Hyperforin protects against acute cerebral ischemic injury through inhibition of interleukin-17A-mediated microglial activation.

Abstract

Hyperforin, a pharmacologically active component of the medicinal plant Hypericum perforatum (St. John's wort), has been shown to be neuroprotective against acute ischemic stroke. However, the underlying mechanisms are still unclear and need to be fully elucidated. C57BL/6 wildtype (WT) mice or interleukin (IL)-17A knock-out mice were subjected to middle cerebral artery occlusion (60min) followed by reperfusion for 72h. Hyperforin (0.5μg) was injected slowly into the right ventricle of WT mice 1, 24 and 48h after middle cerebral artery occlusion (MCAO) onset. Here, we found that hyperforin treatment decreased the mRNA and protein expression of IL-17A at 72h after MCAO onset. Hyperforin reduced infarct volumes and increased neurologic scores accompanied by a decrease in microglial activation and a shift from M1 to M2 phenotypes in the peri-infarct striatum. Furthermore, we revealed that IL-17A was essential to the microglial activation in the acute phase of ischemic stroke. IL-17A knock-out (il-17a-/-) or anti-IL-17 A monoclonal antibody treatment markedly decreased the microglial activation and induced a shift from M1 to M2 phenotypes of activated microglia. In addition, treatment with recombinant mouse IL-17A abolished the protective effects of hyperforin on acute ischemic brain injury, attenuated the inhibitory effects of hyperforin on the microglial activation, and inhibited the enhanced shift from M1 to M2 phenotypes mediated by hyperforin. In conclusion, our results clearly showed that hyperforin could protect against acute cerebral ischemic injury through inhibition of interleukin-17A-mediated microglial activation and polarization of microglia to M2 phenotype.

• Authors: Li Ma, Xia Pan, Fang Zhou, Kang Liu, Long Wang
• Journal: Brain research (Brain Res) Vol. 1678 Pg. 254-261 (Jan 01 2018) ISSN: 1872-6240 [Electronic] Netherlands
• PMID: 28870826 (Publication Type: Journal Article)
• Copyright: Copyright © 2017. Published by Elsevier B.V.

Chemical References

• Cytokines
• Intercellular Signaling Peptides and Proteins
• Interleukin-17
• Neuroprotective Agents
• Terpenes
• Phloroglucinol
• hyperforin

Topics

• Animals
• Brain Infarction (etiology)
• Brain Injuries (drug therapy, etiology, pathology)
• Cytokines (genetics, metabolism)
• Disease Models, Animal
• Exploratory Behavior (drug effects)
• Gene Expression Regulation (drug effects, genetics)
• Infarction, Middle Cerebral Artery (complications)
• Intercellular Signaling Peptides and Proteins (genetics, metabolism)
• Interleukin-17 (genetics, metabolism)
• Male
• Mice
• Mice, Inbred C57BL
• Mice, Transgenic
• Microglia (drug effects, metabolism)
• Neuroprotective Agents (pharmacology, therapeutic use)
• Phloroglucinol (analogs & derivatives, pharmacology, therapeutic use)
• Proprioception (drug effects)
• Statistics, Nonparametric
• Terpenes (pharmacology, therapeutic use)