Premium
Kellerin alleviates cognitive impairment in mice after ischemic stroke by multiple mechanisms
Author(s) -
Zhang Wenqiang,
Mi Yan,
Jiao Kun,
Xu Jikai,
Guo Tingting,
Zhou Di,
Zhang Xueni,
Ni Hui,
Sun Yu,
Wei Kun,
Li Ning,
Hou Yue
Publication year - 2020
Publication title -
phytotherapy research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.019
H-Index - 129
eISSN - 1099-1573
pISSN - 0951-418X
DOI - 10.1002/ptr.6676
Subject(s) - microglia , medicine , stroke (engine) , inflammation , ischemic stroke , neuroinflammation , brain ischemia , ischemia , pharmacology , immunology , neuroscience , biology , mechanical engineering , engineering
Ischemic stroke is a global disease with high disability and mortality rates. Cognitive impairment is one of the major clinical features of ischemic stroke, and microglia‐mediated inflammation has been shown to be an important contributor to the pathogenesis of ischemic stroke. Kellerin, extracted from Ferula sinkiangensis, was previously shown to inhibit microglial activation and exert a strong anti‐neuroinflammatory effect. However, there is no report of the potential therapeutic effect of kellerin on ischemic stroke by targeting microglial cells. In this study, we wanted to examine the effects of kellerin on ischemic stroke in the bilateral common carotid artery occlusion (BCCAO) model and the lipopolysaccharide (LPS)‐activated microglia model. We found that kellerin alleviated cognitive impairment, decreased neuronal loss, suppressed microglial activation, and transformed microglia from the pro‐inflammatory M1 phenotype to the anti‐inflammatory M2 phenotype in BCCAO mice. Moreover, in in vitro studies, we found that kellerin regulated microglial polarization and inhibited the NLRP3 and MAPK signaling pathways after LPS treatment. These findings provide a new understanding of the function of kellerin in ischemic stroke, and suggest that kellerin could be a potential therapeutic agent for the treatment of ischemic stroke.