Nrf2 activation by neferine mitigates microglial neuroinflammation after subarachnoid hemorrhage through inhibiting TAK1-NF-κB signaling
Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved..
Oxidative stress and neuroinflammation are two major causes leading to early brain injury after subarachnoid hemorrhage (SAH). Nuclear factor E2-related factor 2 (Nrf2) is a critical transcription factor that contributes to antioxidant responses. Additionally, Nrf2 could inhibit transforming growth factor beta-activated kinase 1 (TAK1), which plays a vital role in microglial activation-mediated neuroinflammation. Neferine (NE) exhibits considerable protective effects in diverse disease models. However, the detailed effect and mechanism of NE on SAH remain unknown. Our data showed that NE treatment significantly reduced behavior and cognitive impairment, and brain edema in the early period after SAH. In addition, NE mitigated SAH-induced oxidative damage, neuroinflammation, and neural death. Moreover, NE inhibited M1 microglial polarization and enhanced M2 phenotype microglia both in vivo and in vitro. Further investigations revealed that NE enhanced the Nrf2-antioxidant response element (ARE) signaling pathway and suppressed TAK1-NF-κB signaling. In contrast, depletion of Nrf2 by ML385 suppressed Nrf2-ARE signaling, induced TAK1-NF-κB activation, and further promoted M1 microglial polarization. Additionally, ML385 abated the neuroprotective effects of NE against SAH. Notably, LPS also aggravated TAK1-NF-κB activation and reversed the beneficial effects of NE after SAH. In summary, NE provides protection after SAH by inhibiting oxidative stress and modulating microglial polarization through Nrf2 activation and TAK1-NF-κB suppression.
Medienart: |
E-Artikel |
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Erscheinungsjahr: |
2024 |
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Erschienen: |
2024 |
Enthalten in: |
Zur Gesamtaufnahme - volume:130 |
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Enthalten in: |
International immunopharmacology - 130(2024) vom: 30. März, Seite 111693 |
Sprache: |
Englisch |
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Beteiligte Personen: |
Zhang, Xiaotian [VerfasserIn] |
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Links: |
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Themen: |
2292-16-2 |
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Anmerkungen: |
Date Completed 25.03.2024 Date Revised 27.03.2024 published: Print-Electronic Citation Status MEDLINE |
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doi: |
10.1016/j.intimp.2024.111693 |
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funding: |
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Förderinstitution / Projekttitel: |
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PPN (Katalog-ID): |
NLM369180224 |
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520 | |a Oxidative stress and neuroinflammation are two major causes leading to early brain injury after subarachnoid hemorrhage (SAH). Nuclear factor E2-related factor 2 (Nrf2) is a critical transcription factor that contributes to antioxidant responses. Additionally, Nrf2 could inhibit transforming growth factor beta-activated kinase 1 (TAK1), which plays a vital role in microglial activation-mediated neuroinflammation. Neferine (NE) exhibits considerable protective effects in diverse disease models. However, the detailed effect and mechanism of NE on SAH remain unknown. Our data showed that NE treatment significantly reduced behavior and cognitive impairment, and brain edema in the early period after SAH. In addition, NE mitigated SAH-induced oxidative damage, neuroinflammation, and neural death. Moreover, NE inhibited M1 microglial polarization and enhanced M2 phenotype microglia both in vivo and in vitro. Further investigations revealed that NE enhanced the Nrf2-antioxidant response element (ARE) signaling pathway and suppressed TAK1-NF-κB signaling. In contrast, depletion of Nrf2 by ML385 suppressed Nrf2-ARE signaling, induced TAK1-NF-κB activation, and further promoted M1 microglial polarization. Additionally, ML385 abated the neuroprotective effects of NE against SAH. Notably, LPS also aggravated TAK1-NF-κB activation and reversed the beneficial effects of NE after SAH. In summary, NE provides protection after SAH by inhibiting oxidative stress and modulating microglial polarization through Nrf2 activation and TAK1-NF-κB suppression | ||
650 | 4 | |a Journal Article | |
650 | 4 | |a Early brain injury | |
650 | 4 | |a Microglia | |
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700 | 1 | |a Cao, Changchun |e verfasserin |4 aut | |
700 | 1 | |a Liu, Zhichao |e verfasserin |4 aut | |
700 | 1 | |a Chen, Qiushi |e verfasserin |4 aut | |
700 | 1 | |a Gu, Zhijiang |e verfasserin |4 aut | |
700 | 1 | |a Wang, Weijie |e verfasserin |4 aut | |
700 | 1 | |a Fang, Dazhao |e verfasserin |4 aut | |
700 | 1 | |a Ge, QianQian |e verfasserin |4 aut | |
700 | 1 | |a Ding, Lianshu |e verfasserin |4 aut | |
700 | 1 | |a Pang, Cong |e verfasserin |4 aut | |
700 | 1 | |a Wang, Xiaodong |e verfasserin |4 aut | |
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