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Isolation and Characterization of an Anti-Osteoporotic Compound from Melia toosendan Fructus

Melia toosendan fructus, traditionally employed in traditional Chinese and Korean herbal medicine, exhibits diverse biological properties encompassing anti-tumor, anti-inflammatory, and anti-viral effects. However, its influence on bone metabolism remains largely unexplored. In this study, we invest...

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Autores principales: Kim, Seong Cheol, Gu, Dong Ryun, Yang, Hyun, Lee, Sung-Ju, Ryuk, Jin Ah, Ha, Hyunil
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10609846/
https://www.ncbi.nlm.nih.gov/pubmed/37896213
http://dx.doi.org/10.3390/pharmaceutics15102454
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author Kim, Seong Cheol
Gu, Dong Ryun
Yang, Hyun
Lee, Sung-Ju
Ryuk, Jin Ah
Ha, Hyunil
author_facet Kim, Seong Cheol
Gu, Dong Ryun
Yang, Hyun
Lee, Sung-Ju
Ryuk, Jin Ah
Ha, Hyunil
author_sort Kim, Seong Cheol
collection PubMed
description Melia toosendan fructus, traditionally employed in traditional Chinese and Korean herbal medicine, exhibits diverse biological properties encompassing anti-tumor, anti-inflammatory, and anti-viral effects. However, its influence on bone metabolism remains largely unexplored. In this study, we investigated the impact of an ethanolic extract of Melia toosendan fructus (MTE) on osteoclast differentiation and characterized its principal active constituent in osteoclast differentiation and function, as well as its effects on bone protection. Our findings demonstrate that MTE effectively inhibits the differentiation of osteoclast precursors induced by receptor activator of nuclear factor κB ligand (RANKL). Utilizing a bioassay-guided fractionation approach coupled with UHPLC-MS/MS analysis, we isolated and identified the triterpenoid compound toosendanin (TSN) as the active constituent responsible for MTE’s anti-osteoclastogenic activity. TSN treatment downregulated the expression of nuclear factor of activated T cells c1, a pivotal osteoclastogenic transcription factor, along with molecules implicated in osteoclast-mediated bone resorption, including tumor necrosis factor receptor-associated factor 6, carbonic anhydrase II, integrin beta-3, and cathepsin K. Furthermore, treatment of mature osteoclasts with TSN impaired actin ring formation, acidification, and resorptive function. Consistent with our in vitro findings, TSN administration mitigated trabecular bone loss and reduced serum levels of the bone resorption marker, C-terminal cross-linked telopeptides of type I collagen, in a mouse bone loss model induced by intraperitoneal injections of RANKL. These results suggest that TSN, as the principal active constituent of MTE with inhibitory effects on osteoclastogenesis, exhibits bone-protective properties by suppressing both osteoclast differentiation and function. These findings imply the potential utility of TSN in the treatment of diseases characterized by excessive bone resorption.
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spelling pubmed-106098462023-10-28 Isolation and Characterization of an Anti-Osteoporotic Compound from Melia toosendan Fructus Kim, Seong Cheol Gu, Dong Ryun Yang, Hyun Lee, Sung-Ju Ryuk, Jin Ah Ha, Hyunil Pharmaceutics Article Melia toosendan fructus, traditionally employed in traditional Chinese and Korean herbal medicine, exhibits diverse biological properties encompassing anti-tumor, anti-inflammatory, and anti-viral effects. However, its influence on bone metabolism remains largely unexplored. In this study, we investigated the impact of an ethanolic extract of Melia toosendan fructus (MTE) on osteoclast differentiation and characterized its principal active constituent in osteoclast differentiation and function, as well as its effects on bone protection. Our findings demonstrate that MTE effectively inhibits the differentiation of osteoclast precursors induced by receptor activator of nuclear factor κB ligand (RANKL). Utilizing a bioassay-guided fractionation approach coupled with UHPLC-MS/MS analysis, we isolated and identified the triterpenoid compound toosendanin (TSN) as the active constituent responsible for MTE’s anti-osteoclastogenic activity. TSN treatment downregulated the expression of nuclear factor of activated T cells c1, a pivotal osteoclastogenic transcription factor, along with molecules implicated in osteoclast-mediated bone resorption, including tumor necrosis factor receptor-associated factor 6, carbonic anhydrase II, integrin beta-3, and cathepsin K. Furthermore, treatment of mature osteoclasts with TSN impaired actin ring formation, acidification, and resorptive function. Consistent with our in vitro findings, TSN administration mitigated trabecular bone loss and reduced serum levels of the bone resorption marker, C-terminal cross-linked telopeptides of type I collagen, in a mouse bone loss model induced by intraperitoneal injections of RANKL. These results suggest that TSN, as the principal active constituent of MTE with inhibitory effects on osteoclastogenesis, exhibits bone-protective properties by suppressing both osteoclast differentiation and function. These findings imply the potential utility of TSN in the treatment of diseases characterized by excessive bone resorption. MDPI 2023-10-13 /pmc/articles/PMC10609846/ /pubmed/37896213 http://dx.doi.org/10.3390/pharmaceutics15102454 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Kim, Seong Cheol
Gu, Dong Ryun
Yang, Hyun
Lee, Sung-Ju
Ryuk, Jin Ah
Ha, Hyunil
Isolation and Characterization of an Anti-Osteoporotic Compound from Melia toosendan Fructus
title Isolation and Characterization of an Anti-Osteoporotic Compound from Melia toosendan Fructus
title_full Isolation and Characterization of an Anti-Osteoporotic Compound from Melia toosendan Fructus
title_fullStr Isolation and Characterization of an Anti-Osteoporotic Compound from Melia toosendan Fructus
title_full_unstemmed Isolation and Characterization of an Anti-Osteoporotic Compound from Melia toosendan Fructus
title_short Isolation and Characterization of an Anti-Osteoporotic Compound from Melia toosendan Fructus
title_sort isolation and characterization of an anti-osteoporotic compound from melia toosendan fructus
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10609846/
https://www.ncbi.nlm.nih.gov/pubmed/37896213
http://dx.doi.org/10.3390/pharmaceutics15102454
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