α- and β-Naphthoflavone synergistically attenuate H2O2-induced neuron SH-SY5Y cell damage

Exp Ther Med. 2017 Mar;13(3):1143-1150. doi: 10.3892/etm.2017.4045. Epub 2017 Jan 13.

Abstract

Previous studies have demonstrated an association between neurological diseases and oxidative stress (OS). Naphthoflavone is a synthetic derivative of naturally occurring flavonoids that serves an important role in the treatment and prevention of OS-related diseases. The current study was designed to apply α- and β-Naphthoflavone individually and in combination to counteract the detrimental effects of OS on neurons in vitro. Neuronal SH-SY5Y cells were subjected to 20 µM H2O2, followed by exposure to 20 µM α-Naphthoflavone and/or 10 µM β-Naphthoflavone. Results indicated that α- and β-Naphthoflavone effectively antagonized the apoptosis-promoting effect of H2O2 on neuronal SH-SY5Y cells, and that β-Naphthoflavone significantly (P<0.05) reversed H2O2-inhibited cell viability. Notably, co-treatment of α- and β-Naphthoflavone reversed the H2O2-induced apoptosis rate elevation and cell viability reduction. Further analysis demonstrated that H2O2 inhibited the activities of antioxidant enzymes including catalase, superoxide dismutase and glutathione peroxidase, but this was reversed by the co-treatment with α- and β-Naphthoflavone and selectively enhanced by the treatment with α- or β-Naphthoflavone. H2O2-stimulated p38 mitogen-activated protein kinase activation was repressed following treatment with α- and/or β-Naphthoflavone, along with a decreased expression of the apoptosis-related factors and inhibited caspase-3 activation. In conclusion, co-treatment with α- and β-Naphthoflavone minimized H2O2-led neuron damage compared with treatment with α- or β-Naphthoflavone, suggesting a synergetic effect between α- and β-Naphthoflavone. This indicates that utilizing α- and β-Naphthoflavone together in the clinical setting may provide a novel therapeutic for neurological disease.

Keywords: antioxidant enzyme activity; oxidative stress; p38 mitogen-activated protein kinase; α-Naphthoflavone; β-Naphthoflavone.