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.

Keywords: Diterpenoids; Euphorbia esula; Ingenane; Jatrophane; Osteoporosis.