State Key Laboratory of Applied Organic Chemistry and College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou, 730000, China.
State Key Laboratory of Applied Organic Chemistry and College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou, 730000, China; State Key Laboratory of Bioreactor Engineering, Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai, 200237, China.
Arch Biochem Biophys. 2021 Jul 30;706:108857. doi: 10.1016/j.abb.2021.108857. Epub 2021 Mar 26.
Accumulating evidence has demonstrated that cellular antioxidant systems play essential roles in retarding oxidative stress-related diseases, such as Parkinson's disease. Because nuclear factor erythroid 2-related factor 2 (Nrf2) is a chief regulator of cellular antioxidant systems, small molecules with Nrf2-activating ability may be promising neuroprotective agents. Avenanthramide-2c (Aven-2c), avenanthramide-2f (Aven-2f) and avenanthramide-2p (Aven-2p) are the most abundant avenanthramides in oats, and they have been documented to possess multiple pharmacological benefits. In this work, we synthesized these three compounds and evaluated their cytoprotective effect against oxidative stress-induced PC12 cell injuries. Aven-2c displayed the best protective potency among them. Aven-2c conferred protection on PC12 cells by scavenging free radicals and activating the Nrf2-ARE signaling pathway. Pretreatment of PC12 cells with Aven-2c efficiently enhanced Nrf2 nuclear accumulation and evoked the expression of a set of cytoprotective molecules. The mechanistic study also supports that Nrf2 activation is the molecular basis for the cellular action of Aven-2c. Collectively, this study demonstrates that Aven-2c is a potent Nrf2 agonist, shedding light on the potential usage of Aven-2c in the treatment of neuroprotective diseases.
越来越多的证据表明，细胞抗氧化系统在延缓氧化应激相关疾病（如帕金森病）方面发挥着重要作用。由于核因子红细胞 2 相关因子 2（Nrf2）是细胞抗氧化系统的主要调节因子，因此具有 Nrf2 激活能力的小分子可能是有前途的神经保护剂。燕麦中含量最丰富的三种燕麦酰胺是 avenanthramide-2c（Aven-2c）、avenanthramide-2f（Aven-2f）和 avenanthramide-2p（Aven-2p），它们已被证明具有多种药理作用。在这项工作中，我们合成了这三种化合物，并评估了它们对氧化应激诱导的 PC12 细胞损伤的细胞保护作用。Aven-2c 在它们中显示出最好的保护效力。Aven-2c 通过清除自由基和激活 Nrf2-ARE 信号通路来保护 PC12 细胞。Aven-2c 预处理 PC12 细胞可有效增强 Nrf2 核积累并诱导一组细胞保护分子的表达。该机制研究还支持 Nrf2 激活是 Aven-2c 细胞作用的分子基础。总之，这项研究表明 Aven-2c 是一种有效的 Nrf2 激动剂，为 Aven-2c 在神经保护疾病治疗中的潜在用途提供了依据。
