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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| Format: | Article |
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Frontiers Media S.A.
2021-07-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2021.710358/full |
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| author | Zhuqing Jin Zhuqing Jin Jian Liang Pappachan E. Kolattukudy |
| author_facet | Zhuqing Jin Zhuqing Jin Jian Liang Pappachan E. Kolattukudy |
| author_sort | Zhuqing Jin |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-20T02:22:04Z |
| format | Article |
| id | doaj.art-41219dd1c1a042579afeb3ac17368b12 |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-12-20T02:22:04Z |
| publishDate | 2021-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-41219dd1c1a042579afeb3ac17368b122022-12-21T19:56:48ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122021-07-011210.3389/fphar.2021.710358710358Tetramethylpyrazine Preserves the Integrity of Blood-Brain Barrier Associated With Upregulation of MCPIP1 in a Murine Model of Focal Ischemic StrokeZhuqing Jin0Zhuqing Jin1Jian Liang2Pappachan E. Kolattukudy3School of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, ChinaBurnett School of Biomedical Sciences, University of Central Florida College of Medicine, Orlando, FL, United StatesBurnett School of Biomedical Sciences, University of Central Florida College of Medicine, Orlando, FL, United StatesBurnett School of Biomedical Sciences, University of Central Florida College of Medicine, Orlando, FL, United StatesTetramethylpyrazine (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.https://www.frontiersin.org/articles/10.3389/fphar.2021.710358/fulltetramethylpyrazineMCPIP1middle cerebral artery occlusionreperfusionblood-brain barrier |
| spellingShingle | Zhuqing Jin Zhuqing Jin Jian Liang Pappachan E. Kolattukudy Tetramethylpyrazine Preserves the Integrity of Blood-Brain Barrier Associated With Upregulation of MCPIP1 in a Murine Model of Focal Ischemic Stroke Frontiers in Pharmacology tetramethylpyrazine MCPIP1 middle cerebral artery occlusion reperfusion blood-brain barrier |
| 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 | tetramethylpyrazine MCPIP1 middle cerebral artery occlusion reperfusion blood-brain barrier |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2021.710358/full |
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