Epimedium (EP) is a traditional Chinese medicine that has been used to treat osteoporosis for several years, but its mechanism of action is unclear. We used ultrahigh-performance liquid chromatography coupled with triple-quadrupole mass spectrometry (UPLC-QQQ-MS/MS) to detect the components of raw and processed EP samples. The antioxidant activities of the various tested compounds were evaluated using 1,1-diphenyl-2-trinitrophenylhydrazine (DPPH), and their antiosteoporosis effects were assessed in H2O2-stimulated MC3T3 cells and zebrafish embryos. The correlation between the chemical ingredients and efficacy indicators was determined using Pearson correlation analysis. Furthermore, the efficacy of the active ingredients in treating osteoporosis was verified through the implementation of network pharmacology and the application of molecular docking techniques, providing a more comprehensive understanding of their therapeutic potential. The pharmacologically active ingredients were quercetin, Epimedium B, Baohuoside I, and anhydroicaritin-7-O-glucoside. Moreover, network pharmacology and molecular docking studies demonstrated that the four active components could have antiosteoporosis effects by influencing AKT1 and PTGS2. This study provides a basis for future research on the pharmacokinetics of EP and serves as a useful guide for further exploration of EP.
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