Jatrophane Diterpenoids from as Inhibitors of RANKL-Induced Osteoclastogenesis.

Eighteen new jatrophane diterpenoids, euphoesulatins A-R (-), and three known diterpenoids (-) were isolated from Compounds -, , and represent a rare type of jatrophane-type diterpenoid containing a nicotinoyloxy group. The absolute configuration of was determined by X-ray crystallography. The compounds were assayed for their antiosteoporotic activity in a bone-marrow-derived macrophage cell line, and compounds , , and significantly inhibited the formation of osteoclasts, with IC values of 1.2, 3.5, and 2.3 μM, respectively. These three compounds also dose-dependently reduced the activity of nuclear factor activated T-cell cytoplasmic 1. This study reveals the antiosteoporotic effects of jatrophane diterpenoids for the first time.