Yongxiang Xu: Department of Pharmacy, Affiliated Dongguan Hospital, Southern Medical University, Dongguan, China.
Shichun Chen: Department of Pharmacy, Affiliated Dongguan Hospital, Southern Medical University, Dongguan, China.
Linxuan Huang: Dongguan Institute of Clinical Cancer Research, Affiliated Dongguan Hospital, Southern Medical University, Dongguan, China.
Weichao Han: Department of Pharmacy, Affiliated Dongguan Hospital, Southern Medical University, Dongguan, China.
Yingying Shao: Department of Pharmacy, Affiliated Dongguan Hospital, Southern Medical University, Dongguan, China.
Minyi Chen: Department of Pharmacy, Affiliated Dongguan Hospital, Southern Medical University, Dongguan, China.
Yusheng Zhang: Department of Pharmacy, The First People's Hospital of Foshan (The Affiliated Foshan Hospital of Sun Yat-Sen University), Foshan, China.
Ruirong He: Department of Pharmacy, Affiliated Dongguan Hospital, Southern Medical University, Dongguan, China.
Baocheng Xie: Department of Pharmacy, Affiliated Dongguan Hospital, Southern Medical University, Dongguan, China.
Secondary osteoporosis is triggered mostly by glucocorticoid (GC) therapy. Dexamethasone (DEX) was reported to inhibit osteogenic differentiation in zebrafish larvae and MC3T3-E1 cells in prior research. In this research, we primarily examined the protective impacts of epimedin C on the osteogenic inhibition impact of MC3T3-E1 cells and zebrafish larvae mediated by DEX. The findings illustrated no apparent toxicity for MC3T3-E1 cells after administering epimedin C at increasing dosages from 1 to 60 μM and no remarkable proliferation in MC3T3-E1 cells treated using DEX. In MC3T3-E1 cells that had been treated using DEX, we discovered that epimedin C enhanced alkaline phosphatase activities and mineralization. Epimedin C could substantially enhance the protein expression of osterix (OSX), Runt-related transcription factor 2 (RUNX2), and alkaline phosphatase (ALPL) in MC3T3-E1 cells subjected to DEX treatment. Additionally, epimedin C stimulated PI3K and AKT signaling pathways in MC3T3-E1 cells that had been treated using DEX. Furthermore, in a zebrafish larvae model, epimedin C was shown to enhance bone mineralization in DEX-mediated bone impairment. We also found that epimedin C enhanced ALPL activity and mineralization in MC3T3-E1 cells treated using DEX, which may be reversed by PI3K inhibitor (LY294002). LY294002 can also reverse the protective impact of epimedin C on DEX-mediated bone impairment in zebrafish larval. These findings suggested that epimedin C alleviated the suppressive impact of DEX on the osteogenesis of zebrafish larval and MC3T3-E1 cells via triggering the PI3K and AKT signaling pathways. Epimedin C has significant potential in the development of innovative drugs for the treatment of glucocorticoid-mediated osteoporosis.
