Scutellarin suppresses neuroinflammation via the inhibition of the AKT/NF-κB and p38/JNK pathway in LPS-induced BV-2 microglial cells.

Abstract

In vitro and in vivo studies indicate that scutellarin (SCU) exerts anti-inflammatory effects in the central nervous system (CNS) and inhibits microglia activation. This study investigated the anti-neuroinflammation molecular mechanisms exerted by scutellarin in LPS-induced BV-2 cells. The results showed that production of TNF-α, IL-1β, IL-6, and NO and TNF-α, IL-1β, IL-6, and iNOS mRNA were inhibited by scutellarin, which was independent of cytotoxicity as assessed by a CCK8 assay. Western blot analysis indicated that NF-κB-p65 phosphorylation was suppressed by scutellarin via inhibition of IκB degradation and IKKβ activation, which coincided with blockage of nuclear translocation of NF-κB as shown by immunofluorescent staining. Consistent with the inhibition of NF-κB, scutellarin inhibited the phosphorylation of p38, JNK, and AKT without affecting phosphorylation of ERK1/2 or PI3K in LPS-induced BV-2 cells. Overall, the present study suggests that scutellarin inhibits the production of pro-inflammatory mediators via inhibition of the IKK-dependent NF-κB and p38/JNK signaling pathway, which inhibits microglia activation and exerts anti-inflammation, indicating its potential therapeutic effect for neurodegenerative and cerebrovascular diseases.