Anti-inflammatory effects of isoalantolactone on LPS-stimulated BV2 microglia cells through activating GSK-3β-Nrf2 signaling pathway

Abstract Isoalantolactone (ISO) is a sesquiterpene lactone isolated from Inula helenium that has been known to exhibit anti-inflammatory effect. Nevertheless, the effects of ISO on neuroinflammation have not been explored. BV2 microglia cells were pretreated with ISO and then stimulated with LPS. ISO attenuated the production of inflammatory mediators, such as TNF-α, IL-1β, NO, and PGE 2 in LPS-stimulated BV2 microglia cells. ISO suppressed the LPS-induced NF-κB activation in a concentration-dependent manner. The expression of Nrf2 and HO-1 were increased by the treatment of ISO. Inhibition of Nrf2 by siRNA could reverse the anti-inflammatory effects of ISO, as confirmed by the reversed inflammatory mediator production. Furthermore, ISO increased the level of phosphorylated GSK-3β, the upstream molecule of Nrf2. In conclusion, these results indicated that ISO might exhibit its anti-inflammatory effects through activating GSK-3β-Nrf2 signaling pathway.