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Astragaloside IV Protects Detrusor from Partial Bladder Outlet Obstruction-Induced Oxidative Stress by Activating Mitophagy through AMPK-ULK1 Pathway

AIMS: Bladder outlet obstruction (BOO) and the consequent low contractility of detrusor are the leading causes of voiding dysfunction. In this study, we aimed to evaluate the pharmacological activity of astragaloside IV (AS-IV), an antioxidant biomolecule that possess beneficial effect in many organ...

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Autores principales: Zhu, Xiaoyu, Tao, Fangze, Zhang, Li, Yu, Yajie, Xu, Yanchao, Yang, Gang, Wei, Zhifeng, Cheng, Yidong, Yin, Xuelai, Zhang, Xinyuan, Wei, Wu, Wang, Anxi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9300277/
https://www.ncbi.nlm.nih.gov/pubmed/35873803
http://dx.doi.org/10.1155/2022/5757367
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author Zhu, Xiaoyu
Tao, Fangze
Zhang, Li
Yu, Yajie
Xu, Yanchao
Yang, Gang
Wei, Zhifeng
Cheng, Yidong
Yin, Xuelai
Zhang, Xinyuan
Wei, Wu
Wang, Anxi
author_facet Zhu, Xiaoyu
Tao, Fangze
Zhang, Li
Yu, Yajie
Xu, Yanchao
Yang, Gang
Wei, Zhifeng
Cheng, Yidong
Yin, Xuelai
Zhang, Xinyuan
Wei, Wu
Wang, Anxi
author_sort Zhu, Xiaoyu
collection PubMed
description AIMS: Bladder outlet obstruction (BOO) and the consequent low contractility of detrusor are the leading causes of voiding dysfunction. In this study, we aimed to evaluate the pharmacological activity of astragaloside IV (AS-IV), an antioxidant biomolecule that possess beneficial effect in many organs, on detrusor contractility and bladder wall remodeling process. METHODS: Partial BOO (pBOO) was created by urethral occlusion in female rats, followed by oral gavage of different dose of AS-IV or vehicle. Cystometric evaluation and contractility test were performed. Bladder wall sections were used in morphology staining, and bladder tissue lysate was used for ELISA assay. Primary smooth muscle cells (SMCs) derived from detrusor were used for mechanism studies. RESULTS: Seven weeks after pBOO, the bladder compensatory enlarged, and the contractility in response to electrical or chemical stimuli was reduced, while AS-IV treatment reversed this effect dose-dependently. AS-IV also showed beneficial effect on reversing the bladder wall remodeling process, as well as reducing ROS level. In mechanism study, AS-IV activated mitophagy and alleviated oxidative stress via an AMPK-dependent pathway. CONCLUSION: Out data suggested that AS-IV enhanced the contractility of detrusor and protected the bladder from obstruction induced damage, via enhancing the mitophagy and restoring mitochondria function trough an AMPK-dependent way.
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spelling pubmed-93002772022-07-21 Astragaloside IV Protects Detrusor from Partial Bladder Outlet Obstruction-Induced Oxidative Stress by Activating Mitophagy through AMPK-ULK1 Pathway Zhu, Xiaoyu Tao, Fangze Zhang, Li Yu, Yajie Xu, Yanchao Yang, Gang Wei, Zhifeng Cheng, Yidong Yin, Xuelai Zhang, Xinyuan Wei, Wu Wang, Anxi Oxid Med Cell Longev Research Article AIMS: Bladder outlet obstruction (BOO) and the consequent low contractility of detrusor are the leading causes of voiding dysfunction. In this study, we aimed to evaluate the pharmacological activity of astragaloside IV (AS-IV), an antioxidant biomolecule that possess beneficial effect in many organs, on detrusor contractility and bladder wall remodeling process. METHODS: Partial BOO (pBOO) was created by urethral occlusion in female rats, followed by oral gavage of different dose of AS-IV or vehicle. Cystometric evaluation and contractility test were performed. Bladder wall sections were used in morphology staining, and bladder tissue lysate was used for ELISA assay. Primary smooth muscle cells (SMCs) derived from detrusor were used for mechanism studies. RESULTS: Seven weeks after pBOO, the bladder compensatory enlarged, and the contractility in response to electrical or chemical stimuli was reduced, while AS-IV treatment reversed this effect dose-dependently. AS-IV also showed beneficial effect on reversing the bladder wall remodeling process, as well as reducing ROS level. In mechanism study, AS-IV activated mitophagy and alleviated oxidative stress via an AMPK-dependent pathway. CONCLUSION: Out data suggested that AS-IV enhanced the contractility of detrusor and protected the bladder from obstruction induced damage, via enhancing the mitophagy and restoring mitochondria function trough an AMPK-dependent way. Hindawi 2022-07-13 /pmc/articles/PMC9300277/ /pubmed/35873803 http://dx.doi.org/10.1155/2022/5757367 Text en Copyright © 2022 Xiaoyu Zhu et al. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Zhu, Xiaoyu
Tao, Fangze
Zhang, Li
Yu, Yajie
Xu, Yanchao
Yang, Gang
Wei, Zhifeng
Cheng, Yidong
Yin, Xuelai
Zhang, Xinyuan
Wei, Wu
Wang, Anxi
Astragaloside IV Protects Detrusor from Partial Bladder Outlet Obstruction-Induced Oxidative Stress by Activating Mitophagy through AMPK-ULK1 Pathway
title Astragaloside IV Protects Detrusor from Partial Bladder Outlet Obstruction-Induced Oxidative Stress by Activating Mitophagy through AMPK-ULK1 Pathway
title_full Astragaloside IV Protects Detrusor from Partial Bladder Outlet Obstruction-Induced Oxidative Stress by Activating Mitophagy through AMPK-ULK1 Pathway
title_fullStr Astragaloside IV Protects Detrusor from Partial Bladder Outlet Obstruction-Induced Oxidative Stress by Activating Mitophagy through AMPK-ULK1 Pathway
title_full_unstemmed Astragaloside IV Protects Detrusor from Partial Bladder Outlet Obstruction-Induced Oxidative Stress by Activating Mitophagy through AMPK-ULK1 Pathway
title_short Astragaloside IV Protects Detrusor from Partial Bladder Outlet Obstruction-Induced Oxidative Stress by Activating Mitophagy through AMPK-ULK1 Pathway
title_sort astragaloside iv protects detrusor from partial bladder outlet obstruction-induced oxidative stress by activating mitophagy through ampk-ulk1 pathway
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9300277/
https://www.ncbi.nlm.nih.gov/pubmed/35873803
http://dx.doi.org/10.1155/2022/5757367
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