Isorhynchophylline ameliorates cerebral ischemia/reperfusion injury by inhibiting CX3CR1-mediated microglial activation and neuroinflammation

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

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

11 Citations (Scopus)
11 Downloads (Pure)

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 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.

Original languageEnglish
Article number574793
Pages (from-to)1-9
Number of pages9
JournalFrontiers in Pharmacology
Volume12
DOIs
Publication statusPublished - 12 Feb 2021
Externally publishedYes

Bibliographical note

Copyright the Author(s) 2021. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

Keywords

  • C-X3-C motif chemokine receptor 1
  • cerebral ischemia/reperfusion injury
  • Isorhynchophylline
  • microglia
  • neuroinflammation

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