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Kim, Young Eun; Hwang, Chul Ju; Lee, Hee Pom; Kim, Chun Sik; Son, Dong Ju; Ham, Young Wan; Hellström, Mats; Han, Sang-Bae; Kim, Hee Sik; Park, Eun Kyung; Hong, Jin Tae
Neuropharmacology, 05/2017, Volume: 117Journal Article
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. •Neuroinflammation and amyloidogenesis are main symptoms of Alzheimer's disease.•NF-κB activation can induce the inflammation and amyloidogenesis pathways.•Punicalagin inhibits NF-κB activation through direct binding to its subunit P50.•Punicalagin reduces LPS-induced neuroinflammation and amyloidogenesis.•Punicalagin is a possible candidate for treating Alzheimer's disease.
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