Abstract

Our previous study has indicated that a crude polysaccharide derived from Acorus tatarinowii , AT50, remarkably improves learning and memory in scopolamine-induced amnesic mice and prevents the release of inflammatory mediators. To further explore the bioactive constituents of AT50, a novel polysaccharide (ATP50-3) was purified, and its anti-neuroinflammatory effects and underlying mechanisms were investigated. ATP50-3 significantly reduced abnormal elevation of inflammatory mediators in lipopolysaccharide (LPS)-induced proinflammatory BV2 cells in vitro and inhibited the activation of nuclear factor kappa B (NF-κB). Moreover, ATP50-3 down-regulated LPS-induced protein levels of Toll-like receptor 4 (TLR4), myeloid differentiation primary response protein (MyD88), p-PI3K (phosphoinositide 3-kinase), and p-Akt (protein kinase B). Further experiments demonstrated that TAK242 (a TLR4 inhibitor) and LY294002 (a PI3K inhibitor) remarkably augmented ATP50-3's down-regulation on LPS-induced proinflammatory mediators. Importantly, ATP50-3 provided neuroprotection against neuroinflammation-induced neurotoxicity in primary cortical and hippocampal neurons by mitigating overproduction of reactive oxygen species and damage to the mitochondrial membrane potential (MMP). Taken together, our findings suggest that ATP50-3 exerts anti-neuroinflammatory and neuroprotective effects through modulation of TLR4-mediated MyD88/NF-κB and PI3K/Akt signaling pathways.