Departamento de Farmacología, Farmacognosia y Botánica, Facultad de Farmacia, Universidad Complutense de Madrid, Plaza Ramón y Cajal s/n, Ciudad Universitaria, 28040 Madrid, Spain.
Int J Mol Sci. 2023 Feb 13;24(4):3748. doi: 10.3390/ijms24043748.
Neurodegenerative diseases (NDs) affect the West due to the increase in life expectancy. Nervous cells accumulate oxidative damage, which is one of the factors that triggers and accelerates neurodegeneration. However, cells have mechanisms that scavenge reactive oxygen species (ROS) and alleviate oxidative stress (OS). Many of these endogenous antioxidant systems are regulated at the gene expression level by the transcription factor Nrf2 (nuclear factor erythroid 2-related factor 2). In the presence of prooxidant conditions, Nrf2 translocates to the nucleus and induces the transcription of genes containing ARE (antioxidant response element). In recent years, there has been an increase in the study of the Nrf2 pathway and the natural products that positively regulate it to reduce oxidative damage to the nervous system, both in in vitro models with neurons and microglia subjected to stress factors and in vivo models using mainly murine models. Quercetin, curcumin, anthocyanins, tea polyphenols, and other less studied phenolic compounds such as kaempferol, hesperetin, and icariin can also modulate Nrf2 by regulating several Nrf2 upstream activators. Another group of phytochemical compounds that upregulate this pathway are terpenoids, including monoterpenes (aucubin, catapol), diterpenes (ginkgolides), triterpenes (ginsenosides), and carotenoids (astaxanthin, lycopene). This review aims to update the knowledge on the influence of secondary metabolites of health interest on the activation of the Nrf2 pathway and their potential as treatments for NDs.
神经退行性疾病（NDs）由于预期寿命的延长而在西方流行。神经细胞积累氧化损伤，这是触发和加速神经退行性变的因素之一。然而，细胞有清除活性氧（ROS）和减轻氧化应激（OS）的机制。许多这些内源性抗氧化系统在基因表达水平上受转录因子 Nrf2（红细胞生成素 2 相关因子 2）调节。在存在促氧化剂条件下，Nrf2 易位到细胞核并诱导含有 ARE（抗氧化反应元件）的基因转录。近年来，人们对 Nrf2 途径及其积极调节的天然产物的研究有所增加，以减少神经系统的氧化损伤，无论是在神经元和小胶质细胞受到应激因素的体外模型中，还是在主要使用鼠模型的体内模型中。槲皮素、姜黄素、花青素、茶多酚和其他研究较少的酚类化合物，如山柰酚、橙皮苷和淫羊藿苷，也可以通过调节几种 Nrf2 上游激活剂来调节 Nrf2。上调该途径的另一组植物化学化合物是萜类化合物，包括单萜（aucubin、catapol）、二萜（银杏内酯）、三萜（人参皂苷）和类胡萝卜素（虾青素、番茄红素）。本综述旨在更新关于具有健康益处的次生代谢物对 Nrf2 途径激活的影响及其作为神经退行性疾病治疗方法的潜力的知识。
