Micheliolide suppresses LPS-induced neuroinflammatory responses.

Abstract

Microglia-involved neuroinflammation is thought to promote brain damage in various neurodegenerative disorders. Thus, inhibition of microglial over-activation may have a therapeutic benefit for the treatment of neurodegenerative disorders. Micheliolide (MCL) is a sesquiterpene lactone which inhibits various inflammatory response. However, whether MCL can inhibit neuroinflammation caused by LPS-activated BV2 microglia has not yet been explored. In this study, we demonstrated that treatment of BV2 cells with MCL significantly repressed LPS-stimulated nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression, as well as tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and nitric oxide (NO) induction. MCL also attenuated mRNA levels of multiple pro-inflammatory cytokines and mediators such as iNOS, COX-2, TNF-α, IL-6 and IL-1β. Mechanistic studies revealed that MCL suppressed LPS-stimulated the activation of IκBα/NF-κB pathway and Akt pathway. Moreover, MCL inhibited LPS-induced the activition of c-Jun N-terminal kinase (JNK), p38 MAPK kinase, and extracellular signal-regulated kinases 1/2 (ERK1/2). Meanwhile, MCL markedly promoted antioxidant protein heme oxygenase-1 (HO-1) expression by enhancing NF-E2-related factor 2 (Nrf2) activity. Together, our results imply that MCL may serve as a neuroprotective agent in neuroinflammation-related neurodegenerative disorders.