Icariside II inhibits lipopolysaccharide-induced inflammation and amyloid production in rat astrocytes by regulating IKK/IkappaB/NF-kappaB/BACE1 signaling pathway.
Icariside II inhibits lipopolysaccharide-induced inflammation and amyloid production in rat astrocytes by regulating IKK/IkappaB/NF-kappaB/BACE1 signaling pathway.
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Icariside II 通过调节 IKK/IkappaB/NF-kappaB/BACE1 信号通路抑制大鼠星形胶质细胞中脂多糖诱导的炎症和淀粉样蛋白的产生。
DOI：
10.1038/s41401-019-0300-2
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发表时间：
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影响因子：
8.2
通讯作者：
Gong Qi-Hai
中科院分区：
文献类型：
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作者：
Zheng Yong;Deng Yan;Gao Jian-Mei;Lv Chun;Lang Ling-Hu;Shi Jing-Shan;Yu Chang-Yin;Gong Qi-Hai
β-淀粉样蛋白（Aβ）是星形胶质细胞活化和神经炎症的诱导因素之一，也是阿尔茨海默病（AD）发生的关键因素。 Icariside II (ICS II) 是从传统中药淫羊藿中分离出来的活性成分，可通过调节 NF-κB 信号通路减轻脂多糖 (LPS) 诱导的神经炎症。在本研究中，我们研究了 ICS II 对 LPS 诱导的星形胶质细胞活化和 Aβ 积累的影响。原代大鼠星形胶质细胞用ICS II（5、10和20μM）或地塞米松（DXMS，1μM）预处理1小时，然后用LPS再处理24小时。我们发现ICS II预处理剂量依赖性地降低了星形胶质细胞中肿瘤坏死因子-α（TNF-α）、白细胞介素-1β（IL-1β）、诱导型一氧化氮合酶（iNOS）、环氧合酶-2（COX-2）的水平。此外，ICS II不仅对LPS诱导的IκB-α降解和NF-κB活化发挥抑制作用，而且还降低星形胶质细胞中Aβ1-40、Aβ1-42、淀粉样前体蛋白（APP）和β分泌酶1（BACE1）的水平。有趣的是，分子对接显示 ICS II 可能直接与 BACE1 结合。结论是ICS II作为治疗AD等神经炎症相关疾病的新治疗剂具有潜在价值。
β-amyloid (Aβ) is one of the inducing factors of astrocytes activation and neuroinflammation, and it is also a crucial factor for the development of Alzheimer’s disease (AD). Icariside II (ICS II) is an active component isolated from a traditional Chinese herbEpimedium, which has shown to attnuate lipopolysaccharide (LPS)-induced neuroinflammation through regulation of NF-κB signaling pathway. In this study we investigated the effects of ICS II on LPS-induced astrocytes activation and Aβ accumulation. Primary rat astrocytes were pretreated with ICS II (5, 10, and 20 μM) or dexamethasone (DXMS, 1 μM) for 1 h, thereafter, treated with LPS for another 24 h. We found that ICS II pretreatment dose dependently mitigated the levels of tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2) in the astrocytes. Moreover, ICS II not only exerted the inhibitory effect on LPS-induced IκB-α degradation and NF-κB activation, but also decreased the levels of Aβ1–40, Aβ1–42, amyloid precursor protein (APP) and beta secretase 1 (BACE1) in the astrocytes. Interestingly, molecular docking revealed that ICS II might directly bind to BACE1. It is concluded that ICS II has potential value as a new therapeutic agent to treat neuroinflammation-related diseases, such as AD.