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Title 

Inhibitory effect of punicalagin on lipopolysaccharide-induced neuroinflammation, oxidative stress and memory impairment via inhibition of nuclear factor-kappaB

Authors 

Y E KimC J HwangH P LeeC S KimD J SonY W HamM HellstromS B HanHee-Sik KimE K ParkJ T Hong

Publisher 

Elsevier

Issue Date 

2017

Citation 

Neuropharmacology

Keywords 

Alzheimer's diseaseAmyloidogenesisLipopolysaccharideMemory impairmentNeuroinflammationPomegranatePunicalagin

Abstract 

Neuroinflammation is significant in the pathogenesis and development of Alzheimer's disease (AD). Previously, we showed lipopolysaccharide (LPS)-induced neuroinflammation caused memory impairment. We investigated the possible preventive effects of punicalagin (PUN), a component of pomegranate, on memory deficiency caused by LPS, along with the fundamental mechanisms. LPS-treated cultured astrocytes and microglial BV-2?cells were investigated for anti-neuroinflammatory effects of PUN. PUN (1.5?mg/kg) ameliorates LPS (250?μg/kg daily 7 times)-induced memory impairment as well as prevents the LPS-induced expression of inflammatory proteins. In in?vitro study, we also found that PUN (1?μg/ml) inhibited the LPS-(10, 20 and 50?μM) induced expression of iNOS and Cox-2 as well as the production of ROS, NO, TNF-α and IL-1β. PUN also suppress activation of NF-κB via inhibition of IκB degradation as well as p50 and p65 translocation into the nucleus in LPS treated mouse brain and cultured astrocytes and microglial BV-2?cells. Consistent with the inhibitory effect on neuro inflammation, PUN inhibited LPS-induced Aβ1-42 generation through down-regulation of APP and BACE1 expression in in?vivo and in?vitro study. Moreover, PUN directly binds to NF-κB subunit p50 evidenced by a docking model and pull down assay. These results suggest that PUN inhibits LPS-induced memory impairment via anti-inflammatory and anti-amylogenic mechanisms through inhibition of NF-κB activation.

ISSN 

0028-3908

Link 

http://dx.doi.org/10.1016/j.neuropharm.2017.01.025

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2019-05-02


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