The protective effects of the native flavanone flavanomarein on neuronal cells damaged by 6-OHDA

作者:Le Liang; Fu Hui; Lv Qiuyue; Bai Xue; Zhao Ying; Xiang Jiamei; Jiang Baoping*; Hu Keping; Chen Shilin*
来源:Phytomedicine, 2019, 53: 193-204.
DOI:10.1016/j.phymed.2018.09.005

摘要

Background: 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. Methods: 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. Results: The results indicated that pretreatment with flavanomarein (25, 50, or 100 mu M for 24 h) significantly increased the cell viability, reduced the lactate dehydrogenase (LDH) release and improved the mitochondrial membrane potential (Delta Psi m) and mitochondrial impairment. Additionally, flavanomarein markedly reduced the gene expression of tumor necrosis factor (TNF)-alpha and protein kinase C zeta (PKC-zeta), the nuclear translocation of p65, and the levels of p-AMPK-alpha and acetyl-p53. Flavanomarein also elevated the gene expression of P85 alpha, PKC-beta 1, and Bcl-2, the protein expression of Sirt1 and ICAD, and the phosphorylation level of AKT. Conclusions: 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-kappa B) signaling pathway. Therefore, our study provides evidence that may aid in the development of a potential compound against 6-OHDA toxicity.