Imperatorin inhibits mitogen-activated protein kinase and nuclear factor kappa-B signaling pathways and alleviates neuroinflammation in ischemic stroke

Area of Science:

• Neuroscience
• Pharmacology
• Immunology

Background:

• Neuroinflammation driven by microglia is critical in ischemic stroke pathology.
• The therapeutic potential of imperatorin in mitigating post-stroke neuroinflammation remains largely unexplored.

Purpose of the Study:

• To investigate the effects of imperatorin on microglia activation and neuroinflammation in an ischemic stroke model.
• To elucidate the underlying molecular mechanisms, specifically focusing on MAPK and NF-κB signaling pathways.

Main Methods:

• Primary microglia were stimulated with lipopolysaccharide (LPS) and treated with imperatorin.
• Inflammatory cytokine expression was quantified using RT-PCR, ELISA, and Western blot.
• A transient middle cerebral artery occlusion (tMCAO) mouse model was used to assess in vivo effects, including behavioral tests and infarct volume measurement.

Main Results:

• Imperatorin significantly suppressed LPS-induced microglial activation and the release of pro-inflammatory cytokines.
• In vivo, imperatorin treatment attenuated ischemic injury in MCAO mice, improving neurological deficits.
• Transcriptome sequencing and Western blot analysis indicated that imperatorin exerts its protective effects by downregulating the MAPK and NF-κB signaling pathways.

Conclusions:

• Imperatorin demonstrates significant anti-inflammatory effects in the context of ischemic stroke.
• The compound downregulates MAPK and NF-κB signaling pathways, contributing to its neuroprotective properties.
• Imperatorin represents a promising therapeutic candidate for the treatment of ischemic stroke.