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Icariin (ICA), baohuoside I (BHS) and icaritin (ICT) are three flavonoids obtained from Epimedii Folium that are efficient in facilitating osteogenesis. In this study, an active flavonoid with dual effects of reversing iron overload and promoting osteogenesis was screened based on pharmacokinetics, iron complexation properties and the potential to downregulate iron overload, reversing PMOP. As a result, the <jats:italic>in vivo<\/jats:italic> absorption of three compounds was ICA\u2009&gt;\u2009ICT\u2009&gt;\u2009BHS, while the exposure in muscle and bone was BHS\u2009&gt;\u2009ICT\u2009&gt;\u2009ICA. <jats:italic>In vitro<\/jats:italic> complexation showed that only ICT complexed with Fe (III) at a 1:1 ratio on 3\u2010OH and the ICT\u2013Fe (III) complex (<jats:italic>m<\/jats:italic>\/<jats:italic>z<\/jats:italic> 424.3750) was identified by UPLC\u2013Q\u2010TOF\u2013MS. <jats:italic>In vivo<\/jats:italic> dynamic detection also showed that the concentration of ICT\u2013Fe (III) complexes varied with the concentration of ICT in plasma. The behavioral blunting and bone loss in zebrafish induced by Fe (III) were significantly reversed by ICT in a dose\u2010dependent manner. Pharmacokinetic\u2013pharmacodynamic analysis showed that ICT was negatively correlated with serum ferritin and positively correlated with osteogenic markers including alkaline phosphatase, osteocalcin and osteoprotegerin. Bone loss in ovariectomized rats was significantly altered after ICT intervention, with reduced serum ferritin levels and improved osteogenic marker levels. These results demonstrated that ICT had favorable musculoskeletal penetration and iron complexation capability to shrink labile plasma iron, showing superior performance in anti\u2010PMOP through the dual effects of reversing iron overload and promoting osteogenesis.<\/jats:p>","DOI":"10.1002\/bmc.5686","type":"journal-article","created":{"date-parts":[[2023,6,7]],"date-time":"2023-06-07T03:24:07Z","timestamp":1686108247000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Screening of superior anti\u2010osteoporotic flavonoids from Epimedii Folium with dual effects of reversing iron overload and promoting osteogenesis"],"prefix":"10.1002","volume":"37","author":[{"given":"Jun","family":"Jiang","sequence":"first","affiliation":[{"name":"School of Pharmacy Jiangsu University  Zhenjiang Jiangsu Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6532-3295","authenticated-orcid":false,"given":"Jinjin","family":"He","sequence":"additional","affiliation":[{"name":"School of Pharmacy Jiangsu University  Zhenjiang Jiangsu Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shichang","family":"Xiao","sequence":"additional","affiliation":[{"name":"School of Pharmacy Jiangsu University  Zhenjiang Jiangsu Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiayi","family":"Shenyuan","sequence":"additional","affiliation":[{"name":"School of Pharmacy Jiangsu University  Zhenjiang Jiangsu Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tong","family":"Chen","sequence":"additional","affiliation":[{"name":"Comprehensive Technical Center Zhenjiang Customs District P. 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