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Tetramethylpyrazine Preserves the Integrity of Blood-Brain Barrier Associated With Upregulation of MCPIP1 in a Murine Model of Focal Ischemic Stroke

Tetramethylpyrazine (TMP), a prominent ingredient of Chinese herb Ligusticum chuanxiong Hort, is known to suppress neuroinflammation and protect blood-brain barrier (BBB) integrity. We investigated whether monocyte chemotactic protein-induced protein 1 (MCPIP1, also known as Regnase-1), a newly iden...

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Autores principales: Jin, Zhuqing, Liang, Jian, Kolattukudy, Pappachan E.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8355423/
https://www.ncbi.nlm.nih.gov/pubmed/34393790
http://dx.doi.org/10.3389/fphar.2021.710358
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author Jin, Zhuqing
Liang, Jian
Kolattukudy, Pappachan E.
author_facet Jin, Zhuqing
Liang, Jian
Kolattukudy, Pappachan E.
author_sort Jin, Zhuqing
collection PubMed
description Tetramethylpyrazine (TMP), a prominent ingredient of Chinese herb Ligusticum chuanxiong Hort, is known to suppress neuroinflammation and protect blood-brain barrier (BBB) integrity. We investigated whether monocyte chemotactic protein-induced protein 1 (MCPIP1, also known as Regnase-1), a newly identified zinc-finger protein, plays a role in TMP-mediated anti-inflammation and neuroprotection. Male C57BL/6 mice were subjected to focal cerebral ischemia induced by middle cerebral artery occlusion (MCAO) for 2 h, followed by reperfusion for 24 h. TMP (25 mg/kg or 50 mg/kg) or vehicle was administered intraperitoneally 12 h before and post MCAO. The TMP significantly upregulated MCPIP1 in the ischemic brain tissues and effectively inhibited extravasation of fluorescein isothiocyanate (FITC)-dextran, resulting in attenuation of brain edema. These effects of the TMP were associated with a significant reduction in levels of inflammatory cytokines tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, and MMP-9 in the ischemic brain tissues. The TMP upregulated the expression of MCPIP1 in primary cultures of neurons and protected against oxygen–glucose deprivation-induced neuron death, while this neuroprotective effect of TMP was abolished by knockdown of MCPIP1 using MCPIP1-specific siRNA. These results suggest that preservation of BBB integrity by TMP is associated with its anti-inflammatory activity. The effect of TMP is mediated, at least in part, via upregulation of MCPIP1 in the ischemic brain.
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spelling pubmed-83554232021-08-12 Tetramethylpyrazine Preserves the Integrity of Blood-Brain Barrier Associated With Upregulation of MCPIP1 in a Murine Model of Focal Ischemic Stroke Jin, Zhuqing Liang, Jian Kolattukudy, Pappachan E. Front Pharmacol Pharmacology Tetramethylpyrazine (TMP), a prominent ingredient of Chinese herb Ligusticum chuanxiong Hort, is known to suppress neuroinflammation and protect blood-brain barrier (BBB) integrity. We investigated whether monocyte chemotactic protein-induced protein 1 (MCPIP1, also known as Regnase-1), a newly identified zinc-finger protein, plays a role in TMP-mediated anti-inflammation and neuroprotection. Male C57BL/6 mice were subjected to focal cerebral ischemia induced by middle cerebral artery occlusion (MCAO) for 2 h, followed by reperfusion for 24 h. TMP (25 mg/kg or 50 mg/kg) or vehicle was administered intraperitoneally 12 h before and post MCAO. The TMP significantly upregulated MCPIP1 in the ischemic brain tissues and effectively inhibited extravasation of fluorescein isothiocyanate (FITC)-dextran, resulting in attenuation of brain edema. These effects of the TMP were associated with a significant reduction in levels of inflammatory cytokines tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, and MMP-9 in the ischemic brain tissues. The TMP upregulated the expression of MCPIP1 in primary cultures of neurons and protected against oxygen–glucose deprivation-induced neuron death, while this neuroprotective effect of TMP was abolished by knockdown of MCPIP1 using MCPIP1-specific siRNA. These results suggest that preservation of BBB integrity by TMP is associated with its anti-inflammatory activity. The effect of TMP is mediated, at least in part, via upregulation of MCPIP1 in the ischemic brain. Frontiers Media S.A. 2021-07-28 /pmc/articles/PMC8355423/ /pubmed/34393790 http://dx.doi.org/10.3389/fphar.2021.710358 Text en Copyright © 2021 Jin, Liang and Kolattukudy. 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
Jin, Zhuqing
Liang, Jian
Kolattukudy, Pappachan E.
Tetramethylpyrazine Preserves the Integrity of Blood-Brain Barrier Associated With Upregulation of MCPIP1 in a Murine Model of Focal Ischemic Stroke
title Tetramethylpyrazine Preserves the Integrity of Blood-Brain Barrier Associated With Upregulation of MCPIP1 in a Murine Model of Focal Ischemic Stroke
title_full Tetramethylpyrazine Preserves the Integrity of Blood-Brain Barrier Associated With Upregulation of MCPIP1 in a Murine Model of Focal Ischemic Stroke
title_fullStr Tetramethylpyrazine Preserves the Integrity of Blood-Brain Barrier Associated With Upregulation of MCPIP1 in a Murine Model of Focal Ischemic Stroke
title_full_unstemmed Tetramethylpyrazine Preserves the Integrity of Blood-Brain Barrier Associated With Upregulation of MCPIP1 in a Murine Model of Focal Ischemic Stroke
title_short Tetramethylpyrazine Preserves the Integrity of Blood-Brain Barrier Associated With Upregulation of MCPIP1 in a Murine Model of Focal Ischemic Stroke
title_sort tetramethylpyrazine preserves the integrity of blood-brain barrier associated with upregulation of mcpip1 in a murine model of focal ischemic stroke
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8355423/
https://www.ncbi.nlm.nih.gov/pubmed/34393790
http://dx.doi.org/10.3389/fphar.2021.710358
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