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

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 c...

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Main Authors: Yuanyuan Deng (Author), Ruirong Tan (Author), Fei Li (Author), Yuangui Liu (Author), Jingshan Shi (Author), Qihai Gong (Author)
Format: Book
Published: Frontiers Media S.A., 2021-02-01T00:00:00Z.
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042 |a dc 
100 1 0 |a Yuanyuan Deng  |e author 
700 1 0 |a Yuanyuan Deng  |e author 
700 1 0 |a Ruirong Tan  |e author 
700 1 0 |a Ruirong Tan  |e author 
700 1 0 |a Fei Li  |e author 
700 1 0 |a Fei Li  |e author 
700 1 0 |a Yuangui Liu  |e author 
700 1 0 |a Yuangui Liu  |e author 
700 1 0 |a Jingshan Shi  |e author 
700 1 0 |a Jingshan Shi  |e author 
700 1 0 |a Qihai Gong  |e author 
700 1 0 |a Qihai Gong  |e author 
245 0 0 |a Isorhynchophylline Ameliorates Cerebral Ischemia/Reperfusion Injury by Inhibiting CX3CR1-Mediated Microglial Activation and Neuroinflammation 
260 |b Frontiers Media S.A.,   |c 2021-02-01T00:00:00Z. 
500 |a 1663-9812 
500 |a 10.3389/fphar.2021.574793 
520 |a 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 Uncaria rhynchophylla, 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. 
546 |a EN 
690 |a Isorhynchophylline 
690 |a cerebral ischemia/reperfusion injury 
690 |a neuroinflammation 
690 |a microglia 
690 |a C-X3-C motif chemokine receptor 1 
690 |a Therapeutics. Pharmacology 
690 |a RM1-950 
655 7 |a article  |2 local 
786 0 |n Frontiers in Pharmacology, Vol 12 (2021) 
787 0 |n https://www.frontiersin.org/articles/10.3389/fphar.2021.574793/full 
787 0 |n https://doaj.org/toc/1663-9812 
856 4 1 |u https://doaj.org/article/2f2fda728c69423e9ab8fc43b81e0200  |z Connect to this object online.