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SIRT1 activation by 2,3,5,6-tetramethylpyrazine alleviates neuroinflammation via inhibiting M1 microglia polarization

BACKGROUND: Neuroinflammation has been reported as a potential contributing factor to brain diseases, and is characterized by activated microglia with release of multiple inflammatory mediators. 2,3,5,6-Tetramethylpyrazine (TMP) is an active alkaloid in Ligusticum chuanxiong Hort. and has various bi...

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Autores principales: Chen, Yu, Peng, Fu, Yang, Chao, Hou, Huan, Xing, Ziwei, Chen, Junren, Liu, Li, Peng, Cheng, Li, Dan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10436537/
https://www.ncbi.nlm.nih.gov/pubmed/37600790
http://dx.doi.org/10.3389/fimmu.2023.1206513
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author Chen, Yu
Peng, Fu
Yang, Chao
Hou, Huan
Xing, Ziwei
Chen, Junren
Liu, Li
Peng, Cheng
Li, Dan
author_facet Chen, Yu
Peng, Fu
Yang, Chao
Hou, Huan
Xing, Ziwei
Chen, Junren
Liu, Li
Peng, Cheng
Li, Dan
author_sort Chen, Yu
collection PubMed
description BACKGROUND: Neuroinflammation has been reported as a potential contributing factor to brain diseases, and is characterized by activated microglia with release of multiple inflammatory mediators. 2,3,5,6-Tetramethylpyrazine (TMP) is an active alkaloid in Ligusticum chuanxiong Hort. and has various biological activities, including anti-inflammatory and neuroprotection properties. However, the anti-neuroinflammatory activity of TMP has been less studied and its potential molecular mechanisms in this field remain unclear. This study aimed to investigate the effects of TMP and its underlying mechanisms in neuroinflammation. METHODS: In vitro, lipopolysaccharide (LPS)-stimulated BV2 microglia were used to assess the effects of TMP on inflammatory cytokines as well as the components of the SIRT1/NF-κB signaling pathway, which were measured by using ELISA, western blotting, qRT-qPCR and immunofluorescence. Moreover, LPS-induced acute neuroinflammation model in mice was performed to detect whether TMP could exert anti-neuroinflammatory effects in vivo, and the EX527, a SIRT1 inhibitor, were given intraperitoneally every two days prior to TMP treatment. Serums and spinal trigeminal nucleus (Sp5) tissues were collected for ELISA assay, and the Sp5 tissues were used for HE staining, Nissl staining, immunofluorescence, qRT-PCR and western blotting. RESULTS: In vitro, TMP treatment significantly reduced the secretion of pro-inflammatory cytokines, including TNF-α and IL-6, promoted SIRT1 protein expression and inactivated NF-κB signaling pathway in LPS-induced neuroinflammation. Interestingly, pretreatment with EX527 blocked the therapeutic effects of TMP on neuroinflammation in vitro. Furthermore, TMP reduced the levels of pro-inflammatory cytokines and chemokines, and prevented microglia from polarizing towards a pro-inflammatory state through activating SIRT1 and inhibiting NF-κB activation in LPS-induced neuroinflammation in mice. And EX527 reversed the beneficial effects of TMP against LPS exposure in mice. CONCLUSION: In summary, this study unravels that TMP could mitigate LPS-induced neuroinflammation via SIRT1/NF-κB signaling pathway.
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spelling pubmed-104365372023-08-19 SIRT1 activation by 2,3,5,6-tetramethylpyrazine alleviates neuroinflammation via inhibiting M1 microglia polarization Chen, Yu Peng, Fu Yang, Chao Hou, Huan Xing, Ziwei Chen, Junren Liu, Li Peng, Cheng Li, Dan Front Immunol Immunology BACKGROUND: Neuroinflammation has been reported as a potential contributing factor to brain diseases, and is characterized by activated microglia with release of multiple inflammatory mediators. 2,3,5,6-Tetramethylpyrazine (TMP) is an active alkaloid in Ligusticum chuanxiong Hort. and has various biological activities, including anti-inflammatory and neuroprotection properties. However, the anti-neuroinflammatory activity of TMP has been less studied and its potential molecular mechanisms in this field remain unclear. This study aimed to investigate the effects of TMP and its underlying mechanisms in neuroinflammation. METHODS: In vitro, lipopolysaccharide (LPS)-stimulated BV2 microglia were used to assess the effects of TMP on inflammatory cytokines as well as the components of the SIRT1/NF-κB signaling pathway, which were measured by using ELISA, western blotting, qRT-qPCR and immunofluorescence. Moreover, LPS-induced acute neuroinflammation model in mice was performed to detect whether TMP could exert anti-neuroinflammatory effects in vivo, and the EX527, a SIRT1 inhibitor, were given intraperitoneally every two days prior to TMP treatment. Serums and spinal trigeminal nucleus (Sp5) tissues were collected for ELISA assay, and the Sp5 tissues were used for HE staining, Nissl staining, immunofluorescence, qRT-PCR and western blotting. RESULTS: In vitro, TMP treatment significantly reduced the secretion of pro-inflammatory cytokines, including TNF-α and IL-6, promoted SIRT1 protein expression and inactivated NF-κB signaling pathway in LPS-induced neuroinflammation. Interestingly, pretreatment with EX527 blocked the therapeutic effects of TMP on neuroinflammation in vitro. Furthermore, TMP reduced the levels of pro-inflammatory cytokines and chemokines, and prevented microglia from polarizing towards a pro-inflammatory state through activating SIRT1 and inhibiting NF-κB activation in LPS-induced neuroinflammation in mice. And EX527 reversed the beneficial effects of TMP against LPS exposure in mice. CONCLUSION: In summary, this study unravels that TMP could mitigate LPS-induced neuroinflammation via SIRT1/NF-κB signaling pathway. Frontiers Media S.A. 2023-08-04 /pmc/articles/PMC10436537/ /pubmed/37600790 http://dx.doi.org/10.3389/fimmu.2023.1206513 Text en Copyright © 2023 Chen, Peng, Yang, Hou, Xing, Chen, Liu, Peng and Li 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 Immunology
Chen, Yu
Peng, Fu
Yang, Chao
Hou, Huan
Xing, Ziwei
Chen, Junren
Liu, Li
Peng, Cheng
Li, Dan
SIRT1 activation by 2,3,5,6-tetramethylpyrazine alleviates neuroinflammation via inhibiting M1 microglia polarization
title SIRT1 activation by 2,3,5,6-tetramethylpyrazine alleviates neuroinflammation via inhibiting M1 microglia polarization
title_full SIRT1 activation by 2,3,5,6-tetramethylpyrazine alleviates neuroinflammation via inhibiting M1 microglia polarization
title_fullStr SIRT1 activation by 2,3,5,6-tetramethylpyrazine alleviates neuroinflammation via inhibiting M1 microglia polarization
title_full_unstemmed SIRT1 activation by 2,3,5,6-tetramethylpyrazine alleviates neuroinflammation via inhibiting M1 microglia polarization
title_short SIRT1 activation by 2,3,5,6-tetramethylpyrazine alleviates neuroinflammation via inhibiting M1 microglia polarization
title_sort sirt1 activation by 2,3,5,6-tetramethylpyrazine alleviates neuroinflammation via inhibiting m1 microglia polarization
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10436537/
https://www.ncbi.nlm.nih.gov/pubmed/37600790
http://dx.doi.org/10.3389/fimmu.2023.1206513
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