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异钩藤碱通过抑制CX3CR1介导的小胶质细胞激活和神经炎症来改善脑缺血/再灌注损伤。

Isorhynchophylline Ameliorates Cerebral Ischemia/Reperfusion Injury by Inhibiting CX3CR1-Mediated Microglial Activation and Neuroinflammation.

作者信息

Deng Yuanyuan, Tan Ruirong, Li Fei, Liu Yuangui, Shi Jingshan, Gong Qihai

机构信息

Key Laboratory of Basic Pharmacology of Ministry of Education, Department of Pharmacology, Zunyi Medical University, Zunyi, China.

Joint International Research Laboratory of Ethnomedicine of Ministry of Education, Zunyi Medical University, Zunyi, China.

出版信息

Front Pharmacol. 2021 Feb 12;12:574793. doi: 10.3389/fphar.2021.574793. eCollection 2021.

DOI:10.3389/fphar.2021.574793
PMID:33643044
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7907603/
Abstract

Reperfusion therapy is an effective way to rescue cerebral ischemic injury, but this therapy also shows the detrimental risk of devastating disorders and death due to the possible inflammatory responses involved in the pathologies. Hence, the therapy of ischemia/reperfusion (I/R) injury is a great challenge currently. Isorhynchophylline (IRN), a tetracyclic oxindole alkaloid extracted from , has previously shown neuroprotective and anti-inflammatory effects in microglial cells. This study systematically investigates the effect of IRN on I/R injury and its underlying mechanism. The effects of IRN on neuronal injury and microglia-mediated inflammatory response were assessed on a rat model with middle cerebral artery occlusion (MCAO) and reperfusion-induced injury. We found that IRN treatment attenuated the infarct volume and improved the neurological function in I/R injury rats. IRN treatment also reduced the neuronal death rate, brain water content, and aquaporin-4 expression in the ischemic penumbra of I/R injury rats' brains. Besides, IRN treatment could inhibit the following process, including IκB-α degradation, NF-κB p65 activation, and CX3CR1 expression, as well as the microglial activation and inflammatory response. These findings suggest that IRN is a promising candidate to treat the cerebral I/R injury via inhibiting microglia activation and neuroinflammation.

摘要

再灌注疗法是挽救脑缺血损伤的有效方法，但由于该疗法可能涉及病理过程中的炎症反应，也存在引发严重紊乱和死亡的有害风险。因此，缺血/再灌注（I/R）损伤的治疗目前是一项巨大挑战。异钩藤碱（IRN）是从[具体植物]中提取的一种四环氧化吲哚生物碱，先前已在小胶质细胞中显示出神经保护和抗炎作用。本研究系统地探讨了IRN对I/R损伤的影响及其潜在机制。在大脑中动脉闭塞（MCAO）和再灌注诱导损伤的大鼠模型上评估了IRN对神经元损伤和小胶质细胞介导的炎症反应的影响。我们发现，IRN治疗可减轻I/R损伤大鼠的梗死体积并改善神经功能。IRN治疗还降低了I/R损伤大鼠脑缺血半暗带的神经元死亡率、脑含水量和水通道蛋白-4表达。此外，IRN治疗可抑制以下过程，包括IκB-α降解、NF-κB p65激活和CX3CR1表达，以及小胶质细胞激活和炎症反应。这些发现表明，IRN有望通过抑制小胶质细胞激活和神经炎症来治疗脑I/R损伤。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a729/7907603/9e9d6316d380/fphar-12-574793-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a729/7907603/18797121031b/fphar-12-574793-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a729/7907603/044752090542/fphar-12-574793-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a729/7907603/fbe36de58f36/fphar-12-574793-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a729/7907603/bad7aa0e97ec/fphar-12-574793-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a729/7907603/8229ffce10e6/fphar-12-574793-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a729/7907603/9e9d6316d380/fphar-12-574793-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a729/7907603/18797121031b/fphar-12-574793-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a729/7907603/044752090542/fphar-12-574793-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a729/7907603/fbe36de58f36/fphar-12-574793-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a729/7907603/bad7aa0e97ec/fphar-12-574793-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a729/7907603/8229ffce10e6/fphar-12-574793-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a729/7907603/9e9d6316d380/fphar-12-574793-g006.jpg

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本文引用的文献

[1]
Isorhynchophylline ameliorates cognitive impairment via modulating amyloid pathology, tau hyperphosphorylation and neuroinflammation: Studies in a transgenic mouse model of Alzheimer's disease.

Brain Behav Immun. 2019-8-30

[2]
Isorhynchophylline exerts antidepressant-like effects in mice modulating neuroinflammation and neurotrophins: involvement of the PI3K/Akt/GSK-3β signaling pathway.

FASEB J. 2019-6-24

[3]
Isorhynchophylline exerts anti-inflammatory and anti-oxidative activities in LPS-stimulated murine alveolar macrophages.

Life Sci. 2019-3-8

[4]
Evidence on Integrating Pharmacokinetics to Find Truly Therapeutic Agent for Alzheimer's Disease: Comparative Pharmacokinetics and Disposition Kinetics Profiles of Stereoisomers Isorhynchophylline and Rhynchophylline in Rats.

Evid Based Complement Alternat Med. 2019-2-3

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Front Pharmacol. 2018-10-23

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The Blood-Brain Barrier Permeability of Six Indole Alkaloids from Uncariae Ramulus Cum Uncis in the MDCK-pHaMDR Cell Monolayer Model.

Molecules. 2017-11-10

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Icariside II, a Broad-Spectrum Anti-cancer Agent, Reverses Beta-Amyloid-Induced Cognitive Impairment through Reducing Inflammation and Apoptosis in Rats.

Front Pharmacol. 2017-2-2

[9]
Icariside II protects against cerebral ischemia-reperfusion injury in rats via nuclear factor-κB inhibition and peroxisome proliferator-activated receptor up-regulation.

Neurochem Int. 2016-6

[10]
Icariin, a major constituent of flavonoids from Epimedium brevicornum, protects against cognitive deficits induced by chronic brain hypoperfusion via its anti-amyloidogenic effect in rats.

Pharmacol Biochem Behav. 2015-11

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