Journal
BIOORGANIC CHEMISTRY
Volume 119, Issue -, Pages -Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bioorg.2021.105511
Keywords
Jatrophane diterpenoid; Osteoporosis; RANKL; Osteoclast; NFATc1
Funding
- Guangdong Basic and Applied Basic Research Foundation [2019A1515012138]
- National Natural Science Foundation of China [81573310]
- Guangdong Provincial-level Special Funds for Promoting High-quality Economic Development [2020032]
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Euphoesulatin A (Eup A) is a newly discovered compound that inhibits osteoclastogenesis through modulation of multiple signaling pathways, showing potential as a candidate for the development of anti-osteoporosis agents. It has been shown to significantly prevent bone loss in ovariectomized mice, highlighting its therapeutic potential in osteoporosis treatment.
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 mu M) dose-dependently inhibited osteoclastogenesis by down-regulating the activation of NFATc1 and NF-kappa B 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.
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