Andalucin from Artemisia lannta suppresses the neuroinflammation via the promotion of Nrf2-mediated HO-1 levels by blocking the p65–p300 interaction in LPS-activated BV2 microglia

Abstract

BackgroundNeuroinflammation plays an important role in many neurodegenerative conditions such as Alzheimer's disease (AD) and Parkinson disease (PD). Andalucin (ADL), a sesquiterpene lactone from Artemisia lannta, has been reported to exhibit NO inhibition in vitro. However, the effect of ADL on microglia-mediated neuroinflammation has not been investigated. PurposeThis study was designed to determine the anti-neuroinflammatory effect of ADL against LPS-activated BV2 microglial cells and to explore the underlying mechanisms. MethodsThe production of pro-inflammatory mediators and cytokines were measured by ELISA. The relevant mechanisms were analyzed by qRT-PCR, Luciferase assay, Western blot and Co-immunoprecipitation Assay. ResultsADL inhibited the LPS-induced release of NO, PGE2, TNF-α, IL-6 and IL-1β. In addition, ADL reduced the mRNA and protein levels of iNOS and COX-2. Mechanism studies found that ADL activated Nrf2/HO-1 signaling pathway and suppressed NF-κB signaling pathway. Further investigation showed that the stimulative effect of ADL on Nrf2 transcriptional activity and the inhibitory effect of ADL on RelA transcriptional activity were due to its regulation on p300-Nrf2/p65 interaction. ConclusionADL displayed anti-neuroinflammatory activity in LPS-activated BV2 cells. The mechanism concerns its regulatory effect on the crosstalk between Nrf2 and p65.