Euphoesulatin A prevents osteoclast differentiation and bone loss via inhibiting RANKL-induced ROS production and NF-κB and MAPK signal pathways

• Published in: Bioorganic chemistry 2022-02, Vol.119, p.105511-105511, Article 105511
• Main Authors: Zhang, Yu-ting, Hu, Chen, Zhang, Song-xuan, Zhou, Hui-hao, Xu, Jun, Ma, Jian-da, Dai, Lie, Gu, Qiong
• Format: Article
• Language: English
• Subjects: Animals; Cell Differentiation - drug effects; Cells, Cultured; Dose-Response Relationship, Drug; Euphorbiaceae - chemistry; Jatrophane diterpenoid; MAP Kinase Signaling System - drug effects; Mice; Mice, Inbred C57BL; Molecular Structure; NF-kappa B - metabolism; NFATc1; Osteoclast; Osteoclasts - drug effects; Osteoporosis; Osteoporosis - metabolism; Osteoporosis - prevention & control; RANK Ligand - metabolism; RANKL; Reactive Oxygen Species - metabolism; Structure-Activity Relationship
• ISSN: 0045-2068; 1090-2120
• DOI: 10.1016/j.bioorg.2021.105511

[Display omitted] •Eup A inhibits RANKL-induced osteoclast differentiation and F-actin ring formation.•Eup A prevents NFATc1 activation in RANKL-induced BMM cells.•Eup A inhibits RANKL-induced osteoclasts by attenuating ROS production.•Eup A inhibits RANKL-induced osteoclasts by down-regulation NF-κB and MAPK signaling pathways.•Eup A prevents bone loss and bone turnover increase in OVX mouse. Euphoesulatin A (Eup A), a new jatrophane diterpenoid isolated from the Euphorbia esula L. (Euphorbiaceae), was reported to inhibit RANKL-induced osteoclastogenesis. However, the underlying mechanism and the effect in osteoporosis mouse model are still unclear. This study is the first to demonstrate that Eup A inhibits osteoclastogenesis in vitro and in vivo. Mechanistic analysis suggested that Eup A (3, 6, 12 μM) dose-dependently inhibited osteoclastogenesis by down-regulating the activation of NFATc1 and NF-κB and MAPKs signal pathways. Moreover, Eup A (10 mg/kg) significantly prevented bone loss in ovariectomized mice. This work provides in vitro and in vivo evidence that Eup A could be a potential candidate for the development of anti-osteoporosis agents.