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AIM Pseudoginsenoside-F11 (PF11), an ocotillol-type saponin, is one of the ingredients of Panax quinquefolium (American ginseng), previously isolated from leaves of Panax pseudoginseng subsp.himalaicus HARA (Himalayan Panax), but not in Panax ginseng.Our previous experiments showed that PF11 could improve the scopolamine-induced memory impairments in mice.In the present study, we assessed the anti-inflammatory effect of PF11 on the production of pro-inflammatory mediators in lipopolysaccharide (LPS)-stimulated murine N9 micreglia.METHODS The effects of PF11 on the NO production in activated microglial cells were assessed by Griess reaction.Western blotting was used to detect the protein phosphorylation levels of p38, JNK, ERK, IKKα/β,TAK1 and IκB-α.NF-κB activity was analyzed by using High-Content assay.RESULTS PF11 suppressed production of nitric oxide (NO), prostaglandin E2 (PGE2) and the pro-inflammatory cytokines, interleukin-1 β (IL-1β) in a concentration-dependent manner.PF11 significantly inhibited NF-κB translocation in LPS-stimulated N9 micreglia, this was associated with a decrease in the phosphorylation level of inhibitory κB-α (IκB-a).Furthermore, PF11 suppressed the phosphorylation of transforming growth factor β activated kinase-1 (TAK1) and inhibitor of κB kinase (IKK).Moreover, PF11 blocked signaling upstream of NF-κB activation by inhibiting extracellular signal-regulated kinases 1 and 2 (ERK1/2), c-Jun N-terminal kinase (JNK) and p38 MAPK.CONCLUSION Our results demonstrate that suppression of the NF-κB, MAPKs signaling pathways may inhibit LPS-induced NO and PGE2 production.Therefore, PF11 may have therapeutic potential for neurodegenerative diseases by inhibiting pro-inflammatory mediators and cytokine production in activated micreglia.