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A novel Glycyrrhiza glabra extract liquiritin targeting NFATc1 activity and ROS levels to counteract ovariectomy-induced osteoporosis and bone loss in murine model

Osteoporosis, a prevalent osteolytic condition worldwide, necessitates effective strategies to inhibit excessive bone resorption by curbing osteoclast hyperactivation. Liquiritin (LIQ), an flavanone derivative employed in acute lung injury and rheumatoid arthritis treatment, possesses an unclear rol...

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Autores principales: Hong, Guoju, Zhou, Lin, Zheng, Guanqiang, Zheng, Xiaoxia, Chen, Zhenqiu, He, Wei, Wei, Qiushi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10663366/
https://www.ncbi.nlm.nih.gov/pubmed/38026985
http://dx.doi.org/10.3389/fphar.2023.1287827
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author Hong, Guoju
Zhou, Lin
Zheng, Guanqiang
Zheng, Xiaoxia
Chen, Zhenqiu
He, Wei
Wei, Qiushi
author_facet Hong, Guoju
Zhou, Lin
Zheng, Guanqiang
Zheng, Xiaoxia
Chen, Zhenqiu
He, Wei
Wei, Qiushi
author_sort Hong, Guoju
collection PubMed
description Osteoporosis, a prevalent osteolytic condition worldwide, necessitates effective strategies to inhibit excessive bone resorption by curbing osteoclast hyperactivation. Liquiritin (LIQ), an flavanone derivative employed in acute lung injury and rheumatoid arthritis treatment, possesses an unclear role in addressing excessive bone resorption. In this investigation, we found that LIQ demonstrates the ability to inhibit osteoclast formation and the bone-resorbing activity induced by RANKL. At a specific concentration, LIQ significantly attenuated NF-κB-Luc activity induced by RANKL and curtailed NF-κB activation in RANKL-stimulated RAW264.7 cells, resulting in reduced IκB-α breakdown and diminished nuclear NF-κB levels. Furthermore, LIQ markedly inhibited RANKL-induced NFATc1 activation, as evidenced by diminished NFATc1 luciferase activity, reduced NFATc1 mRNA levels, and decreased nuclear NFATc1 protein levels. Subsequent experiments demonstrated that LIQ effectively restrained the RANKL-induced elevation of intracellular calcium as well as reactive oxygen species. Additionally, LIQ exhibited a downregulating effect on the expression of osteoclast-specific genes, which include Acp5, Cathepsin K, Atp6v0d2, Nfatc1, c-Fos, and Mmp9. Notably, our findings revealed the potential of LIQ to counteract decreased bone density in mice that underwent ovariectomy. Collectively, the data indicate that LIQ impedes osteoclast formation triggered by RANKL and the subsequent reduction in bone mass by mitigating ROS levels and suppressing the Ca(2+)/MAPK-NFATc1 signaling pathway, suggesting its promising candidacy as a therapeutic agent for RANKL-mediated osteoporosis.
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spelling pubmed-106633662023-11-08 A novel Glycyrrhiza glabra extract liquiritin targeting NFATc1 activity and ROS levels to counteract ovariectomy-induced osteoporosis and bone loss in murine model Hong, Guoju Zhou, Lin Zheng, Guanqiang Zheng, Xiaoxia Chen, Zhenqiu He, Wei Wei, Qiushi Front Pharmacol Pharmacology Osteoporosis, a prevalent osteolytic condition worldwide, necessitates effective strategies to inhibit excessive bone resorption by curbing osteoclast hyperactivation. Liquiritin (LIQ), an flavanone derivative employed in acute lung injury and rheumatoid arthritis treatment, possesses an unclear role in addressing excessive bone resorption. In this investigation, we found that LIQ demonstrates the ability to inhibit osteoclast formation and the bone-resorbing activity induced by RANKL. At a specific concentration, LIQ significantly attenuated NF-κB-Luc activity induced by RANKL and curtailed NF-κB activation in RANKL-stimulated RAW264.7 cells, resulting in reduced IκB-α breakdown and diminished nuclear NF-κB levels. Furthermore, LIQ markedly inhibited RANKL-induced NFATc1 activation, as evidenced by diminished NFATc1 luciferase activity, reduced NFATc1 mRNA levels, and decreased nuclear NFATc1 protein levels. Subsequent experiments demonstrated that LIQ effectively restrained the RANKL-induced elevation of intracellular calcium as well as reactive oxygen species. Additionally, LIQ exhibited a downregulating effect on the expression of osteoclast-specific genes, which include Acp5, Cathepsin K, Atp6v0d2, Nfatc1, c-Fos, and Mmp9. Notably, our findings revealed the potential of LIQ to counteract decreased bone density in mice that underwent ovariectomy. Collectively, the data indicate that LIQ impedes osteoclast formation triggered by RANKL and the subsequent reduction in bone mass by mitigating ROS levels and suppressing the Ca(2+)/MAPK-NFATc1 signaling pathway, suggesting its promising candidacy as a therapeutic agent for RANKL-mediated osteoporosis. Frontiers Media S.A. 2023-11-08 /pmc/articles/PMC10663366/ /pubmed/38026985 http://dx.doi.org/10.3389/fphar.2023.1287827 Text en Copyright © 2023 Hong, Zhou, Zheng, Zheng, Chen, He and Wei. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Hong, Guoju
Zhou, Lin
Zheng, Guanqiang
Zheng, Xiaoxia
Chen, Zhenqiu
He, Wei
Wei, Qiushi
A novel Glycyrrhiza glabra extract liquiritin targeting NFATc1 activity and ROS levels to counteract ovariectomy-induced osteoporosis and bone loss in murine model
title A novel Glycyrrhiza glabra extract liquiritin targeting NFATc1 activity and ROS levels to counteract ovariectomy-induced osteoporosis and bone loss in murine model
title_full A novel Glycyrrhiza glabra extract liquiritin targeting NFATc1 activity and ROS levels to counteract ovariectomy-induced osteoporosis and bone loss in murine model
title_fullStr A novel Glycyrrhiza glabra extract liquiritin targeting NFATc1 activity and ROS levels to counteract ovariectomy-induced osteoporosis and bone loss in murine model
title_full_unstemmed A novel Glycyrrhiza glabra extract liquiritin targeting NFATc1 activity and ROS levels to counteract ovariectomy-induced osteoporosis and bone loss in murine model
title_short A novel Glycyrrhiza glabra extract liquiritin targeting NFATc1 activity and ROS levels to counteract ovariectomy-induced osteoporosis and bone loss in murine model
title_sort novel glycyrrhiza glabra extract liquiritin targeting nfatc1 activity and ros levels to counteract ovariectomy-induced osteoporosis and bone loss in murine model
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10663366/
https://www.ncbi.nlm.nih.gov/pubmed/38026985
http://dx.doi.org/10.3389/fphar.2023.1287827
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