Alismol, a Sesquiterpenoid Isolated from Vladimiria souliei, Suppresses Proinflammatory Mediators in Lipopolysaccharide-Stimulated Microglia.

Microglia activation plays an important role in the pathogenesis of various neurodegenerative diseases by producing neurotoxic factors, such as proinflammatory cytokines and nitric oxide (NO); therefore, suppression of microglia activation is a potential therapeutic approach against these diseases. Previous study showed that alismol, a sesquiterpenoid isolated from the roots of Vladimiria souliei inhibits interferon-γ-induced NO production in murine macrophage RAW264.7 cells. In the present study, we found that alismol reduced NO and prostaglandin E (PGE) levels and suppressed the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in lipopolysaccharide (LPS)-stimulated primary and cultured microglia. Alismol also inhibited the mRNA and protein expression of proinflammatory cytokines including interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α. Further mechanistic studies revealed that alismol inhibited LPS-induced nuclear factor-κB (NF-κB) activation but not mitogen-activated protein kinase (MAPK) pathway. Finally, we demonstrated the neuroprotective effects of alismol in microglia-neuron coculture systems. Collectively, these results suggest that the inhibition of microglia activation by alismol may provide potential therapeutic strategy for various neuroinflammatory diseases.