Discovery and optimized extraction of the anti-osteoclastic agent epicatechin-7-O-β-D-apiofuranoside from Ulmus macrocarpa Hance bark

Chanhyeok Jeong; Yeon-Jin Cho; Yongjin Lee; Weihong Wang; Kyu-Hyung Park; Eun Roh; Chang Hyung Lee; Young-Jin Son; Jung Han Yoon Park; Heonjoong Kang; Ki Won Lee

doi:10.1038/s41598-023-38208-4

Discovery and optimized extraction of the anti-osteoclastic agent epicatechin-7-O-β-D-apiofuranoside from Ulmus macrocarpa Hance bark

Sci Rep. 2023 Jul 9;13(1):11102. doi: 10.1038/s41598-023-38208-4.

Authors

Chanhyeok Jeong^#¹, Yeon-Jin Cho^#², Yongjin Lee^#³, Weihong Wang^{4

5}, Kyu-Hyung Park⁴, Eun Roh⁴, Chang Hyung Lee², Young-Jin Son³, Jung Han Yoon Park², Heonjoong Kang^{2

4

5

6}, Ki Won Lee^{7

8

9

10

11}

Affiliations

¹ Department of Agricultural Biotechnology and Research Institute of Agriculture and Life Sciences, Seoul National University, Seoul, 08826, Korea.
² Bio-MAX Institute, Seoul National University, Seoul, 08826, Korea.
³ Department of Pharmacy, Sunchon National University, 315 Maegok-dong, Suncheon, Jeollanam-do, 57922, Korea.
⁴ Laboratory of Marine Drugs, School of Earth and Environmental Sciences, Seoul National University, NS-80, Seoul, 08826, Korea.
⁵ Research Institute of Oceanography, Seoul National University, NS-80, Seoul, 08826, Korea.
⁶ Interdisciplinary Graduate Program in Genetic Engineering, Seoul National University, NS-80, Seoul, 08826, Korea.
⁷ Department of Agricultural Biotechnology and Research Institute of Agriculture and Life Sciences, Seoul National University, Seoul, 08826, Korea. [email protected].
⁸ Bio-MAX Institute, Seoul National University, Seoul, 08826, Korea. [email protected].
⁹ Advanced Institutes of Convergence Technology, Seoul National University, Suwon, 16229, Korea. [email protected].
¹⁰ Institutes of Green Bio Science and Technology, Seoul National University, Pyeongchang, 25354, Korea. [email protected].
¹¹ Department of Agricultural Biotechnology and Center for Food and Bio convergence, Seoul National University, Seoul, 08826, Korea. [email protected].

^# Contributed equally.

Abstract

Ulmus macrocarpa Hance bark (UmHb) has been used as a traditional herbal medicine in East Asia for bone concern diseases for a long time. To find a suitable solvent, we, in this study, compared the efficacy of UmHb water extract and ethanol extract which can inhibit osteoclast differentiation. Compared with two ethanol extracts (70% and 100% respectively), hydrothermal extracts of UmHb more effectively inhibited receptor activators of nuclear factor κB ligand-induced osteoclast differentiation in murine bone marrow-derived macrophages. We identified for the first time that (2R,3R)-epicatechin-7-O-β-D-apiofuranoside (E7A) is a specific active compound in UmHb hydrothermal extracts through using LC/MS, HPLC, and NMR techniques. In addition, we confirmed through TRAP assay, pit assay, and PCR assay that E7A is a key compound in inhibiting osteoclast differentiation. The optimized condition to obtain E7A-rich UmHb extract was 100 mL/g, 90 °C, pH 5, and 97 min. At this condition, the content of E7A was 26.05 ± 0.96 mg/g extract. Based on TRAP assay, pit assay, PCR, and western blot, the optimized extract of E7A-rich UmHb demonstrated a greater inhibition of osteoclast differentiation compared to unoptimized. These results suggest that E7A would be a good candidate for the prevention and treatment of osteoporosis-related diseases.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Catechin* / pharmacology
Cell Differentiation
Ethanol / pharmacology
Mice
Osteoclasts
Plant Bark
Plant Extracts / chemistry
Plant Extracts / pharmacology
RANK Ligand / pharmacology
Ulmus*

Substances

Catechin
Plant Extracts
Ethanol
RANK Ligand