ABSTRACT
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.
Subject(s)
Euphorbiaceae/chemistry , Osteoclasts/drug effects , Osteoporosis/prevention & control , RANK Ligand/metabolism , Animals , Cell Differentiation/drug effects , Cells, Cultured , Dose-Response Relationship, Drug , MAP Kinase Signaling System/drug effects , Mice , Mice, Inbred C57BL , Molecular Structure , NF-kappa B/metabolism , Osteoporosis/metabolism , Reactive Oxygen Species/metabolism , Structure-Activity RelationshipABSTRACT
Three new cembrane-type diterpenoids, deheiculatins M-O (1-3), together with five known analogues (4-8), were isolated from the twigs of Macaranga pustulata King ex Hook. The structures of new compounds 1-3 were elucidated by extensive spectroscopic analyses, modified Mosher's method, and the experimental and calculated electronic circular dichroism (ECD) experiments. All the isolates were evaluated for their cytotoxicity on three human cancer cell lines (CNE1, CNE2, and HCT 116), and all of them showed weak cytotoxicity (IC50â¯>â¯20⯵M).