ABSTRACT
The effects of ginseng oligosaccharides (GSOs) on neuronal oxidative injury induced by glutamate (GLU) and the molecular mechanisms involved were investigated. Cell damage was assessed using MTT assays, and the lactate dehydrogenase (LDH) release rate and flow cytometry were used to detect the accumulation of reactive oxygen species (ROS) and mitochondrial membrane potential respectively. The levels of catalase (CAT) and glutathione (GSH) were measured in PC12 cells and Drosophila brain tissue. The climbing ability of Drosophila was observed. Levels of proteins, including Cyt C, Bcl-2/BAX, and Nrf2/HO-1-associated proteins, were determined by western blotting and immunofluorescence. It was found that GSOs reversed GLU-induced reductions in cell viability and the LDH release rate, and rescued ROS accumulation. GSOs also mitigated the deleterious effects of GLU on the mitochondrial membrane potential and Cyt C release, thus alleviating mitochondrial dysfunction, and increased GSH levels and CAT activity in both cells and Drosophila brain tissue. The climbing index in GSO-treated Drosophila was significantly higher than that in the tert-butyl-hydroperoxide-treated flies. Furthermore, GSOs protected cells against GLU-induced apoptosis by reducing the expression of the mitochondrial apoptosis-associated Bcl-2 family effector proteins and protected cells from GLU-induced oxidative damage by increasing the nuclear translocation of Nrf2 and HO-1 expression. These findings indicate that GSOs protect against GLU-induced neuronal oxidative damage through Nrf2/HO-1 activation.
Subject(s)
NF-E2-Related Factor 2 , Panax , Animals , Apoptosis , Drosophila/metabolism , Glutamic Acid/metabolism , Glutathione/metabolism , Heme Oxygenase-1/genetics , Heme Oxygenase-1/metabolism , NF-E2-Related Factor 2/genetics , NF-E2-Related Factor 2/metabolism , Neurons/metabolism , Oligosaccharides/pharmacology , Oxidative Stress , Panax/metabolism , Proto-Oncogene Proteins c-bcl-2/metabolism , Rats , Reactive Oxygen Species/metabolism , Signal TransductionABSTRACT
Elevated free fatty acids may impair insulin-mediated signaling to eNOS that contributes to the pathophysiology of endothelial dysfunction. Previous studies have indicated the protective effect of ginseng and the regulatory potential of phenolic acid components from other plants on endothelial function. Therefore, this study investigated the protective effects of phenolic acid extract from ginseng (PG2) on endothelial cells against palmitate-induced damage. We found that PG2 increases cell viability, inhibits the palmitate-induced intracellular accumulation of lipids, and the overexpression of endothelin-1 (ET-1) through enhancing the phosphorylation of the phosphatidylinositol 3-kinase/Akt/endothelial nitric oxide synthase (PI3K/Akt/eNOS) signaling pathway. The results of this study may be valuable for the development of PG2 to combat the endothelial cell damage caused by hyperlipidemia. PRACTICAL APPLICATION: We proved that phenolic acid extract from ginseng has a protective effect on free fatty acid-induced endothelial dysfunction in vitro. This study provides experimental data for the application of ginseng-derived phenolic acids in treating cardiovascular disease.