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高良姜果实通过 PI3K/AKT/NF-κB 信号通路缓解 LPS 诱导的认知障碍。

Alpinae Oxyphyllae Fructus alleviated LPS-induced cognitive impairments via PI3K/AKT/NF-κB signaling pathway.

机构信息

School of Functional Food and Wine, Shenyang Pharmaceutical University, Shenyang, China.

School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang, China.

出版信息

Environ Toxicol. 2022 Mar;37(3):489-503. doi: 10.1002/tox.23415. Epub 2021 Dec 7.

DOI:10.1002/tox.23415
PMID:34874107
Abstract

Herein, we aim to investigate the effect of Alpinae Oxyphyllae Fructus (AOF) on cognitive impairments and neuroinflammation in a lipopolysaccharide (LPS)-induced models of AD. Mice were injected intracerebroventricularly with LPS, and then administrated AOF using a gavage for 6 weeks. Spatial working memory was assessed using the Y-maze and Morris water maze test, whereas the levels of PI3K, AKT, p-AKT, p-GSK3β, GSK3β, NF-κB, IL-1β, IL-6, and TNF-α were evaluated using western blot and ELISA assay. Our data showed that AOF was able to significantly alleviate the memory decline in LPS-induced AD mice. Moreover, AOF was able to protect neurons through the PI3K/AKT signaling pathway and significantly decrease NF-κB, IL-6, IL-1β, and TNF-α levels in the hippocampal and cortex tissues, which were reversed through the use of LY294002. Additionally, we discovered that AOF could significantly decrease the high expression of cytokines as well as the expression and translocation of NF-κB induced by LPS in PC12 cells. These results demonstrate the anti-neuroinflammatory effect of AOF in both cell and animal models of AD, thereby slowing down the process and development of the disease.

摘要

在此,我们旨在研究高良姜果实(AOF)对脂多糖(LPS)诱导的 AD 模型中认知障碍和神经炎症的影响。通过脑室内注射 LPS,然后用灌胃法给予 AOF,共 6 周。使用 Y 迷宫和 Morris 水迷宫测试评估空间工作记忆,而使用 Western blot 和 ELISA 测定评估 PI3K、AKT、p-AKT、p-GSK3β、GSK3β、NF-κB、IL-1β、IL-6 和 TNF-α 的水平。我们的数据表明,AOF 能够显著减轻 LPS 诱导的 AD 小鼠的记忆减退。此外,AOF 通过 PI3K/AKT 信号通路保护神经元,并显著降低海马和皮质组织中 NF-κB、IL-6、IL-1β 和 TNF-α 的水平,这种作用可通过 LY294002 逆转。此外,我们发现 AOF 可以显著降低 LPS 诱导的 PC12 细胞中细胞因子的高表达以及 NF-κB 的表达和易位。这些结果表明 AOF 在 AD 的细胞和动物模型中具有抗神经炎症作用,从而减缓疾病的进程和发展。

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