Chicoric acid supplementation prevents systemic inflammation- induced memory impairment and amyloidogenesis via inhibition of NF-κB
Chicoric acid supplementation prevents systemic inflammation- induced memory impairment and amyloidogenesis via inhibition of NF-κB
复制标题
补充菊苣酸可通过抑制 NF-κ B 预防全身炎症引起的记忆障碍和淀粉样蛋白生成
DOI：
10.1096/fj.201601071r
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发表时间：
2017-04-01
期刊：
影响因子：
4.8
通讯作者：
Liu, Xuebo
中科院分区：
文献类型：
--
作者：
Liu, Qian;Chen, Yuwei;Liu, Xuebo
菊苣酸（CA）是从菊苣和紫锥花植物（Echinacea purpurea）中提取的天然酚酸，被认为是一种具有强大抗氧化和抗肥胖活性的营养保健品。我们研究了 CA 对全身炎症诱导的神经炎症、淀粉样蛋白生成和认知障碍的抑制作用。 C57BL/6J 小鼠用含 0.05% CA 的饮用水处理 45 d。然后通过腹膜内注射脂多糖（LPS）来治疗小鼠。通过行为测试和组织学检查发现，CA可以预防LPS引起的记忆障碍和神经元损失。此外，还检测到中枢神经系统中的淀粉样蛋白生成。结果表明，CA 可以阻止 LPS 诱导的β淀粉样蛋白（1-42 特异性）（A beta(1-42)）积累、淀粉样蛋白前体蛋白和神经元 β 分泌酶 1 (BACE1) 水平的增加，以及小鼠大脑中的平衡胆碱能系统。此外，CA 通过抑制 MAPK 和 NF-κ B 通路来下调 LPS 诱导的神经胶质细胞过度激活。因此，CA 降低了小鼠大脑和 BV2 小胶质细胞中 NF-κ B 转录调节炎症介质和细胞因子的水平，例如 iNOS、环氧合酶-2 (COX-2)、IL-1 β 和 TNF-α。这些结果表明，CA 通过抑制 NF-kB 转录途径减轻 LPS 引发的记忆损伤和淀粉样蛋白生成，这表明 CA 可能是治疗阿尔茨海默病等神经炎症相关疾病的一种合理的治疗干预措施。-Liu, Q.、Chen, Y.、Shen, C.、Xiao, Y.、Wang, Y.、Liu, Z.、Liu, X. 补充菊苣酸可通过抑制NF-kB。 FASEB J. 31, 1494-1507 (2017)。 www.fasebj.org
Chicoric acid (CA), a natural phenolic acid extracted from chicory and the echinacea (purple coneflower) plant (Echinacea purpurea), has been regarded as a nutraceutical that has powerful antioxidant and antiobesity activities. We investigated the inhibitory effects of CA on systemic inflammation-induced neuroinflammation, amyloidogenesis, and cognitive impairment. C57BL/6J mice were treated with 0.05% CA in the drinking water for 45 d. The mice were then treated by intraperitoneal injection of lipopolysaccharide (LPS). It was found that CA prevented LPS-induced memory impairment and neuronal loss through behavioral tests and histological examination. Furthermore, amyloidogenesis in the CNS was detected. The results showed that CA prevented LPS-induced increases in amyloid beta (1-42 specific) (A beta(1-42)) accumulation, levels of amyloid precursor protein, and neuronal beta-secretase 1 (BACE1), aswell as the equilibrium cholinergic system in mouse brain. Moreover, CA down regulated LPS-induced glial overactivation by inhibiting the MAPK and NF-kappa B pathway. Consequently, CA reduced the levels of NF-kappa B transcriptionally regulated inflammatory mediators and cytokines such as iNOS, cyclooxygenase-2 (COX-2), IL-1 beta, and TNF-alpha in both mouse brain and BV2 microglial cells. These results demonstrated that CA alleviated memory impairment and amyloidogenesis triggered by LPS through suppressing NF-kB transcriptional pathway, suggesting that CA might be a plausible therapeutic intervention for neuroinflammationrelated diseases such as Alzheimer disease.-Liu, Q., Chen, Y., Shen, C., Xiao, Y., Wang, Y., Liu, Z., Liu, X. Chicoric acid supplementation prevents systemic inflammation-induced memory impairment and amyloidogenesis via inhibition of NF-kB. FASEB J. 31, 1494-1507 (2017). www.fasebj.org