Ischemic stroke is a devastating disease with high morbidity and mortality rates, and the proinflammatory microglia-mediated inflammatory response directly affects
stroke outcome. Previous studies have reported that
JLX001, a novel compound with a structure similar to that of
cyclovirobuxine D (
CVB-D), exerts antiapoptotic, anti-inflammatory and antioxidative effects on
ischemia-induced
brain injury. However, the role of
JLX001 in microglial polarization and
nucleotide-binding oligomerization domain (
NOD)-like receptor family pyrin domain-containing 3 (NLRP3)
inflammasome regulation after
ischemic stroke has not been fully investigated. In this study, we used the
middle cerebral artery occlusion (MCAO) method to establish a focal
cerebral ischemia model and found that
JLX001 attenuated the
brain infarct size and improved cerebral damage. Moreover, the expression levels of proinflammatory
cytokines (
interleukin [IL]-1β and
tumor necrosis factor [TNF]-α) were significantly reduced while those of the anti-inflammatory
cytokine IL-10 were increased in the JLX001-treated group. Immunofluorescence staining and flow cytometry revealed an increased number of anti-inflammatory phenotypic microglia and a reduced number of proinflammatory phenotypic microglia in JLX001-treated MCAO mice. Western blotting analysis showed that
JLX001 inhibited the expression of NLRP3 and
proteins related to the NLRP3
inflammasome axis in vivo. Furthermore,
JLX001 reduced the number of NLRP3/Iba1 cells in ischemic penumbra tissues. Finally, mechanistic analysis revealed that
JLX001 significantly inhibited the expression of
proteins related to the NF-κB signaling pathway. Additionally,
pyrrolidine dithiocarbamate (
PDTC), an NF-κB inhibitor, ameliorated
cerebral ischemia-
reperfusion injury by suppressing microglial polarization towards the proinflammatory phenotype and NLRP3 activation in vivo, further suggesting that these protective effects of
JLX001 were mediated by inhibition of the NF-κB signaling pathway. These results suggest that
JLX001 is a promising therapeutic approach for
ischemic stroke.