{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,6,3]],"date-time":"2025-06-03T04:07:24Z","timestamp":1748923644360,"version":"3.41.0"},"reference-count":33,"publisher":"Public Library of Science (PLoS)","issue":"6","license":[{"start":{"date-parts":[[2025,6,2]],"date-time":"2025-06-02T00:00:00Z","timestamp":1748822400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100014718","name":"Innovative Research Group Project of the National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82074462"],"award-info":[{"award-number":["82074462"]}],"id":[{"id":"10.13039\/100014718","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:sec id=\"sec024\">\n<jats:title>Context<\/jats:title>\n<jats:p>Alpinetin(APT) is a natural product with anti-inflammatory and antioxidant effects. Iron overload has been recognized in recent years as a new way to exacerbate osteoarthritis.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec025\">\n<jats:title>Objective<\/jats:title>\n<jats:p>This study evaluated the effects of ATP on iron overload related osteoarthritis.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec026\">\n<jats:title>Materials and methods<\/jats:title>\n<jats:p>C57BL\/6J mice were randomly allocated to five groups as follows (n\u2009=\u200910 mice each): (1) sham; (2) destabilized medial meniscus(DMM); (3) DMM\u2009+\u2009ID; (4) DMM\u2009+\u2009ID\u2009+\u2009APT-L (50\u2009mg\/kg APT gavage daily); (5) DMM\u2009+\u2009ID\u2009+\u2009APT-H (100\u2009mg\/kg APT gavage daily). The chondrocytes treated by FAC (100\u03bcM) were used as an in vitro model of iron overload and the effect of APT was observed. Flow cytometry, fluorescence microscopy, Western blot, qRT-PCR and micro-CT were used to detect the mechanism of action of the APT.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec027\">\n<jats:title>Result<\/jats:title>\n<jats:p>Our studies showed that APT improved the viability of chondrocytes induced by iron overload. APT can reduce apoptosis of chondrocytes (19.41\u2009\u00b1\u20092.12% vs. 9.82\u2009\u00b1\u20091.74%). Furthermore, APT was found significantly attenuated ROS accumulation (2.04\u2009\u00b1\u20090.31 vs. 1.44\u2009\u00b1\u20090.15-fold) of chondrocytes through upregulating antioxidant genes NRF2 (1.18\u2009\u00b1\u20090.13 vs. 1.55\u2009\u00b1\u20090.17-fold) and HO-1 (1.27\u2009\u00b1\u20090.15 vs. 1.77\u2009\u00b1\u20090.20-fold). In vivo experiments revealed that APT attenuated cartilage damage (OARSI score 5.75\u2009\u00b1\u20091.32 vs. 3.75\u2009\u00b1\u20090.96) and subchondral bone proliferation in iron overload osteoarthritis mice.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec028\">\n<jats:title>Conclusions<\/jats:title>\n<jats:p>Our results show that APT can attenuate iron overload-induced cartilage damage <jats:italic>in vivo<\/jats:italic> and <jats:italic>in vitro<\/jats:italic> via the NRF2\/HO-1 pathway. We demonstrated for the first time that APT has promising applications in iron overload diseases.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0317930","type":"journal-article","created":{"date-parts":[[2025,6,2]],"date-time":"2025-06-02T17:33:26Z","timestamp":1748885606000},"page":"e0317930","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Alpinetin protects against iron overload related osteoarthritis via NRF2\/HO-1 pathway"],"prefix":"10.1371","volume":"20","author":[{"given":"Dongling","family":"Cai","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhaofeng","family":"Pan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shaocong","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qi","family":"He","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Baihao","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miao","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiacong","family":"Xiao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fancheng","family":"Wan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haibin","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1905-9494","authenticated-orcid":true,"given":"Chi","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2025,6,2]]},"reference":[{"key":"pone.0317930.ref001","doi-asserted-by":"crossref","first-page":"16072","DOI":"10.1038\/nrdp.2016.72","article-title":"Osteoarthritis","volume":"2","author":"J Martel-Pelletier","year":"2016","journal-title":"Nat Rev Dis Primers"},{"key":"pone.0317930.ref002","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/j.jot.2020.09.006","article-title":"Chondrocyte ferroptosis contribute to the progression of osteoarthritis","volume":"27","author":"X Yao","year":"2020","journal-title":"J Orthop Translat"},{"issue":"8","key":"pone.0317930.ref003","doi-asserted-by":"crossref","first-page":"635","DOI":"10.7326\/0003-4819-133-8-200010170-00016","article-title":"Osteoarthritis: new insights. 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