Abstract:
Oxidative stress can damage neuronal cells, greatly contributing to neurodegenerative diseases (NDs). In this study, the protective activity of arzanol, a natural prenylated α-pyrone-phloroglucinol heterodimer, was evaluated against the H2O2-induced oxidative damage in trans-retinoic acid-differentiated (neuron-like) human SH-SY5Y cells, widely used as a neuronal cell model of neurological disorders. The pre-incubation (for 2 and 24 h) with arzanol (5, 10, and 25 μM) significantly preserved differentiated SH-SY5Y cells from cytotoxicity (MTT assay) and morphological changes induced by 0.25 and 0.5 mM H2O2. Arzanol reduced the generation of reactive oxygen species (ROS) induced by 2 h oxidation with H2O2 0.5 mM, established by 2\',7\'-dichlorodihydrofluorescein diacetate assay. The 2 h incubation of differentiated SH-SY5Y cells with H2O2 determined a significant increase in the number of apoptotic cells versus control cells, evaluated by propidium iodide fluorescence assay (red fluorescence) and NucView® 488 assay (green fluorescence). Arzanol pre-treatment (2 h) exerted a noteworthy significant protective effect against apoptosis. In addition, arzanol was tested, for comparison, in undifferentiated SH-SY5Y cells for cytotoxicity and its ability to protect against H2O2-induced oxidative stress. Furthermore, the PubChem database and freely accessible web tools SwissADME and pkCSM-pharmacokinetics were used to assess the physicochemical and pharmacokinetic properties of arzanol. Our results qualify arzanol as an antioxidant agent with potential neuroprotective effects against neuronal oxidative stress implicated in NDs.
摘要:
氧化应激可以损伤神经元细胞,极大地促进神经退行性疾病(ND)。在这项研究中,阿维素的保护活性,天然异戊烯化α-吡喃酮-间苯三酚异二聚体,对反式维甲酸分化(神经元样)人SH-SY5Y细胞中H2O2诱导的氧化损伤进行了评估,广泛用作神经系统疾病的神经元细胞模型。与阿维素(5、10和25μM)的预孵育(2和24小时)显着保留了分化的SH-SY5Y细胞免受0.25和0.5mMH2O2诱导的细胞毒性(MTT测定)和形态变化。Arzanol减少了0.5mMH2O22h氧化诱导的活性氧(ROS)的产生,由2\'建立,7'-二氯二氢荧光素二乙酸盐测定。分化的SH-SY5Y细胞与H2O2孵育2小时后,与对照细胞相比,凋亡细胞的数量显着增加,通过碘化丙啶荧光测定(红色荧光)和NucView®488测定(绿色荧光)进行评估。Arzanol预处理(2小时)对细胞凋亡具有显着的保护作用。此外,阿维素进行了测试,为了比较,在未分化的SH-SY5Y细胞中具有细胞毒性及其抵抗H2O2诱导的氧化应激的能力。此外,使用PubChem数据库和免费访问的网络工具SwissADME和pkCSM-药代动力学来评估阿维素的理化和药代动力学特性.我们的结果证明,阿维素是一种抗氧化剂,对与ND有关的神经元氧化应激具有潜在的神经保护作用。