Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China; Post-doctoral Scientific Research Center, China Academy of Chinese Medical Sciences, Beijing 100700, China.
Institute of Medicinal Plant Development (IMPLAD), Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100193, China.
Phytomedicine. 2019 Feb;53:193-204. doi: 10.1016/j.phymed.2018.09.005. Epub 2018 Sep 6.
Flavanomarein is the main component of Coreopsis tinctoria Nutt. (C. tinctoria), which is a globally well-known flower tea that has a distinct flavor and many beneficial health effects, such as antioxidant activities. We aimed to explore the effect of flavanomarein on a 6-hydroxydopamine (6-OHDA)-lesioned cell model of oxidative stress.
In this study, we used 6-OHDA-lesioned PC12 cells and primary cortical neurons to investigate the protective effects of flavanomarein and its potential mechanism.
The results indicated that pretreatment with flavanomarein (25, 50, or 100 µM for 24 h) significantly increased the cell viability, reduced the lactate dehydrogenase (LDH) release and improved the mitochondrial membrane potential (∆Ψm) and mitochondrial impairment. Additionally, flavanomarein markedly reduced the gene expression of tumor necrosis factor (TNF)-α and protein kinase C ζ (PKC-ζ), the nuclear translocation of p65, and the levels of p-AMPK-α and acetyl-p53. Flavanomarein also elevated the gene expression of P85α, PKC-β1, and Bcl-2, the protein expression of Sirt1 and ICAD, and the phosphorylation level of AKT.
Together, these results suggest that flavanomarein protects PC12 cells and primary cortical neurons from 6-OHDA-induced neurotoxicity by upregulating the PI3K/AKT signaling pathway and attenuating the nuclear factor kappa B (NF-κB) signaling pathway. Therefore, our study provides evidence that may aid in the development of a potential compound against 6-OHDA toxicity.
黄烷马雷因是金鸡菊（Coreopsis tinctoria Nutt.）的主要成分，金鸡菊是一种全球知名的花茶，具有独特的风味和许多有益的健康功效，如抗氧化活性。我们旨在探索黄烷马雷因对氧化应激的 6-羟多巴胺（6-OHDA）损伤细胞模型的影响。
在这项研究中，我们使用 6-OHDA 损伤的 PC12 细胞和原代皮质神经元来研究黄烷马雷因的保护作用及其潜在机制。
结果表明，黄烷马雷因（25、50 或 100µM，预处理 24 小时）显著增加细胞活力，降低乳酸脱氢酶（LDH）释放，并改善线粒体膜电位（∆Ψm）和线粒体损伤。此外，黄烷马雷因显著降低肿瘤坏死因子（TNF）-α和蛋白激酶 C ζ（PKC-ζ）的基因表达、p65 的核转位以及 p-AMPK-α和乙酰化-p53 的水平。黄烷马雷因还增加了 P85α、PKC-β1 和 Bcl-2 的基因表达、Sirt1 和 ICAD 的蛋白表达以及 AKT 的磷酸化水平。
综上所述，这些结果表明，黄烷马雷因通过上调 PI3K/AKT 信号通路和抑制核因子 kappa B（NF-κB）信号通路来保护 PC12 细胞和原代皮质神经元免受 6-OHDA 诱导的神经毒性。因此，我们的研究为开发潜在的抗 6-OHDA 毒性化合物提供了证据。
