ABSTRACT
Alpha-lipoic acid (LA) is a powerful antioxidant. LA has two enantiomers, R(+)-LA (R-LA) and S(-)-LA (S-LA). Of these, R-LA is naturally occurring and an essential cofactor in energy metabolism. R-LA treatment has been reported to affect glucose metabolism in rat hepatoma cells. This study analyzed the time course of metabolite levels in LA-treated cultured H4IIEC3 rat hepatoma cells, including a specific evaluation of the effect of R-LA and the enantioselectivity of LA. Principal component analysis showed that this experiment was well designed to observe enantioselectivity. R-LA treatment was found to inhibit the glycolysis and Thr-Gly-Ser pathways, as well as lactic acid production, leading to the inhibition of gluconeogenesis in starved H4IIEC3 cells. This study may provide mechanistic insight into how R-LA induces apoptosis in hepatoma cells.
Subject(s)
Carcinoma, Hepatocellular/metabolism , Liver Neoplasms/metabolism , Thioctic Acid/pharmacology , Apoptosis/drug effects , Carcinoma, Hepatocellular/genetics , Cell Line, Tumor , Cells, Cultured , Glucose/metabolism , Humans , Liver Neoplasms/genetics , Metabolomics , Reactive Oxygen Species/metabolism , Stereoisomerism , Thioctic Acid/chemistryABSTRACT
Dietary stilbenoids are receiving increasing attention due to their potential health benefits. However, most studies concerning the bioactivity of stilbenoids were conducted with pure compounds, for example, resveratrol. The aim of this study was to characterize a complex root extract of Vitis vinifera in terms of its free radical scavenging and cellular antioxidant and anti-inflammatory properties. HPLC-ESI-MS/MS analyses of the root extract of Vitis vinifera identified seven stilbenoids including two monomeric (resveratrol and piceatannol), two dimeric (trans-É-viniferin and ampelopsin A), one trimeric (miyabenol C), and two tetrameric (r-2-viniferin = vitisin A and r-viniferin = vitisin B) compounds which may mediate its biological activity. Electron spin resonance and spin trapping experiments indicate that the root extract scavenged 2,2-diphenyl-1-picrylhydrazyl, hydroxyl, galvinoxyl, and superoxide free radicals. On a cellular level it was observed that the root extract of Vitis vinifera protects against hydrogen peroxide-induced DNA damage and induces Nrf2 and its target genes heme oxygenase-1 and γ-glutamylcysteine synthetase. Furthermore, the root extract could induce the antiatherogenic hepatic enzyme paraoxonase 1 and downregulate proinflammatory gene expression (interleukin 1ß, inducible nitric oxide synthase) in macrophages. Collectively our data suggest that the root extract of Vitis vinifera exhibits free radical scavenging as well as cellular antioxidant and anti-inflammatory properties.
