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

• Published in: Scientific reports Vol. 13; no. 1; p. 11102
• Main Authors: Jeong, Chanhyeok, Cho, Yeon-Jin, Lee, Yongjin, Wang, Weihong, Park, Kyu-Hyung, Roh, Eun, Lee, Chang Hyung, Son, Young-Jin, Park, Jung Han Yoon, Kang, Heonjoong, Lee, Ki Won
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 09-07-2023; Nature Publishing Group; Nature Portfolio
• Subjects: 631/154; 631/92; Agricultural biotechnology; Animals; Bone marrow; Bones; Catechin - pharmacology; Cell Differentiation; Drug dosages; Epicatechin; Ethanol; Ethanol - pharmacology; Herbal medicine; Humanities and Social Sciences; Liquid chromatography; Macrophages; Mice; multidisciplinary; NMR; Nuclear magnetic resonance; Osteoclastogenesis; Osteoclasts; Osteoporosis; Plant Bark; Plant Extracts - chemistry; Plant Extracts - pharmacology; Polymerase chain reaction; RANK Ligand - pharmacology; Science; Science (multidisciplinary); Ulmus; Ulmus macrocarpa
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-023-38208-4

Ulmus macrocarpa
Hance bark (
Um
Hb) 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
Um
Hb water extract and ethanol extract which can inhibit osteoclast differentiation. Compared with two ethanol extracts (70% and 100% respectively), hydrothermal extracts of
Um
Hb 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
Um
Hb 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
Um
Hb 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
Um
Hb 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.