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

Weihong Wang; Chanhyeok Jeong; Yongjin Lee; Chanyoon Park; Eunseok Oh; Kyu-Hyung Park; Youbin Cho; Eunmo Kang; JunI Lee; Yeon-Jin Cho; Jung Han Yoon Park; Young-Jin Son; Ki Won Lee; Heonjoong Kang

doi:10.1021/acsomega.1c05305

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

ACS Omega. 2022 Jan 31;7(6):4840-4849. doi: 10.1021/acsomega.1c05305. eCollection 2022 Feb 15.

Authors

Weihong Wang^{1

2}, Chanhyeok Jeong³, Yongjin Lee⁴, Chanyoon Park^{1

5}, Eunseok Oh¹, Kyu-Hyung Park¹, Youbin Cho¹, Eunmo Kang¹, JunI Lee¹, Yeon-Jin Cho⁶, Jung Han Yoon Park^{3

7}, Young-Jin Son⁴, Ki Won Lee^{3

6

7}, Heonjoong Kang^{1

2

5

6}

Affiliations

¹ Laboratory of Marine Drugs, School of Earth and Environmental Sciences, Seoul National University, Seoul 08826, Korea.
² Research Institute of Oceanography, Seoul National University, NS-80, Seoul 08826, Korea.
³ Department of Agricultural Biotechnology and Research Institute of Agriculture and Life Sciences, Seoul National University, Seoul 08826, Korea.
⁴ Department of Pharmacy, Sunchon National University, 315 Maegok-dong, Suncheon, Jeollanam-do 57922, Korea.
⁵ Interdisciplinary Graduate Program in Genetic Engineering, Seoul National University, NS-80, Seoul 08826, Korea.
⁶ Bio-MAX Institute, Seoul National University, Seoul 08826, Korea.
⁷ Advanced Institutes of Convergence Technology, Seoul National University, Suwon 16229, Korea.

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-β-d-glucopyranoside (1), (2R)-naringenin-6-C-β-d-glucopyranoside (2), (2R,3S)-catechin-7-O-β-d-xylopyranoside (3), (2R,3S)-catechin-7-O-β-d-apiofuranoside (6), (2R,3R)-taxifolin-6-C-β-d-glucopyranoside (7), and (2S,3S)-taxifolin-6-C-β-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 κB 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.