Cyanidin is polyphenolic pigment found in plants. We have previously demonstrated that cyanidin protects nerve cells against Aβ_25-35-induced toxicity by decreasing oxidative stress and attenuating apoptosis mediated by both the mitochondrial apoptotic pathway and the ER stress pathway. To further elucidate the molecular mechanisms underlying the neuroprotective effects of cyanidin, we investigated the effects of cyanidin on neuroinflammation mediated by the TLR4/NOX4 pathway in Aβ_25-35-treated human neuroblastoma cell line (SK-N-SH). SK-N-SH cells were exposed to Aβ_25-35 (10 μmol/L) for 24 h. Pretreatment with cyanidin (20 μmol/L) or NAC (20 μmol/L) strongly inhibited the NF-κB signaling pathway in the cells evidenced by suppressing the degradation of IκBα, translocation of the p65 subunit of NF-κB from the cytoplasm to the nucleus, and thereby reducing the expression of iNOS protein and the production of NO. Furthermore, pretreatment with cyanidin greatly promoted the translocation of the Nrf2 protein from the cytoplasm to the nucleus; upregulating cytoprotective enzymes, including HO-1, NQO-1 and GCLC; and increased the activity of SOD enzymes. Pretreatment with cyanidin also decreased the expression of TLR4, directly improved intracellular ROS levels and regulated the activity of inflammation-related downstream pathways including NO production and SOD activity through TLR4/NOX4 signaling. These results demonstrate that TLR4 is a primary receptor in SK-N-SH cells, by which Aβ_25-35 triggers neuroinflammation, and cyanidin attenuates Aβ-induced inflammation and ROS production mediated by the TLR4/NOX4 pathway, suggesting that inhibition of TLR4 by cyanidin could be beneficial in preventing neuronal cell death in the process of Alzheimer's disease.

中文翻译：

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氰胺素通过抑制人成神经细胞瘤细胞中TLR4 / NOX4下游的NF-κB活性来减轻Aβ25-35诱导的神经炎症。

氰胺素是植物中发现的多酚颜料。先前我们已经证明，花青素通过降低氧化应激并减弱线粒体凋亡途径和ER应激途径介导的凋亡，从而保护神经细胞免受_Aβ25-35诱导的毒性。为了进一步阐明潜在花青素的神经保护作用的分子机制，我们研究了通过在Aβ的TLR4 / NOX4通路介导的神经炎症花青素的效果_25-35 -处理的人类神经母细胞瘤细胞系（SK-N-SH）。SK-N-SH细胞暴露于_Aβ25-35（10μmol/ L）进行24小时。用花青素（20μmol/ L）或NAC（20μmol/ L）预处理可强烈抑制细胞中的NF-κB信号通路，这可通过抑制IκBα的降解，NF-κB的p65亚基从细胞质到细胞内的转运来证明。核，从而减少iNOS蛋白的表达和NO的产生。此外，用花青素进行的预处理大大促进了Nrf2蛋白从细胞质到细胞核的转运。上调细胞保护酶，包括HO-1，NQO-1和GCLC；并增加了SOD酶的活性。用花青素预处理还降低了TLR4的表达，直接改善了细胞内ROS的水平，并通过TLR4 / NOX4信号传导调节了炎症相关下游途径的活性，包括NO的产生和SOD的活性。_25-35触发神经炎症，并且花青素减轻Aβ诱导的由TLR4 / NOX4途径介导的炎症和ROS的产生，这表明花青素抑制TLR4可能有助于预防阿尔茨海默氏病过程中神经元细胞的死亡。