RESUMEN
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.
Asunto(s)
Euphorbiaceae/química , Osteoclastos/efectos de los fármacos , Osteoporosis/prevención & control , Ligando RANK/metabolismo , Animales , Diferenciación Celular/efectos de los fármacos , Células Cultivadas , Relación Dosis-Respuesta a Droga , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Ratones , Ratones Endogámicos C57BL , Estructura Molecular , FN-kappa B/metabolismo , Osteoporosis/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Relación Estructura-ActividadRESUMEN
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).