Chronically activated microglia and brain vascular damage are major causes of neuroinflammation. The aim of this study was to determine the anti-inflammatory effects of nitro capsaicin, a newly modified capsaicin with less irritating characteristics, against microglial activation and brain microvascular endothelial cell damage. Using the SIMA9 microglia cell line, we found that nitro capsaicin reduced nitric oxide (NO) production in LPS-activated microglia better than its parent compound, capsaicin. Nitro capsaicin also decreased the expression of proinflammatory cytokines (TNF-α, IL-1β, and IL-6) and enhanced the levels of anti-inflammatory factors, IL-4 and IL-10, both at the mRNA and protein levels. In the TNF-α-induced vascular damage model, nitro capsaicin decreased expression and secretion of the proinflammatory cytokines IL-1β and IL-6. Phosphorylated NF-κB p65, a key transcription factor that stimulates the signaling of inflammatory pathways, was also reduced in the presence of nitro capsaicin, suggesting that the anti-inflammatory effects of nitro capsaicin were created through reducing NF-κB activation. Together, we concluded that nitro capsaicin has the potential to be further developed as an anti-neuroinflammatory agent.
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