Isomeric flavonoid aglycones derived from Epimedii Folium exerted different intensities in anti-osteoporosis through OPG/RANKL protein targets

Two Epimedium-derived isomeric flavonoids, CIT and IT, had the therapeutic effect in osteopenic rats. However, it is difficult to expound their activity differences in anti-osteoporosis. This paper contrasted their anti-osteoporosis activity from the perspective of their affinity to OPG/RANKL protein targets. Molecular docking indicated that both of CIT and IT could interact with the hydrophobic pockets of OPG/RANKL, while CIT was easier and more stable to combine with RANKL. On the contrary, compared with CIT, IT was more inclined to combine with OPG and stay away from combining with RANKL. Subsequently, whether the interaction between isomeric flavonoids and OPG/RANKL targets promoted or suppressed bone resorption was undefined and which was validated by zebrafish embryo and ovariectomized rats in this paper. Compared with IT, the staining area and cumulative optical density of zebrafish skeleton were significantly increased after the treatment of CIT (0.1 μM, p