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α-Asarone Attenuates Osteoclastogenesis and Prevents Against Oestrogen-Deficiency Induced Osteoporosis

Osteoporosis (OP) is defined as low bone mineral density which features over activated osteoclasts (OCs) and bone resorption. Targeting excessive OCs activity is thought to be an effective therapeutic approach for OP treatment. α-asarone (ASA), a compound from the traditional Chinese medicinal herb...

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Autores principales: Tian, Hao, Jiang, Tao, Yang, Kai, Ning, Ruonan, Wang, Tianqi, Zhou, Qi, Qian, Niandong, Huang, Ping, Guo, Lei, Jiang, Min, Xi, Xiaobing, Xu, Xing, Deng, Lianfu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8971932/
https://www.ncbi.nlm.nih.gov/pubmed/35370648
http://dx.doi.org/10.3389/fphar.2022.780590
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author Tian, Hao
Jiang, Tao
Yang, Kai
Ning, Ruonan
Wang, Tianqi
Zhou, Qi
Qian, Niandong
Huang, Ping
Guo, Lei
Jiang, Min
Xi, Xiaobing
Xu, Xing
Deng, Lianfu
author_facet Tian, Hao
Jiang, Tao
Yang, Kai
Ning, Ruonan
Wang, Tianqi
Zhou, Qi
Qian, Niandong
Huang, Ping
Guo, Lei
Jiang, Min
Xi, Xiaobing
Xu, Xing
Deng, Lianfu
author_sort Tian, Hao
collection PubMed
description Osteoporosis (OP) is defined as low bone mineral density which features over activated osteoclasts (OCs) and bone resorption. Targeting excessive OCs activity is thought to be an effective therapeutic approach for OP treatment. α-asarone (ASA), a compound from the traditional Chinese medicinal herb Acorus tatarinowii, has been widely used as a therapeutic agent against several diseases such as epilepsy, cough, bronchitis and asthma for many years. Recently, it was reported that ASA-derived lignins which were purified from Acorus tatarinowii root tissues effectively suppressed both RANKL-induced osteoclastogenesis and bone resorption. Besides, a classic Chinese formulation Bajitianwan (BJTW) which consisted of root and rhizome of Acorus tatarinowii Schott also showed positive effects on age-related bone loss. In the present study, we aimed to study the effects of ASA on osteoclastogenesis in vitro and in vivo. As illustrated by TRAP staining, ASA was capable of inhibiting RANKL-induced osteoclastogenesis in a dose-dependent manner, not only at an early-stage, but also in the late-stage. Besides, it also effectively suppressed bone resorption of mature OCs in a pit resorption assay. The formation of F-actin ring during osteoclastogenesis, which was important in OCs bone-resorption, was impaired as well. Subsequent mechanism experiments exposed that ASA inhibited osteoclastogenesis related genes in a time-dependent manner through AKT, p38 and NF-κB, followed by NFATc1/c-fos signaling pathway. Notably, our in vivo study uncovered that ASA was capable of improving the bone microstructure in oestrogen-deficiency induced OP models. Thus, our current work highlighted the important role of an old drug ASA in bone metabolism especially in OCs differentiation. ASA may find its potential as a lead compound to treat excessive OCs activity-induced bone loss diseases and more structure optimization is further needed.
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spelling pubmed-89719322022-04-02 α-Asarone Attenuates Osteoclastogenesis and Prevents Against Oestrogen-Deficiency Induced Osteoporosis Tian, Hao Jiang, Tao Yang, Kai Ning, Ruonan Wang, Tianqi Zhou, Qi Qian, Niandong Huang, Ping Guo, Lei Jiang, Min Xi, Xiaobing Xu, Xing Deng, Lianfu Front Pharmacol Pharmacology Osteoporosis (OP) is defined as low bone mineral density which features over activated osteoclasts (OCs) and bone resorption. Targeting excessive OCs activity is thought to be an effective therapeutic approach for OP treatment. α-asarone (ASA), a compound from the traditional Chinese medicinal herb Acorus tatarinowii, has been widely used as a therapeutic agent against several diseases such as epilepsy, cough, bronchitis and asthma for many years. Recently, it was reported that ASA-derived lignins which were purified from Acorus tatarinowii root tissues effectively suppressed both RANKL-induced osteoclastogenesis and bone resorption. Besides, a classic Chinese formulation Bajitianwan (BJTW) which consisted of root and rhizome of Acorus tatarinowii Schott also showed positive effects on age-related bone loss. In the present study, we aimed to study the effects of ASA on osteoclastogenesis in vitro and in vivo. As illustrated by TRAP staining, ASA was capable of inhibiting RANKL-induced osteoclastogenesis in a dose-dependent manner, not only at an early-stage, but also in the late-stage. Besides, it also effectively suppressed bone resorption of mature OCs in a pit resorption assay. The formation of F-actin ring during osteoclastogenesis, which was important in OCs bone-resorption, was impaired as well. Subsequent mechanism experiments exposed that ASA inhibited osteoclastogenesis related genes in a time-dependent manner through AKT, p38 and NF-κB, followed by NFATc1/c-fos signaling pathway. Notably, our in vivo study uncovered that ASA was capable of improving the bone microstructure in oestrogen-deficiency induced OP models. Thus, our current work highlighted the important role of an old drug ASA in bone metabolism especially in OCs differentiation. ASA may find its potential as a lead compound to treat excessive OCs activity-induced bone loss diseases and more structure optimization is further needed. Frontiers Media S.A. 2022-03-18 /pmc/articles/PMC8971932/ /pubmed/35370648 http://dx.doi.org/10.3389/fphar.2022.780590 Text en Copyright © 2022 Tian, Jiang, Yang, Ning, Wang, Zhou, Qian, Huang, Guo, Jiang, Xi, Xu and Deng. 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
Tian, Hao
Jiang, Tao
Yang, Kai
Ning, Ruonan
Wang, Tianqi
Zhou, Qi
Qian, Niandong
Huang, Ping
Guo, Lei
Jiang, Min
Xi, Xiaobing
Xu, Xing
Deng, Lianfu
α-Asarone Attenuates Osteoclastogenesis and Prevents Against Oestrogen-Deficiency Induced Osteoporosis
title α-Asarone Attenuates Osteoclastogenesis and Prevents Against Oestrogen-Deficiency Induced Osteoporosis
title_full α-Asarone Attenuates Osteoclastogenesis and Prevents Against Oestrogen-Deficiency Induced Osteoporosis
title_fullStr α-Asarone Attenuates Osteoclastogenesis and Prevents Against Oestrogen-Deficiency Induced Osteoporosis
title_full_unstemmed α-Asarone Attenuates Osteoclastogenesis and Prevents Against Oestrogen-Deficiency Induced Osteoporosis
title_short α-Asarone Attenuates Osteoclastogenesis and Prevents Against Oestrogen-Deficiency Induced Osteoporosis
title_sort α-asarone attenuates osteoclastogenesis and prevents against oestrogen-deficiency induced osteoporosis
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8971932/
https://www.ncbi.nlm.nih.gov/pubmed/35370648
http://dx.doi.org/10.3389/fphar.2022.780590
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