RESUMO
Recent evidence shows that rooibos compounds, aspalathin and phenylpyruvic acid-2-O-ß-D-glucoside (PPAG), can independently protect cardiomyocytes from hyperglycemia-related reactive oxygen species (ROS). While aspalathin shows more potency by enhancing intracellular antioxidant defenses, PPAG acts more as an anti-apoptotic agent. Thus, to further understand the protective capabilities of these compounds against hyperglycemia-induced cardiac damage, their combinatory effect was investigated and compared to metformin. An in vitro model of H9c2 cardiomyocytes exposed to chronic glucose concentrations was employed to study the impact of such compounds on hyperglycemia-induced damage. Here, high glucose exposure impaired myocardial substrate utilization by abnormally enhancing free fatty acid oxidation while concomitantly suppressing glucose oxidation. This was paralleled by altered expression of genes involved in energy metabolism including acetyl-CoA carboxylase (ACC), 5' AMP-activated protein kinase (AMPK), and peroxisome proliferator-activated receptor-alpha (PPARα). The combination treatment improved myocardial substrate metabolism, maintained mitochondrial membrane potential, and attenuated various markers for oxidative stress including nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity and glutathione content. It also showed a much-improved effect by ameliorating DNA damage when compared to metformin. The current study demonstrates that rooibos compounds offer unique cardioprotective properties against hyperglycemia-induced and potentially against diabetes-induced cardiac damage. These data also support further exploration of rooibos compounds to better assess the cardioprotective effects of different bioactive compound combinations.
Assuntos
Aspalathus/química , Chalconas/farmacologia , Dano ao DNA/efeitos dos fármacos , Glucose/efeitos adversos , Glucosídeos/farmacologia , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Ácidos Fenilpirúvicos/farmacologia , Quinases Proteína-Quinases Ativadas por AMP , Animais , Células Cultivadas , Chalconas/isolamento & purificação , Metabolismo Energético/efeitos dos fármacos , Metabolismo Energético/genética , Expressão Gênica/efeitos dos fármacos , Glucosídeos/isolamento & purificação , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Metformina/farmacologia , Miócitos Cardíacos/patologia , NADPH Oxidases/metabolismo , PPAR alfa/metabolismo , Ácidos Fenilpirúvicos/isolamento & purificação , Proteínas Quinases/metabolismo , Ratos , Espécies Reativas de Oxigênio/metabolismoRESUMO
Solanaceous medicinal plants produce tropane alkaloids (TAs). We discovered a novel gene from Atropa belladonna, AbPPAR, which encodes a phenylpyruvic acid reductase required for TA biosynthesis. AbPPAR was specifically expressed in root pericycles and endodermis. AbPPAR was shown to catalyze reduction of phenylpyruvic acid to phenyllactic acid, a precursor of TAs. Suppression of AbPPAR disrupted TA biosynthesis through reduction of phenyllactic acid levels. In summary, we identified a novel enzyme involved in TA biosynthesis.
Assuntos
Alcaloides/biossíntese , Oxirredutases/metabolismo , Ácidos Fenilpirúvicos/metabolismo , Tropanos/metabolismo , Alcaloides/química , Atropa belladonna/química , Atropa belladonna/metabolismo , Estrutura Molecular , Oxirredutases/química , Oxirredutases/isolamento & purificação , Ácidos Fenilpirúvicos/química , Ácidos Fenilpirúvicos/isolamento & purificação , Tropanos/químicaRESUMO
Xenofuranones A (1) and B (2) have been isolated from cultures of the insect-pathogenic bacterium Xenorhabdus szentirmaii, and their structures were elucidated by NMR and mass spectroscopy. Both compounds show similarities to fungal furanones, and their biosynthesis was studied using a reversed approach by feeding putative 12C precursors to an overall 13C background in small-scale experiments followed by gas chromatographic analysis coupled to mass spectrometry.
Assuntos
Furanos/isolamento & purificação , Ácidos Fenilpirúvicos/isolamento & purificação , Xenorhabdus/química , Animais , Comportamento Alimentar/efeitos dos fármacos , Furanos/química , Furanos/farmacologia , Insetos/efeitos dos fármacos , Camundongos , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Ácidos Fenilpirúvicos/química , Ácidos Fenilpirúvicos/farmacologia , Xenorhabdus/patogenicidadeRESUMO
Investigation of a Philippine specimen of the red alga Ceratodictyon spongiosum and its sponge symbiont Haliclona cymaeformis led to the isolation of p-sulfooxyphenylpyruvic acid, whose structure was elucidated using spectroscopic methods, with the Z-enol geometry determined through analysis of (3)J(C,H) coupling constants. The metabolite was tested for tyrosine kinase inhibition using a (3)H-thymidine incorporation assay, but was found inactive.