Discovery of ingenane and jatrophane diterpenoids from Euphorbia esula as inhibitors of RANKL-induced osteoclastogenesis

Abstract

Two new ingenane diterpenoids (1–2), four new jatrophane diterpenoids (3–6), and seven known analogues (7–13), were isolated from the 95% ethanol extract of Euphorbia esula. Their structures were determined by extensive spectroscopic methods and ECD data analysis. These compounds were assayed for their anti-osteoporotic activity in a bone marrow-derived macrophage (BMM) cell line, and compounds 2, 4, 7, 8, 9, and 11 significantly inhibited the formation of osteoclasts with IC50 values of 3.4, 4.3, 2.1, 0.5, 1.5, and 4.5 μM, respectively. These compounds also dose-dependently reduced the activity of nuclear factor activated T-cell cytoplasmic 1 (NFATc1). This study reveals the anti-osteoporotic effects of ingenane diterpenoids for the first time.