Pinocembrin protects human brain microvascular endothelial cells against fibrillar amyloid-β(1-40) injury by suppressing the MAPK/NF-κB inflammatory pathways.
Pinocembrin protects human brain microvascular endothelial cells against fibrillar amyloid-β(1-40) injury by suppressing the MAPK/NF-κB inflammatory pathways.
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DOI：
10.1155/2014/470393
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发表时间：
2014
影响因子：
--
通讯作者：
Du GH
中科院分区：
文献类型：
--
作者：
Liu R;Li JZ;Song JK;Sun JL;Li YJ;Zhou SB;Zhang TT;Du GH
阿尔茨海默病（AD）患者脑血管中β淀粉样蛋白（Aβ）肽的蓄积可能通过Aβ诱导的微血管内皮发病机制促进疾病进展。Pinocembrin已被证明在AD模型中具有治疗效果。这些效应与微血管功能的保护相关，但在Aβ损伤条件下对内皮细胞的影响尚不清楚。本研究旨在探讨松属素对纤维状Aβ 1−40（fAβ 1−40）损伤的人脑微血管内皮细胞（hBMEC）的保护作用及其机制。结果表明，fAβ 1−40诱导的hBMEC细胞毒性可以通过松属素治疗来挽救。松属素增加细胞活力，减少LDH的释放，并减轻核凝聚。其逆转机制可能与抑制炎症反应有关，包括抑制MAPK活化，下调磷酸化IKK水平，减轻IκBα降解，阻断NF-κB p65核转位，减少促炎细胞因子的释放。暴露于fAβ 1 - 40后，松属素对调节氧化还原失衡没有表现出明显的作用。总之，MAPK和NF-κB信号通路的抑制在fAβ 1−40诱导的hBMEC中的松属素抗炎中发挥重要作用。这可以作为阿尔茨海默病相关缺陷中BMEC保护的治疗剂。
Cerebrovascular accumulation of amyloid-β (Aβ) peptides in Alzheimer's disease (AD) may contribute to disease progression through Aβ-induced microvascular endothelial pathogenesis. Pinocembrin has been shown to have therapeutic effects in AD models. These effects correlate with preservation of microvascular function, but the effect on endothelial cells under Aβ-damaged conditions is unclear. The present study focuses on the in vitro protective effect of pinocembrin on fibrillar Aβ 1−40 (fAβ 1−40) injured human brain microvascular endothelial cells (hBMECs) and explores potential mechanisms. The results demonstrate that fAβ 1−40-induced cytotoxicity in hBMECs can be rescued by pinocembrin treatment. Pinocembrin increases cell viability, reduces the release of LDH, and relieves nuclear condensation. The mechanisms of this reversal from Aβ may be associated with the inhibition of inflammatory response, involving inhibition of MAPK activation, downregulation of phosphor-IKK level, relief of IκBα degradation, blockage of NF-κB p65 nuclear translocation, and reduction of the release of proinflammatory cytokines. Pinocembrin does not show obvious effects on regulating the redox imbalance after exposure to fAβ 1−40. Together, the suppression of MAPK and the NF-κB signaling pathways play a significant role in the anti-inflammation of pinocembrin in hBMECs subjected to fAβ 1−40. This may serve as a therapeutic agent for BMEC protection in Alzheimer's-related deficits.
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DOI：
10.1523/jneurosci.4686-08.2008
发表时间：
2008-12-10
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Han BH;Zhou ML;Abousaleh F;Brendza RP;Dietrich HH;Koenigsknecht-Talboo J;Cirrito JR;Milner E;Holtzman DM;Zipfel GJ
通讯作者：
Zipfel GJ
影响因子：
64.5
作者：
FRESHNEY, NW;RAWLINSON, L;SAKLATVALA, J
通讯作者：
SAKLATVALA, J
影响因子：
5.8
作者：
HODNICK, WF;DUVAL, DL;PARDINI, RS
通讯作者：
PARDINI, RS
影响因子：
2.9
作者：
Cainelli, Gianfranco;Angeloni, Cristina;Sinisi, Riccardo
通讯作者：
Sinisi, Riccardo
影响因子：
5.5
作者：
Giri, R;Selvaraj, S;Kalra, VK
通讯作者：
Kalra, VK