A novel polysaccharide from Acorus tatarinowii protects against LPS-induced neuroinflammation and neurotoxicity by inhibiting TLR4-mediated MyD88/NF-κB and PI3K/Akt signaling pathways.

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.

journal_name

Int J Biol Macromol

authors

Zhong J,Qiu X,Yu Q,Chen H,Yan C

doi

10.1016/j.ijbiomac.2020.06.266

subject

Has Abstract

pub_date

2020-11-15 00:00:00

pages

464-475

eissn

0141-8130

issn

1879-0003

pii

S0141-8130(20)33719-3

journal_volume

163

pub_type

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