Flavonoid Glycosides from Ulmus macrocarpa Inhibit Osteoclast Differentiation via the Downregulation of NFATc1

Abstract

The aim of this study was to isolate and identify chemical components with osteoclast differentiation inhibitory activity from Ulmus macrocarpa Hance bark. Spectroscopic analyses, including nuclear magnetic resonance (NMR) and electronic circular dichroism (ECD), resulted in the unequivocal elucidation of active compounds such as (2S)-naringenin-6-C-beta-D-glucopyranoside (1), (2R)-naringenin-6-C-beta-D-glucopyranoside (2), (2R,3S)-catechin-7-O-beta-D-xylopyranoside (3), (2R,3S)-catechin-7-O-beta-D-apiofuranoside (6), (2R,3R)-taxifolin-6-C-beta-D-glucopyranoside (7), and (2S,3S)-taxifolin-6-C-beta-D-glucopyranoside (8). Mechanistically, the compounds may exhibit osteoclast differentiation inhibitory activity via the downregulation of NFATc1, a master regulator involved in osteoclast formation. This is the first report of their inhibitory activities on the receptor activator of nuclear factor KB ligand (RANKL)-induced osteoclast differentiation in murine bone marrow-derived macrophages. These findings provide further scientific evidence for the rational application of the genus Ulmus for the amelioration or treatment of osteopenic diseases.