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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-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.

SUBMITTER: Wang W

PROVIDER: S-EPMC8851653 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature

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

Wang Weihong W Jeong Chanhyeok C Lee Yongjin Y Park Chanyoon C Oh Eunseok E Park Kyu-Hyung KH Cho Youbin Y Kang Eunmo E Lee JunI J Cho Yeon-Jin YJ Park Jung Han Yoon JHY Son Young-Jin YJ Lee Ki Won KW Kang Heonjoong H

ACS omega 20220131 6

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)-catechi ...[more]

PMID: 35187304

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Project description:Excessive osteoclast-mediated bone resorption is a critical cause of osteoporosis affecting many aging people worldwide. 5'-Methylthioadenosine (MTA) is a natural sulfur-containing nucleoside normally produced in prokaryotes, plants, yeast, and higher eukaryotes via polyamine metabolism. MTA affects various physiological responses particularly the inflammatory pathway in both normal and cancerous cells and modulates the activation of nuclear factor-κB involved in the osteoclastogenesis signalling process. While several studies have reported that natural products possess anti-osteoclastogenesis phenolics and flavonoids, the effect of nucleoside derivatives on osteoclastogenesis remains limited. Therefore, this study aimed to explore the molecular mechanisms by which MTA affects pre-osteoclastic RAW 264.7 cells as a potential alleviation compound for inflammation-mediated bone loss. Osteoclasts were established by incubating RAW264.7 macrophage cells with receptor activator of nuclear factor kappa B ligand (RANKL) and macrophage colony-stimulating factor, the vital cytokines for activation of osteoclast differentiation. Cell viability was measured using MTT assays at 24, 48, and 72 h. The suppressive effect of MTA on RANKL-induced osteoclast differentiation and function was assessed using tartrate-resistant acid phosphatase (TRAP) analysis, qRT-PCR, and pit formation, Western blot, and immunofluorescence assays. MTA showed dose-dependent anti-osteoclastogenic activity by inhibiting TRAP-positive cell and pit formation and reducing essential digestive enzymes, including TRAP, cathepsin K, and matrix metallopeptidase 9. MTA was observed to suppress the osteoclast transduction pathway through (RANKL)-induced nuclear factor kappa-light-chain-enhancer of activated B cells (NFƘB); it attenuated NFƘB-P65 expression and down-regulated cFos proto-oncogene and nuclear factor of activated T cell c1 (NFATc1), the main regulators of osteoclasts. Moreover, the suppression of RANK (the initial receptor triggering several osteoclastogenic transduction pathways) was observed. Thus, this study highlights the potential of MTA as an effective therapeutic compound for restoring bone metabolic disease by inhibiting the RANK-NFATc1 signal pathway.

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

Publications

Flavonoid Glycosides from <i>Ulmus macrocarpa</i> Inhibit Osteoclast Differentiation via the Downregulation of NFATc1.

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