Taxifolin attenuates neuroinflammation and microglial pyroptosis via the PI3K/Akt signaling pathway after spinal cord injury.

International immunopharmacology(2023)

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摘要
Spinal cord injury (SCI) is a severe injury characterized by neuroinflammation and oxidative stress. Taxifolin is exhibits anti-inflammatory and antioxidative activities in neurologic diseases. However, the roles and mechanisms of taxifolin in neuroinflammation and microglial pyroptosis after SCI remain unclear. The present study aims to investigate the effect of taxifolin on SCI and its potential underlying mechanisms in in vivo and in vitro models. In this study, taxifolin markedly reduced microglial activation mediated oxidative stress, and inhibited the expression of pyroptosis-related proteins (NLRP3, GSDMD, ASC, and Caspase-1) and inflammatory cytokines (IL-1β and IL-18) after SCI, as shown by immunofluorescence staining and western blot assays. In addition, taxifolin promoted axonal regeneration and improved functional recovery after SCI. In vitro studies showed that taxifolin attenuated the activation of microglia and oxidative stress after lipopolysaccharide (LPS) + adenosine-triphosphate (ATP) stimulation in BV2 cells. We also observed that taxifolin inhibited the pyroptosis-related proteins and reduced the release of inflammatory cytokines. Moreover, to explore how taxifolin exerts its effects on microglial pyroptosis and axonal regeneration of neurons, we performed an in vitro study in BV-2 cells and PC12 cells co-culture. The results revealed that taxifolin facilitated axonal regeneration of PC12 cells in co-culture with LPS + ATP-induced BV-2 cells. Mechanistically, taxifolin regulated microglial pyroptosis via the PI3K/AKT signaling pathway. Taken together, these results suggest that taxifolin alleviates neuroinflammation and microglial pyroptosis through the PI3K/AKT signaling pathway after SCI, and promotes axonal regeneration and improves functional recovery, suggesting that taxifolin may represent a potential therapeutic agent for SCI.
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关键词
Axonal regeneration,Microglial pyroptosis,Neuroinflammation,Spinal cord injury,Taxifolin
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