{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T17:41:13Z","timestamp":1793295673458,"version":"4.5.0"},"reference-count":53,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2024,8,27]],"date-time":"2024-08-27T00:00:00Z","timestamp":1724716800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100017594","name":"Medical Science and Technology Project of Zhejiang Province","doi-asserted-by":"publisher","award":["2022KY1430"],"award-info":[{"award-number":["2022KY1430"]}],"id":[{"id":"10.13039\/501100017594","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Phytotherapy Research"],"published-print":{"date-parts":[[2024,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Glucocorticoid\u2010induced osteoporosis (GIOP) commonly accelerates bone loss, increasing the risk of fractures and osteonecrosis more significantly than traditional menopausal osteoporosis. The extracellular environment influenced by glucocorticoids heightens fracture and osteonecrosis risks. Fraxin (Fra), a key component of the traditional Chinese herbal remedy <jats:italic>Cortex Fraxini<\/jats:italic>, is known for its wide\u2010ranging pharmacological effects, but its impact on GIOP remains unexplored. This investigation aims to delineate the effects and underlying mechanisms of Fra in combating dexamethasone (Dex)\u2010induced ferroptosis and GIOP. We established a mouse model of GIOP via intraperitoneal injections of Dex and cultured osteoblasts with Dex treatment for in vitro analysis. We evaluated the impact of Fra on Dex\u2010treated osteoblasts through assays such as C11\u2010BODIPY and FerroOrange staining, mitochondrial functionality tests, and protein expression analyses via Western blot and immunofluorescence. The influence of Fra on bone microarchitecture of GIOP in mice was assessed using microcomputerized tomography, hematoxylin and eosin staining, double\u2010labeling with Calcein\u2013Alizarin Red S, and immunohistochemistry at imaging and histological levels. Based on our data, Fra prevented Dex\u2010induced ferroptosis and bone loss. In vitro, glutathione levels increased and malondialdehyde, lipid peroxidation, and mitochondrial reactive oxygen species decreased. Fra treatment also increases nuclear factor erythroid 2\u2010related factor 2 (Nrf2), glutathione peroxidase 4 (GPX4), and COL1A1 expression and promotes bone formation. To delve deeper into the mechanism, the findings revealed that Fra triggered the activation of Nrf2\/GPX4 signaling. Moreover, the use of siRNA\u2010Nrf2 blocked the beneficial effect of Fra in osteoblasts cultivated with Dex. Fra effectively combats GIOP by activating the Nrf2\/GPX4 signaling pathway to inhibit ferroptosis.<\/jats:p>","DOI":"10.1002\/ptr.8310","type":"journal-article","created":{"date-parts":[[2024,8,28]],"date-time":"2024-08-28T06:45:21Z","timestamp":1724827521000},"page":"5203-5224","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Delay the progression of glucocorticoid\u2010induced osteoporosis: Fraxin targets ferroptosis via the <scp>Nrf2\/GPX4<\/scp> pathway"],"prefix":"10.1002","volume":"38","author":[{"given":"Xiang","family":"Zheng","sequence":"first","affiliation":[{"name":"Department of Orthopedics Lishui Municipal Central Hospital  Lishui Zhejiang China"},{"name":"Department of Orthopedics The Fifth Affiliated Hospital of Wenzhou Medical University  Lishui Zhejiang 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