Neuroprotective Effects of SG-168 Against Oxidative Stress-Induced Apoptosis in PC12 Cells

Abstract

Postmortem examinations of tissues of humans and rodents with a host of neurodegenerative conditions, including Alzheimer's and Parkinson's diseases, have identified oxidative damage in proteins, lipids, and DNA. The aim of this study was to better understand the cellular mechanisms of neuronal cell degeneration induced via oxidative stress and the protective roles of bioactive substance. In order to achieve this aim, we established a screening program to discover therapeutic agents that exhibit preferential neuroprotective activity in H₂O₂-treated PC12 cells. During the course of our screening program, we isolated an active compound, SG-168, from Dendrobium nobile Lindley and identified it as a neuroprotective agent. SG-168 was identified as a compound with an acetal skeleton, a prototypical compound, by electrospray ionization-mass spectrometry analysis and various nuclear magnetic resonance spectroscopic methods. The protective effect of SG-168 in PC12 cells with H₂O₂-induced oxidative damage was investigated by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide reduction assay. As expected, incubation with H₂O₂ for 2 hours resulted in cell viability of 31.8% compared to the control, while pretreatment of SG-168 increased cell viability by 15–50% compared to the H₂O₂-stressed control cells. These results showed that SG-168 inhibits H₂O₂-induced apoptotic cell death. Interestingly, flow cytometric analysis showed that H₂O₂-treated PC12 cells incubated with SG-168 exhibited greatly suppressed apoptosis. In summation, the results of this study suggest that SG-168 has potential as a new antioxidant agent against neuronal diseases.