Lychee seed polyphenol protects the blood-brain barrier through inhibiting Aβ(25-35)-induced NLRP3 inflammasome activation via the AMPK/mTOR/ULK1-mediated autophagy in bEnd.3 cells and APP/PS1 mice.
Rui XiongXiao-Gang ZhouYong TangJian-Ming WuYue-Shan SunJin-Feng TengRong PanBetty Yuen-Kwan LawYa ZhaoWen-Qiao QiuXiu-Ling WangSha LiuYi-Ling WangLu YuChong-Lin YuQi-Bing MeiDa-Lian QinXiliang DuPublished in: Phytotherapy research : PTR (2020)
Blood-brain barrier (BBB) dysfunction has been implicated in Alzheimer's disease (AD) and is closely linked to the release of proinflammatory cytokines in brain capillary endothelial cells. We have previously reported that lychee seed polyphenols (LSP) exerted anti-neuroinflammatory effect. In this study, we aimed to explore the protective effect of LSP on BBB integrity. The monolayer permeability of bEnd.3 cells, and the mRNA level and protein expression of tight junction proteins (TJs), including Claudin 5, Occludin, and ZO-1, were examined. In addition, the inhibition of Aβ(25-35)-induced NLRP3 inflammasome activation, and the autophagy induced by LSP were investigated by detecting the expression of NLRP3, caspase-1, ASC, LC3, AMPK, mTOR, and ULK1. Furthermore, the cognitive function and the expression of TJs, NLRP3, caspase-1, IL-1β, and p62 were determined in APP/PS1 mice. The results showed that LSP significantly decreased the monolayer permeability and inhibited the NLRP3 inflammasome in Aβ(25-35)-induced bEnd3 cells. In addition, LSP induced autophagy via the AMPK/mTOR/ULK1 pathway in bEnd.3 cells, and improved the spatial learning and memory function, increased the TJs expression, and inhibited the expression of NLRP3, caspase-1, IL-1β, and p62 in APP/PS1 mice. Therefore, LSP protects BBB integrity in AD through inhibiting Aβ(25-35)-induced NLRP3 inflammasome activation via the AMPK/mTOR/ULK1-mediated autophagy.
Keyphrases
- nlrp inflammasome
- induced apoptosis
- blood brain barrier
- endoplasmic reticulum stress
- cell death
- signaling pathway
- high glucose
- cell cycle arrest
- oxidative stress
- endothelial cells
- diabetic rats
- poor prognosis
- skeletal muscle
- cell proliferation
- drug induced
- binding protein
- type diabetes
- cerebral ischemia
- long non coding rna
- high fat diet induced
- adipose tissue
- mass spectrometry
- insulin resistance
- vascular endothelial growth factor