{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T20:53:30Z","timestamp":1784753610819,"version":"3.55.0"},"reference-count":54,"publisher":"Public Library of Science (PLoS)","issue":"10","license":[{"start":{"date-parts":[[2024,10,31]],"date-time":"2024-10-31T00:00:00Z","timestamp":1730332800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100017691","name":"Guangxi Key Research and Development Plan","doi-asserted-by":"crossref","award":["GuiKe AB22035014"],"award-info":[{"award-number":["GuiKe AB22035014"]}],"id":[{"id":"10.13039\/501100017691","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Background<\/jats:title>\n<jats:p>Osteoarthritis (OA) is featured as cartilage loss, joint pain and loss of labor, which the inflammatory reaction may play critical roles. Ononin is an isoflavone isolating from medicinal plants and has anti-inflammatory effects. Our study investigated the anti-inflammation response of ononin on OA.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Methods<\/jats:title>\n<jats:p>Anterior cruciate ligament transection (ACLT)\u2013induced OA operation was used to establish research model, then treated with ononin for 8 weeks. The condition of joint injury was assessed using pathological staining. The concentration of tumor necrosis factor-\u03b1 (TNF-\u03b1), interleukin-1\u03b2 (IL-1\u03b2) and interleukin-6 (IL-6) in serum were measured by Elisa kit. The expression of collagen II and matrix metalloproteinase 13 (MMP-13) proteins to assess cartilage metabolism level by immunohistochemistry and Western blot. We detected the expression of proteins involved in the MAPK and NF-\u03baB signaling pathways. Finally, we used molecular docking to assess the affinity of ononin for the target proteins ERK1\/2, JNK1\/2, p38 and p65.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Results<\/jats:title>\n<jats:p>Our results confirmed that ononin ameliorated cartilage impairment through histopathological analysis by improving the morphological structures and cartilage tidal lines and decreasing Osteoarthritis Research Society International (OARSI) scores in OA rats. Moreover, ononin inhibited the secretion of above factors in OA rats. Furthermore, ononin has been shown to improve cartilage content levels in OA rats. In addition, ononin inhibited the reactivity of MAPK and NF-\u03baB pathways in OA rats. And molecular docking indicated the ligand molecules could stably bind to the proteins of above receptors.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Conclusion<\/jats:title>\n<jats:p>Our results demonstrated that ononin may ameliorate cartilage damage and inflammatory response in OA rats by downgrading MAPK and NF-\u03baB pathways, thus identifying ononin as a potential novel drug to treat OA.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0310293","type":"journal-article","created":{"date-parts":[[2024,10,31]],"date-time":"2024-10-31T17:27:57Z","timestamp":1730395677000},"page":"e0310293","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":7,"title":["Ononin delays the development of osteoarthritis by down-regulating MAPK and NF-\u03baB pathways in rat models"],"prefix":"10.1371","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4614-9279","authenticated-orcid":true,"given":"Fang","family":"Xu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhaocong","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yueming","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting","family":"Liao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2619-1656","authenticated-orcid":true,"given":"Michael","family":"Aschner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-7190-6469","authenticated-orcid":true,"given":"Qingjun","family":"Wei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2024,10,31]]},"reference":[{"key":"pone.0310293.ref001","first-page":"477","article-title":"Articular cartilage: tissue design and chondrocyte-matrix interactions.","volume":"47","author":"JA Buckwalter","year":"1998","journal-title":"Instructional course lectures."},{"issue":"4","key":"pone.0310293.ref002","doi-asserted-by":"crossref","first-page":"597","DOI":"10.3899\/jrheum.181284","article-title":"Effect of osteoarthritis on work participation and loss of working life-years","volume":"47","author":"T Kontio","year":"2020","journal-title":"The Journal of rheumatology"},{"issue":"5","key":"pone.0310293.ref003","first-page":"510","article-title":"[Non-pharmacological treatments for osteoarthritis: unavoidable and essential].","volume":"69","author":"Y Henrotin","year":"2019","journal-title":"La Revue du praticien."},{"issue":"5","key":"pone.0310293.ref004","first-page":"515","article-title":"[Pharmacological treatments of knee osteoarthritis].","volume":"69","author":"F Eymard","year":"2019","journal-title":"La Revue du praticien."},{"issue":"2","key":"pone.0310293.ref005","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1007\/s10067-018-4270-4","article-title":"Osteoarthritis: a call for research on central pain mechanism and personalized prevention strategies.","volume":"38","author":"JH Villafa\u00f1e","year":"2019","journal-title":"Clinical rheumatology"},{"issue":"4","key":"pone.0310293.ref006","doi-asserted-by":"crossref","first-page":"516","DOI":"10.1016\/j.joca.2021.12.003","article-title":"Association between knee inflammation and knee pain in patients with knee osteoarthritis: a systematic review","volume":"30","author":"P Dainese","year":"2022","journal-title":"Osteoarthritis and cartilage"},{"issue":"2","key":"pone.0310293.ref007","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1007\/s12016-022-08941-1","article-title":"Inflammaging and osteoarthritis.","volume":"64","author":"F Motta","year":"2023","journal-title":"Clinical reviews in allergy & immunology"},{"issue":"1","key":"pone.0310293.ref008","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/j.joca.2012.11.012","article-title":"Osteoarthritis as an inflammatory disease (osteoarthritis is not osteoarthrosis!).","volume":"21","author":"F. 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