Kellerin alleviates cognitive impairment in mice after ischemic stroke by multiple mechanisms

Abstract

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.

Ferula sinkiangensis (Chou-AWei, Chinese Ferula): Traditional Uses, Phytoconstituents, Biosynthesis, and Pharmacological Activities

“…Moreover, it organized microglial polarization and suppressed the MAPK (mitogen-activated protein kinase) and NLRP3 signaling pathways subsequent to LPS-treatment in vitro. These findings highlighted the possible activity of 12 for treating ischemic stroke [ 49 ].…”

Okanin from Coreopsis tinctoria Nutt. alleviates cognitive impairment in bilateral common carotid artery occlusion mice by regulating the miR-7/NLRP3 axis in microglia

“…[22][23][24][25][26] The BCCAO surgery was performed as previously reported. 27 Briefly, common carotid arteries were exposed and separated carefully and then clamped for 30 min with aneurysm clips. The mice in the BCCAO group and the BCCAO + Okanin group underwent the BCCAO surgery.…”

Neurological disorders of COVID-19: insights to applications of natural products from plants and microorganisms

“…Kellerin exhibited an inspiring therapeutic potency for ischemic stroke through the alleviation of the cognitive impairment of bilateral common carotid artery occlusion mice by transforming microglia from pro-inflammatory M1 phenotype to anti-inflammatory M2. Furthermore, LPS-induced microglial polarization could be regulated by kellerin by inhibiting NLRP3 and MAPK signaling pathways (Zhang et al 2020a ).…”