Open AccessImperatorin inhibits mitogen‐activated protein kinase and nuclear factor kappa‐B signaling pathways and alleviates neuroinflammation in ischemic stroke
Author(s) -
Ge Jianwei,
Deng Shiji,
Xue Zhiwei,
Liu Pinyi,
Yu Linjie,
Li Jiangnan,
Xia Shengnan,
Gu Yue,
Bao Xinyu,
Lan Zhen,
Xu Yun,
Zhu Xiaolei
Publication year - 2022
Publication title -
cns neuroscience and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 69
eISSN - 1755-5949
pISSN - 1755-5930
DOI - 10.1111/cns.13748
Subject(s) - neuroinflammation , imperatorin , microglia , western blot , mapk/erk pathway , pharmacology , medicine , signal transduction , proinflammatory cytokine , nf κb , inflammation , immunology , chemistry , biology , microbiology and biotechnology , biochemistry , high performance liquid chromatography , chromatography , gene
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.