Pérez Rebeca, Burgos Viviana, Marín Víctor, Camins Antoni, Olloquequi Jordi, González-Chavarría Iván, Ulrich Henning, Wyneke Ursula, Luarte Alejandro, Ortiz Leandro, Paz Cristian
Laboratory of Natural Products & Drug Discovery, Center CEBIM, Department of Basic Sciences, Faculty of Medicine, Universidad de La Frontera, Temuco 4780000, Chile.
Departamento de Ciencias Biológicas y Químicas, Facultad de Recursos Naturales, Universidad Católica de Temuco, Rudecindo Ortega, Temuco 4780000, Chile.
Antioxidants (Basel). 2023 Jul 27;12(8):1500. doi: 10.3390/antiox12081500.
Neurodegenerative disorders are characterized by a progressive process of degeneration and neuronal death, where oxidative stress and neuroinflammation are key factors that contribute to the progression of these diseases. Therefore, two major pathways involved in these pathologies have been proposed as relevant therapeutic targets: The nuclear transcription factor erythroid 2 (Nrf2), which responds to oxidative stress with cytoprotecting activity; and the nuclear factor NF-κB pathway, which is highly related to the neuroinflammatory process by promoting cytokine expression. Caffeic acid phenethyl ester (CAPE) is a phenylpropanoid naturally found in propolis that shows important biological activities, including neuroprotective activity by modulating the Nrf2 and NF-κB pathways, promoting antioxidant enzyme expression and inhibition of proinflammatory cytokine expression. Its simple chemical structure has inspired the synthesis of many derivatives, with aliphatic and/or aromatic moieties, some of which have improved the biological properties. Moreover, new drug delivery systems increase the bioavailability of these compounds in vivo, allowing its transcytosis through the blood-brain barrier, thus protecting brain cells from the increased inflammatory status associated to neurodegenerative and psychiatric disorders. This review summarizes the biosynthesis and chemical synthesis of CAPE derivatives, their miscellaneous activities, and relevant studies (from 2010 to 2023), addressing their neuroprotective activity in vitro and in vivo.
神经退行性疾病的特征是神经元进行性变性和死亡，其中氧化应激和神经炎症是导致这些疾病进展的关键因素。因此，参与这些病理过程的两条主要途径已被提议作为相关的治疗靶点：核转录因子红细胞2（Nrf2），它通过细胞保护活性对氧化应激作出反应；以及核因子κB途径，它通过促进细胞因子表达与神经炎症过程高度相关。咖啡酸苯乙酯（CAPE）是一种天然存在于蜂胶中的苯丙烷类化合物，具有重要的生物活性，包括通过调节Nrf2和NF-κB途径、促进抗氧化酶表达和抑制促炎细胞因子表达来发挥神经保护活性。其简单的化学结构激发了许多衍生物的合成，这些衍生物带有脂肪族和/或芳香族部分，其中一些改善了生物学性质。此外，新的药物递送系统提高了这些化合物在体内的生物利用度，使其能够通过血脑屏障进行转胞吞作用，从而保护脑细胞免受与神经退行性疾病和精神疾病相关的炎症状态增加的影响。本综述总结了CAPE衍生物的生物合成和化学合成、它们的多种活性以及相关研究（2010年至2023年），阐述了它们在体外和体内的神经保护活性。
