National Engineering Laboratory of Intelligent Food Technology and Equipment, Key Laboratory for Agro-Products Postharvest Handling of Ministry of Agriculture and Rural Affairs, Key Laboratory for Agro-Products Nutritional Evaluation of Ministry of Agriculture and Rural Affairs, Zhejiang Key Laboratory for Agro-Food Processing, Fuli Institute of Food Science, College of Biosystems Engineering and Food Science, Zhejiang University, Hangzhou 310058, China.
College of The First Clinical Medical, Guangzhou University of Chinese Medicine, Guangzhou 510006, China.
Int J Mol Sci. 2018 Apr 10;19(4):1135. doi: 10.3390/ijms19041135.
Nuclear factor erythroid 2-related factor 2 (Nrf2) is a key transcription factor against oxidative stress and neurodegenerative disorders. Phenylethanoid glycosides (PhGs; salidroside, acteoside, isoacteoside, and echinacoside) exhibit antioxidant and neuroprotective bioactivities. This study was performed to investigate the neuroprotective effect and molecular mechanism of PhGs. PhGs pretreatment significantly suppressed H₂O₂-induced cytotoxicity in PC12 cells by triggering the nuclear translocation of Nrf2 and reversing the downregulated protein expression of heme oxygenase 1 (HO-1), NAD(P)H quinone oxidoreductase 1 (NQO1), glutamate cysteine ligase-catalytic subunit (GCLC), and glutamate-cysteine ligase modifier subunit (GCLM). Nrf2 siRNA or HO-1 inhibitor zinc protoporphyrin (ZnPP) reduced the neuroprotective effect. PhGs showed potential interaction with the Nrf2 binding site in Kelch-like ECH-association protein 1 (Keap1). This result may support the hypothesis that PhGs are activators of Nrf2. We demonstrated the potential binding between PhGs and the Keap1-activated Nrf2/ARE pathway, and that PhGs with more glycosides had enhanced effects.
核因子红细胞 2 相关因子 2 (Nrf2) 是一种对抗氧化应激和神经退行性疾病的关键转录因子。苯乙醇苷类化合物 (PhGs；红景天苷、 乙酰紫堇醇苷、异乙酰紫堇醇苷和毛蕊花糖苷) 具有抗氧化和神经保护的生物活性。本研究旨在探讨 PhGs 的神经保护作用及其分子机制。PhGs 预处理可通过触发 Nrf2 的核易位并逆转血红素加氧酶 1 (HO-1)、NAD(P)H 醌氧化还原酶 1 (NQO1)、谷氨酸半胱氨酸连接酶催化亚基 (GCLC) 和谷氨酸-半胱氨酸连接酶修饰亚基 (GCLM) 下调的蛋白表达，显著抑制 H₂O₂诱导的 PC12 细胞毒性。Nrf2 siRNA 或 HO-1 抑制剂锌原卟啉 (ZnPP) 降低了神经保护作用。PhGs 与 Kelch 样 ECH 相关蛋白 1 (Keap1) 中的 Nrf2 结合位点具有潜在相互作用。这一结果可能支持 PhGs 是 Nrf2 激活剂的假说。我们证明了 PhGs 与 Keap1 激活的 Nrf2/ARE 途径之间的潜在结合，并且具有更多糖苷的 PhGs 具有增强的作用。
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