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Neuropharmacology. 2017 May 1;117:21-32. doi: 10.1016/j.neuropharm.2017.01.025. Epub 2017 Jan 26.

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

Author information

1
College of Pharmacy and Medical Research Center, Chungbuk National University, 194-31, Osongsangmyeong1-ro, Heungdeok-gu, Cheongju, Chungbuk 28160, Republic of Korea.
2
Bio-Interchange Co, 194-41, Osongsanengmyeong 1-ro, Heungdeock-gu, Cheongju, Chungbuk 28160, Republic of Korea.
3
Department of Chemistry, Utah Valley University, 800 West University Parkway, Orem, UT 84508, USA.
4
Laboratory for Transplantation and Regenerative Medicine, Department of Obstetrics and Gynecology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
5
Sustainable Bioresource Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), 125 Gawhak-ro, Yuseoung, Daejeon 305-806, Republic of Korea.
6
Department of Obstetrics and Gynecology, College of Medicine, Daejeon St. Mary's Hospital, The Catholic University of Korea, 64 Daeheung-ro, Jung-gu, Daejeon 34943, Republic of Korea. Electronic address: guevara614@catholic.ac.kr.
7
College of Pharmacy and Medical Research Center, Chungbuk National University, 194-31, Osongsangmyeong1-ro, Heungdeok-gu, Cheongju, Chungbuk 28160, Republic of Korea. Electronic address: jinthong@chungbuk.ac.kr.

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.

KEYWORDS:

Alzheimer's disease; Amyloidogenesis; Lipopolysaccharide; Memory impairment; Neuroinflammation; Pomegranate; Punicalagin

[Indexed for MEDLINE]

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