Department of Genetics and Bioengineering, Faculty of Engineering and Architecture, Yeditepe University, Istanbul, Turkey.
Department of Genetics and Bioengineering, Faculty of Engineering and Architecture, Yeditepe University, Istanbul, Turkey; Department of Molecular Biology and Genetics, Faculty of Engineering and Natural Sciences, Istanbul Sabahattin Zaim University, Istanbul, Turkey.
Eur J Pharmacol. 2020 Sep 15;883:173342. doi: 10.1016/j.ejphar.2020.173342. Epub 2020 Jul 4.
Parkinson's disease (PD) is the second most prevalent neurodegenerative disease, and oxidative stress and mitochondrial dysfunction play a major role in the pathogenesis of PD. Since conventional therapeutics are not sufficient for the treatment of PD, the development of new agents with anti-oxidant potential is crucial. Caffeic Acid Phenethyl Ester (CAPE), a biologically active flavonoid of propolis, possesses several biological properties such as immunomodulatory, anti-inflammatory and anti-oxidative. In the present study, we investigated the neuroprotective effects of CAPE against 6-hydroxydopamine (6-OHDA)-induced SH-SY5Y cells. The neuroprotective effects were detected by using cell viability, Annexin V, Hoechst staining, total caspase activity, cell cycle, as well as western blotting. Besides, the anti-oxidative activity was measured by the production of reactive oxygen species and mitochondrial function was determined by measurement of mitochondrial membrane potential (ΔΨm). We found that CAPE significantly increased cell viability and decreased apoptotic cell death (20%) after 150 μM 6-OHDA exposure following 24 h. 1.25 μM CAPE also prevented 6-OHDA-induced changes in condensed nuclear morphology. Furthermore, treatment with 1.25 μM CAPE increased mitochondrial membrane potential in 6-OHDA-exposed cells. CAPE inhibited 6-OHDA-induced caspase activity (2 fold) and production of reactive oxygen species. In addition, 150 μM 6-OHDA-induced down-regulation of Bcl-2 and Akt levels and up-regulation of Bax and cleaved caspase-9/caspase-9 levels were partially restored by 1.25 μM CAPE treatment. These results revealed a neuroprotective potential of CAPE against 6-OHDA-induced apoptosis in an in vitro PD model and may be a potential therapeutic candidate for the prevention of neurodegeneration in Parkinson's Disease.
帕金森病（PD）是第二大常见的神经退行性疾病，氧化应激和线粒体功能障碍在 PD 的发病机制中起主要作用。由于传统的治疗方法不足以治疗 PD，因此开发具有抗氧化潜力的新药物至关重要。咖啡酸苯乙酯（CAPE）是蜂胶中的一种生物活性类黄酮，具有免疫调节、抗炎和抗氧化等多种生物学特性。在本研究中，我们研究了 CAPE 对 6-羟多巴胺（6-OHDA）诱导的 SH-SY5Y 细胞的神经保护作用。通过细胞活力、Annexin V、Hoechst 染色、总半胱天冬酶活性、细胞周期以及 Western blot 检测来检测神经保护作用。此外，通过活性氧的产生来测量抗氧化活性，并通过测量线粒体膜电位（ΔΨm）来确定线粒体功能。我们发现，在 6-OHDA 暴露 24 小时后，150 μM 6-OHDA 暴露后，CAPE 可显著增加细胞活力并降低凋亡细胞死亡（约 20%）。1.25 μM CAPE 还可防止 6-OHDA 诱导的核形态凝聚变化。此外，用 1.25 μM CAPE 处理可增加 6-OHDA 暴露细胞中的线粒体膜电位。CAPE 抑制 6-OHDA 诱导的半胱天冬酶活性（~2 倍）和活性氧的产生。此外，150 μM 6-OHDA 诱导的 Bcl-2 和 Akt 水平下调以及 Bax 和 cleaved caspase-9/caspase-9 水平上调，被 1.25 μM CAPE 处理部分恢复。这些结果揭示了 CAPE 在体外 PD 模型中对 6-OHDA 诱导的细胞凋亡的神经保护潜力，可能是预防帕金森病神经退行性变的潜在治疗候选药物。
