Department "Pharmacology, Pharmacotherapy and Toxicology", Faculty of Pharmacy, Medical University of Sofia, 1000 Sofia, Bulgaria.
Department of Pharmacognosy, Faculty of Pharmacy, Medical University of Sofia, 1000 Sofia, Bulgaria.
Int J Mol Sci. 2024 Sep 11;25(18):9805. doi: 10.3390/ijms25189805.
Oxidative stress exerts multiple disruptive effects on cellular morphology and function and is a major detriment to age-related and pathological neurodegenerative processes. The present study introduces an evaluative and comparative investigation of the antioxidant and cytoprotective properties of a extract and its major constituent 3,5-dicaffeoylquinic acid (DiCQA) in an in vitro model of HO-induced neurotoxicity. Using validated in vitro and in silico approaches, we established the presence and concentration dynamics of cellular protection in a 24 h pretreatment regimen with the natural products. The conducted cytotoxicity studies and the automated Chou-Talalay analysis for studying drug interactions demonstrated a strong antagonistic effect of the tested substances against oxidative stimuli in an "on demand" manner, prevailing at the higher end of the concentration range. These findings were further supported by the proteomic characterization of the treatment samples, accounting for a more distinct neuroprotection provided by the pure polyphenol 3,5-DiCQA.
氧化应激对细胞形态和功能产生多种破坏作用，是与年龄相关和病理性神经退行性过程的主要危害。本研究采用 HO 诱导的神经毒性体外模型，对 提取物及其主要成分 3,5-二咖啡酰奎尼酸（DiCQA）的抗氧化和细胞保护特性进行了评估和比较。使用经过验证的体外和计算方法，我们在 24 小时预处理方案中确定了天然产物存在和细胞保护的浓度动态。进行的细胞毒性研究和用于研究药物相互作用的自动 Chou-Talalay 分析表明，测试物质对氧化刺激具有强烈的拮抗作用，以“按需”方式在浓度范围的较高端占主导地位。这些发现得到了治疗样本的蛋白质组学特征的进一步支持，纯多酚 3,5-DiCQA 提供了更明显的神经保护作用。
