Deoxyelephantopin from Elephantopus scaber modulates neuroinflammatory response through MAPKs and PI3K/Akt-dependent NF-κB signaling pathways in LPS-stimulated BV-2 microglial cells

Microglial activation which results in neuroinflammation, plays a great significance in the pathogenesis of neurodegenerative diseases by secreting various neurotoxic factors. Suppression of microglial activation by the natural-derived compounds may ameliorate neurodegenerative processes. The anti-inflammatory activity of deoxyelephantopin (DET) from the ethyl acetate fraction of Elephantopus scaber was studied against LPS-stimulated BV-2 cells. Deoxyelephantopin suppressed the production of nitric oxide and prostaglandin E-2 by inhibiting the LPS-induced inducible nitric oxide synthase and cyclooxygenase-2. DET inhibited nuclear translocation of nuclear factor-kappa B (NF-kappa B) and I kappa B alpha phosphorylation by suppressing phosphoiylation of PI3K/Akt and mitogen-activated protein kinases (MAPKs) pathways in BV-2 cells. Interestingly, the enhancement of anti-inflammatory cytokines, interleukin (IL)-4 and IL-10 concomitantly with the reduction of pro-inflammatory cytokines (Interferon-gamma, IL-1 beta, IL-2, IL-6, IL-12 and tumor necrosis factor-alpha), chemokines (CCL21 and CCL5/RANTES) and galectin-3 were found upon DET treatment. Taken together, present study further advocates DET as a potential novel anti-neuroinflammatory agent in the intervention of neurodegenerative diseases. (C) 2017 Elsevier Ltd. All rights reserved.