title: Anti-inflammatory effects and antioxidant activity of dihydroasparagusic acid in lipopolysaccharide-activated microglial cells.
abstract: The activation of microglia and subsequent release of toxic pro-inflammatory factors are crucially associated with neurodegenerative disease, characterized by increased oxidative stress and neuroinflammation, including Alzheimer and Parkinson diseases and multiple sclerosis. Dihydroasparagusic acid is the reduced form of asparagusic acid, a sulfur-containing flavor component produced by Asparagus plants. It has two thiolic functions able to coordinate the metal ions, and a carboxylic moiety, a polar function, which may enhance excretion of the complexes. Thiol functions are also present in several biomolecules with important physiological antioxidant role as glutathione. The aim of this study is to evaluate the anti-inflammatory and antioxidant potential effect of dihydroasparagusic acid on microglial activation in an in vitro model of neuroinflammation. We have used lipopolysaccharide to induce an inflammatory response in primary rat microglial cultures. Our results suggest that dihydroasparagusic acid significantly prevented lipopolysaccharide-induced production of pro-inflammatory and neurotoxic mediators such as nitric oxide, tumor necrosis factor-α, prostaglandin E2, as well as inducible nitric oxide synthase and cyclooxygenase-2 protein expression and lipoxygenase activity in microglia cells. Moreover it effectively suppressed the level of reactive oxygen species and affected lipopolysaccharide-stimulated activation of mitogen activated protein kinase, including p38, and nuclear factor-kB pathway. These results suggest that dihydroasparagusic acid's neuroprotective properties may be due to its ability to dampen induction of microglial activation. It is a compound that can effectively inhibit inflammatory and oxidative processes that are important factors of the etiopathogenesis of neurodegenerative diseases.
authors.affiliation: Department of Physiology and Pharmacology "Vittorio Erspamer", Sapienza University of Rome, P.le A. Moro 5, 00185 Rome, Italy. Electronic address: adele.salemme@uniroma1.it.
authors.forename: Adele
authors.initials: A
authors.lastname: Salemme
authors.affiliation: Department of Physiology and Pharmacology "Vittorio Erspamer", Sapienza University of Rome, P.le A. Moro 5, 00185 Rome, Italy.
authors.forename: Anna Rita
authors.initials: AR
authors.lastname: Togna
authors.affiliation: Laboratory of Cutaneous Physiopathology and Integrated Center of Metabolomics Research, San Gallicano Dermatologic Institute (IRCCS), via Elio Chianesi 53, 00144 Rome, Italy.
authors.forename: Arianna
authors.initials: A
authors.lastname: Mastrofrancesco
authors.affiliation: Department of Physiology and Pharmacology "Vittorio Erspamer", Sapienza University of Rome, P.le A. Moro 5, 00185 Rome, Italy.
authors.forename: Vittoria
authors.initials: V
authors.lastname: Cammisotto
authors.affiliation: Laboratory of Cutaneous Physiopathology and Integrated Center of Metabolomics Research, San Gallicano Dermatologic Institute (IRCCS), via Elio Chianesi 53, 00144 Rome, Italy.
authors.forename: Monica
authors.initials: M
authors.lastname: Ottaviani
authors.affiliation: Department of Chemistry, Sapienza University of Rome, P.le A. Moro 5, 00185 Rome, Italy.
authors.forename: Armandodoriano
authors.initials: A
authors.lastname: Bianco
authors.affiliation: Department of Chemistry, Sapienza University of Rome, P.le A. Moro 5, 00185 Rome, Italy; Department of Environmental Biology, Sapienza University of Rome, P.le A. Moro 5, 00185 Rome, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Venditti
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000187:drug effects / Q000276:immunology; D004353:Drug Evaluation, Preclinical; D007249:Inflammation / Q000188:drug therapy* / Q000378:metabolism; D008070:Lipopolysaccharides; D017628:Microglia / Q000187:drug effects* / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D015213:Neuroimmunomodulation / Q000187:drug effects / Q000502:physiology; D009569:Nitric Oxide / Q000378:metabolism; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D013876:Thiophenes / Q000494:pharmacology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D008070:Lipopolysaccharides; D016328:NF-kappa B; D017382:Reactive Oxygen Species; D013876:Thiophenes; C585333:dihydroasparagusic acid; D009569:Nitric Oxide; D048051:p38 Mitogen-Activated Protein Kinases
keywords: Dihydroasparagusic acid; Inflammation; Lipopolysaccharide; Microglia; Neurodegenerative disease; Oxidative stress