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Cycloastragenol Confers Cerebral Protection after Subarachnoid Hemorrhage by Suppressing Oxidative Insults and Neuroinflammation via the SIRT1 Signaling Pathway

Subarachnoid hemorrhage (SAH) is an acute cerebral vascular disease featured by oxidative insults and neuroinflammation. Cycloastragenol (CAG), the major active component of Astragalus radix, has a wide range of biological functions. However, the potential beneficial effects and the underlying molec...

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Autores principales: Lin, Weibin, Yao, Hao, Lai, Jinqing, Zeng, Yile, Guo, Xieli, Lin, Shu, Hu, Weipeng, Chen, Junyan, Chen, Xiangrong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9184193/
https://www.ncbi.nlm.nih.gov/pubmed/35693703
http://dx.doi.org/10.1155/2022/3099409
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author Lin, Weibin
Yao, Hao
Lai, Jinqing
Zeng, Yile
Guo, Xieli
Lin, Shu
Hu, Weipeng
Chen, Junyan
Chen, Xiangrong
author_facet Lin, Weibin
Yao, Hao
Lai, Jinqing
Zeng, Yile
Guo, Xieli
Lin, Shu
Hu, Weipeng
Chen, Junyan
Chen, Xiangrong
author_sort Lin, Weibin
collection PubMed
description Subarachnoid hemorrhage (SAH) is an acute cerebral vascular disease featured by oxidative insults and neuroinflammation. Cycloastragenol (CAG), the major active component of Astragalus radix, has a wide range of biological functions. However, the potential beneficial effects and the underlying molecular mechanisms of CAG on SAH remain obscure. In the current study, the cerebroprotective effects and mechanism of CAG on SAH were evaluated both in vivo and in vitro. Our results indicated that CAG significantly suppressed SAH-triggered oxidative insults, inflammatory mediators production, microglia activation, and the neutrophil infiltration in the brain. In addition, CAG improved neurological function and ameliorated neuronal apoptosis and degeneration after SAH. In vitro results also revealed the therapeutic effects of CAG on neurons and microglia co-culture system. Mechanistically, CAG treatment upregulated sirtuin 1 (SIRT1) expression, inhibited the levels of FoxO1, nuclear factor-kappa B, and p53 acetylation, and suppressed the subsequent oxidative, inflammatory, and apoptotic pathways. In contrast, inhibiting SIRT1 by pretreatment with Ex527 abrogated the protective actions of CAG both in vivo and in vitro models of SAH. Collectively, our findings indicated that CAG could be a promising and effective drug candidate for SAH.
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spelling pubmed-91841932022-06-10 Cycloastragenol Confers Cerebral Protection after Subarachnoid Hemorrhage by Suppressing Oxidative Insults and Neuroinflammation via the SIRT1 Signaling Pathway Lin, Weibin Yao, Hao Lai, Jinqing Zeng, Yile Guo, Xieli Lin, Shu Hu, Weipeng Chen, Junyan Chen, Xiangrong Oxid Med Cell Longev Research Article Subarachnoid hemorrhage (SAH) is an acute cerebral vascular disease featured by oxidative insults and neuroinflammation. Cycloastragenol (CAG), the major active component of Astragalus radix, has a wide range of biological functions. However, the potential beneficial effects and the underlying molecular mechanisms of CAG on SAH remain obscure. In the current study, the cerebroprotective effects and mechanism of CAG on SAH were evaluated both in vivo and in vitro. Our results indicated that CAG significantly suppressed SAH-triggered oxidative insults, inflammatory mediators production, microglia activation, and the neutrophil infiltration in the brain. In addition, CAG improved neurological function and ameliorated neuronal apoptosis and degeneration after SAH. In vitro results also revealed the therapeutic effects of CAG on neurons and microglia co-culture system. Mechanistically, CAG treatment upregulated sirtuin 1 (SIRT1) expression, inhibited the levels of FoxO1, nuclear factor-kappa B, and p53 acetylation, and suppressed the subsequent oxidative, inflammatory, and apoptotic pathways. In contrast, inhibiting SIRT1 by pretreatment with Ex527 abrogated the protective actions of CAG both in vivo and in vitro models of SAH. Collectively, our findings indicated that CAG could be a promising and effective drug candidate for SAH. Hindawi 2022-06-02 /pmc/articles/PMC9184193/ /pubmed/35693703 http://dx.doi.org/10.1155/2022/3099409 Text en Copyright © 2022 Weibin Lin 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
Lin, Weibin
Yao, Hao
Lai, Jinqing
Zeng, Yile
Guo, Xieli
Lin, Shu
Hu, Weipeng
Chen, Junyan
Chen, Xiangrong
Cycloastragenol Confers Cerebral Protection after Subarachnoid Hemorrhage by Suppressing Oxidative Insults and Neuroinflammation via the SIRT1 Signaling Pathway
title Cycloastragenol Confers Cerebral Protection after Subarachnoid Hemorrhage by Suppressing Oxidative Insults and Neuroinflammation via the SIRT1 Signaling Pathway
title_full Cycloastragenol Confers Cerebral Protection after Subarachnoid Hemorrhage by Suppressing Oxidative Insults and Neuroinflammation via the SIRT1 Signaling Pathway
title_fullStr Cycloastragenol Confers Cerebral Protection after Subarachnoid Hemorrhage by Suppressing Oxidative Insults and Neuroinflammation via the SIRT1 Signaling Pathway
title_full_unstemmed Cycloastragenol Confers Cerebral Protection after Subarachnoid Hemorrhage by Suppressing Oxidative Insults and Neuroinflammation via the SIRT1 Signaling Pathway
title_short Cycloastragenol Confers Cerebral Protection after Subarachnoid Hemorrhage by Suppressing Oxidative Insults and Neuroinflammation via the SIRT1 Signaling Pathway
title_sort cycloastragenol confers cerebral protection after subarachnoid hemorrhage by suppressing oxidative insults and neuroinflammation via the sirt1 signaling pathway
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9184193/
https://www.ncbi.nlm.nih.gov/pubmed/35693703
http://dx.doi.org/10.1155/2022/3099409
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