Screening of superior anti‐osteoporotic flavonoids from Epimedii Folium with dual effects of reversing iron overload and promoting osteogenesis

化学 淫羊藿苷 去卵巢大鼠 体内 内分泌学 药理学 铁蛋白 骨质疏松症 内科学 生物化学 医学 病理 替代医学 生物技术 激素 生物
作者
Jun Jiang,Jinjin He,Shichang Xiao,Jiayi Shenyuan,Tong Chen,Pei Dan
出处
期刊:Biomedical Chromatography [Wiley]
卷期号:37 (9) 被引量:7
标识
DOI:10.1002/bmc.5686
摘要

Iron overload is a risk factor for postmenopausal osteoporosis (PMOP) and lowering iron levels to regulate the labile plasma iron is the preferred therapy. 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 in vivo absorption of three compounds was ICA > ICT > BHS, while the exposure in muscle and bone was BHS > ICT > ICA. In vitro complexation showed that only ICT complexed with Fe (III) at a 1:1 ratio on 3-OH and the ICT-Fe (III) complex (m/z 424.3750) was identified by UPLC-Q-TOF-MS. In vivo dynamic detection also showed that the concentration of ICT-Fe (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-dependent manner. Pharmacokinetic-pharmacodynamic 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-PMOP through the dual effects of reversing iron overload and promoting osteogenesis.
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