Laboratorio de Aminoácidos Excitadores, Instituto Nacional de Neurología y Neurocirugía, Insurgentes Sur 3877, 14269, Mexico City, Mexico.
Facultad de Ciencias, Universidad Nacional Autónoma de México, Mexico City, Mexico.
Neurotox Res. 2020 Feb;37(2):326-337. doi: 10.1007/s12640-019-00133-8. Epub 2019 Nov 26.
Caffeic acid (CA) is a hydroxycinnamic acid derivative and polyphenol with antioxidant and anti-inflammatory activities. The neuroprotective properties of CA still need detailed characterization in different biological models. Here, the antioxidant and neuroprotective effects of CA were compared in in vitro and in vivo neurotoxic models. Biochemical outcomes of cell dysfunction, oxidative damage, and transcriptional regulation were assessed in rat cortical slices, whereas endpoints of physiological stress and motor alterations were characterized in Caenorhabditis elegans (C. elegans). In rat cortical slices, CA (100 μM) prevented, in a differential manner, the loss of reductive capacity, the cell damage, and the oxidative damage induced by the excitotoxin quinolinic acid (QUIN, 100 μM), the pro-oxidant ferrous sulfate (FeSO, 25 μM), and the dopaminergic toxin 6-hydroxydopamine (6-OHDA, 100 μM). CA also restored the levels of nuclear factor erythroid 2-related factor 2/antioxidant response element (Nrf2/ARE; a master antioxidant regulatory pathway) binding activity affected by the three toxins. In wild-type (N2) of C. elegans, but not in the skn-1 KO mutant strain (worms lacking the orthologue of mammalian Nrf2), CA (25 mM) attenuated the loss of survival induced by QUIN (100 mM), FeSO (15 mM), and 6-OHDA (25 mM). Motor alterations induced by the three toxic models in N2 and skn-1 KO strains were prevented by CA in a differential manner. Our results suggest that (1) CA affords partial protection against different toxic insults in mammalian brain tissue and in C. elegans specimens; (2) the Nrf2/ARE binding activity participates in the protective mechanisms evoked by CA in the mammalian cortical tissue; (3) the presence of the orthologous skn-1 pathway is required in the worms for CA to exert protective effects; and (4) CA exerts antioxidant and neuroprotective effects through homologous mechanisms in different species.
咖啡酸（CA）是一种羟基肉桂酸衍生物和多酚，具有抗氧化和抗炎活性。CA 的神经保护特性仍需要在不同的生物模型中进行详细表征。在这里，比较了 CA 在体外和体内神经毒性模型中的抗氧化和神经保护作用。在大鼠皮质切片中评估了细胞功能障碍、氧化损伤和转录调节的生化结果，而在秀丽隐杆线虫（C. elegans）中则描述了生理应激和运动改变的终点。在大鼠皮质切片中，CA（100μM）以不同的方式防止了兴奋性毒素喹啉酸（QUIN，100μM）、促氧化剂硫酸亚铁（FeSO，25μM）和多巴胺能毒素 6-羟多巴胺（6-OHDA，100μM）诱导的还原能力丧失、细胞损伤和氧化损伤。CA 还恢复了三种毒素影响的核因子红细胞 2 相关因子 2/抗氧化反应元件（Nrf2/ARE；主要抗氧化调节途径）结合活性的水平。在野生型（N2）秀丽隐杆线虫中，但不在缺乏哺乳动物 Nrf2 同源物的 skn-1 KO 突变株（线虫）中，CA（25mM）减轻了 QUIN（100mM）、FeSO（15mM）和 6-OHDA（25mM）诱导的存活率丧失。CA 以不同的方式防止了三种毒性模型在 N2 和 skn-1 KO 菌株中诱导的运动改变。我们的结果表明：（1）CA 对哺乳动物脑组织和秀丽隐杆线虫标本中的不同毒性损伤提供部分保护；（2）Nrf2/ARE 结合活性参与了 CA 在哺乳动物皮质组织中引发的保护机制；（3）线虫中存在同源的 skn-1 途径是 CA 发挥保护作用所必需的；（4）CA 通过不同物种中的同源机制发挥抗氧化和神经保护作用。
