Structure fingerprint generation through cylinder model

ator of transition metals. While many studies have focused on the organosulfur compounds in AGE, including S-allyl-L-cysteine, allicin and allyl thiosulfinates, less attention has been paid to the carbohydrate derivatives, such as N-a–L-arginine, as bioactive components. FruArg belongs to the class of fructosamines, which originate from a nonenzymatic reaction between glucose and arginine; they modify proteins in vivo and are widely used as a diagnostic marker of long-term glucose concentration in diabetics. Fructosamine derivatives are formed in foods upon storage or dehydration and are regarded as a functional food. There is evidence that fructose-amino acids can act as immune-stimulants and inhibit tumorigenesis and metastasis in animal models of cancer. FruArg was initially extracted from Korean red ginseng as a novel substrate of nitric oxide synthase. It has been also identified as a major component in AGE and is generally present at 22.5 mM concentration. FruArg exhibits antioxidant properties PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/19682342 and is capable of scavenging hydrogen peroxide and protecting macrophages or endothelial cells from the damaging effects of oxidized low-density lipoprotein. In vivo, FruArg was shown to suppress noradrenalin-induced hypertension and reduce postprandial blood glucose level. These findings suggest that AGE and FruArg may offer beneficial effects by reduction of chronic innate immune activation. As a part of our longstanding interest in dietary antioxidants in promotion of resilience in brain health, an important goal for this study is to investigate the protective effects of AGE and FruArg in neuroinflammation and elucidate their mode of action in microglial cells. 2 / 25 Effects of Garlic Extract on LPS-Stimulated Microglia Microglia are the resident immune effector cells in the central nervous system with the ability to confer resilience against oxidative and inflammatory responses by increasing production of the anti-oxidative products in responding to various types of injuries and environmental stress. Besides maintenance of immune response, microglial cells can be activated upon phagocytosis of invading bacteria or endocytosis of toxins and produce reactive oxygen/nitrogen species including nitric oxide. Excessive production of NO can induce nitrosative PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/19682532 stress in the cell and contributes to neurovascular injuries leading to neurodegenerative diseases including traumatic brain injury, cerebral ischemia, Parkinson’s disease and Alzheimer’s disease. Therefore, agents that can attenuate microglial activation, suppress chronic production of proinflammatory molecules, and/or increase production of antioxidants in the brain are of interest for the development of novel approaches in prevention of neurodegenerative diseases. In the present study, we assessed effects of AGE and FruArg in lipopolysaccharide -activated murine BV-2 microglial cells, a well-defined paradigm for study of neuroinflammatory responses. Quantitative proteomic analyses by two dimensional differential in-gel electrophoresis combined with liquid chromatography tandem mass spectrometry identified multiple molecular targets of AGE and FruArg in LPS-stimulated BV-2 cells. Using Ingenuity Pathway HC-067047 analysis and MULTICOM-PDCN analysis, we predicted signal transduction pathways and protein networks that are modulated by AGE and FruArg, thus providing important insights into the molecular mechanisms that may underlie their beneficial effects in brain health and promotion of resilien

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