Aims: Microglia-mediated neuroinflammation plays an important role in the pathological process of ischemic stroke, and the effect of imperatorin on post-stroke neuroinflammation is not fully understood.
Methods: Primary microglia were treated with imperatorin for 2 h followed by LPS (100 ng/ml) for 24 h. The expression of inflammatory cytokines was detected by RT-PCR, ELISA, and Western blot. The activation of MAPK and NF-κB signaling pathways were analyzed by Western blot. The ischemic insult was determined using a transient middle cerebral artery occlusion (tMCAO) model in C57BL/6J mice. Behavior tests were used to assess the neurological deficits of MCAO mice. TTC staining was applied to measure infract volume.
Results: Imperatorin suppressed LPS-induced activation of microglia and pro-inflammatory cytokines release and attenuated ischemic injury in MCAO mice. The results of transcriptome sequencing and Western blot revealed that downregulation of MAPK and NF-κB pathways might contribute to the protective effects of imperatorin.
Conclusions: Imperatorin downregulated MAPK and NF-κB signaling pathways and exerted anti-inflammatory effects in ischemic stroke, which indicated that imperatorin might be a potential compound for the treatment of stroke.
Keywords: MAPK pathway; NF-κB pathway; imperatorin; ischemic stroke; microglia; neuroinflammation.
© 2021 The Authors. CNS Neuroscience & Therapeutics Published by John Wiley & Sons Ltd.