Protocatechuic acid attenuates cerebral aneurysm formation and progression by inhibiting TNF-alpha/Nrf-2/NF-kB-mediated inflammatory mechanisms in experimental rats

Our current research aims to examine whether protocatechuic acid (PCA) can be used as a therapeutic agent for the development of cerebral aneurysm (CA) and to elucidate the mechanisms behind this. We assessed the effects of PCA at 50 and 100 mg/kg on the activation of signaling pathways for tissue n...

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Autores principales:	Xiao Gang, Zhang Mei, Peng Xing, Jiang Guangyuan
Formato:	article
Lenguaje:	EN
Publicado:	De Gruyter 2021
Materias:	cerebral aneurysm protocatechuic acid macrophages inflammatory response mechanisms chemokines tnf-α signaling, nrf-2 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/cdc09b0653d341f8ab71452dff8101db
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spelling	oai:doaj.org-article:cdc09b0653d341f8ab71452dff8101db2021-12-05T14:10:40ZProtocatechuic acid attenuates cerebral aneurysm formation and progression by inhibiting TNF-alpha/Nrf-2/NF-kB-mediated inflammatory mechanisms in experimental rats2391-541210.1515/biol-2021-0012https://doaj.org/article/cdc09b0653d341f8ab71452dff8101db2021-02-01T00:00:00Zhttps://doi.org/10.1515/biol-2021-0012https://doaj.org/toc/2391-5412Our current research aims to examine whether protocatechuic acid (PCA) can be used as a therapeutic agent for the development of cerebral aneurysm (CA) and to elucidate the mechanisms behind this. We assessed the effects of PCA at 50 and 100 mg/kg on the activation of signaling pathways for tissue necrosis factor (TNF)-α/nuclear factor (NF)-κB/nuclear factor erythroid 2 (Nrf-2) on progression and development in an elastase-induced CA model, accompanied by a high-salt diet to induce hypertension. The expression of inflammatory cytokines, chemokines, tumor necrosis factor-α, interleukins (IL)-8, IL-17, IL-6, IL-1β, and matrix metalloproteinase (MMP)-2 and MMP-9 was analyzed by ELISA, western blot, and reverse transcriptase quantative polymerase chain reaction. The expression levels of antioxidant enzymes and translocation of Nrf-2 were also determined. The group treated with PCA demonstrated a significant (P < 0.05) decrease in the aneurysmal size in rats compared to the CA-induced group. We found that PCA treatment suppressed the invasion of macrophage and activation of TNF-α/NF-κB/Nrf-2 signaling pathways. There was a significant decrease (P < 0.05) in pro-inflammatory cytokine and chemokine levels in a dose-dependent manner. We found that PCA treatment exerts protective effects by suppressing the development and progression of CA through the inhibition of inflammatory responses in macrophages via TNF-α/NF-κB/Nrf-2 signaling pathways, thus demonstrating that PCA can act as a treatment for CA.Xiao GangZhang MeiPeng XingJiang GuangyuanDe Gruyterarticlecerebral aneurysmprotocatechuic acidmacrophagesinflammatory response mechanismschemokinestnf-α signaling, nrf-2Biology (General)QH301-705.5ENOpen Life Sciences, Vol 16, Iss 1, Pp 128-141 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	cerebral aneurysm protocatechuic acid macrophages inflammatory response mechanisms chemokines tnf-α signaling, nrf-2 Biology (General) QH301-705.5
spellingShingle	cerebral aneurysm protocatechuic acid macrophages inflammatory response mechanisms chemokines tnf-α signaling, nrf-2 Biology (General) QH301-705.5 Xiao Gang Zhang Mei Peng Xing Jiang Guangyuan Protocatechuic acid attenuates cerebral aneurysm formation and progression by inhibiting TNF-alpha/Nrf-2/NF-kB-mediated inflammatory mechanisms in experimental rats
description	Our current research aims to examine whether protocatechuic acid (PCA) can be used as a therapeutic agent for the development of cerebral aneurysm (CA) and to elucidate the mechanisms behind this. We assessed the effects of PCA at 50 and 100 mg/kg on the activation of signaling pathways for tissue necrosis factor (TNF)-α/nuclear factor (NF)-κB/nuclear factor erythroid 2 (Nrf-2) on progression and development in an elastase-induced CA model, accompanied by a high-salt diet to induce hypertension. The expression of inflammatory cytokines, chemokines, tumor necrosis factor-α, interleukins (IL)-8, IL-17, IL-6, IL-1β, and matrix metalloproteinase (MMP)-2 and MMP-9 was analyzed by ELISA, western blot, and reverse transcriptase quantative polymerase chain reaction. The expression levels of antioxidant enzymes and translocation of Nrf-2 were also determined. The group treated with PCA demonstrated a significant (P < 0.05) decrease in the aneurysmal size in rats compared to the CA-induced group. We found that PCA treatment suppressed the invasion of macrophage and activation of TNF-α/NF-κB/Nrf-2 signaling pathways. There was a significant decrease (P < 0.05) in pro-inflammatory cytokine and chemokine levels in a dose-dependent manner. We found that PCA treatment exerts protective effects by suppressing the development and progression of CA through the inhibition of inflammatory responses in macrophages via TNF-α/NF-κB/Nrf-2 signaling pathways, thus demonstrating that PCA can act as a treatment for CA.
format	article
author	Xiao Gang Zhang Mei Peng Xing Jiang Guangyuan
author_facet	Xiao Gang Zhang Mei Peng Xing Jiang Guangyuan
author_sort	Xiao Gang
title	Protocatechuic acid attenuates cerebral aneurysm formation and progression by inhibiting TNF-alpha/Nrf-2/NF-kB-mediated inflammatory mechanisms in experimental rats
title_short	Protocatechuic acid attenuates cerebral aneurysm formation and progression by inhibiting TNF-alpha/Nrf-2/NF-kB-mediated inflammatory mechanisms in experimental rats
title_full	Protocatechuic acid attenuates cerebral aneurysm formation and progression by inhibiting TNF-alpha/Nrf-2/NF-kB-mediated inflammatory mechanisms in experimental rats
title_fullStr	Protocatechuic acid attenuates cerebral aneurysm formation and progression by inhibiting TNF-alpha/Nrf-2/NF-kB-mediated inflammatory mechanisms in experimental rats
title_full_unstemmed	Protocatechuic acid attenuates cerebral aneurysm formation and progression by inhibiting TNF-alpha/Nrf-2/NF-kB-mediated inflammatory mechanisms in experimental rats
title_sort	protocatechuic acid attenuates cerebral aneurysm formation and progression by inhibiting tnf-alpha/nrf-2/nf-kb-mediated inflammatory mechanisms in experimental rats
publisher	De Gruyter
publishDate	2021
url	https://doaj.org/article/cdc09b0653d341f8ab71452dff8101db
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Protocatechuic acid attenuates cerebral aneurysm formation and progression by inhibiting TNF-alpha/Nrf-2/NF-kB-mediated inflammatory mechanisms in experimental rats

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