ptr.70289","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ptr.70289","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T12:23:56Z","timestamp":1788870236000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ptr.70289"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,13]]},"references-count":47,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2026,5]]}},"alternative-id":["10.1002\/ptr.70289"],"URL":"https:\/\/doi.org\/10.1002\/ptr.70289","archive":["Portico"],"relation":{},"ISSN":["0951-418X","1099-1573"],"issn-type":[{"value":"0951-418X","type":"print"},{"value":"1099-1573","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,13]]},"assertion":[{"value":"2025-10-27","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-02-16","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-03-13","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}