title: Gamma-decanolactone inhibits iNOS and TNF-alpha production by lipopolysaccharide-activated microglia in N9 cells.
abstract: Activated microglia that produce reactive nitrogen species (RNS), inflammatory factors, reactive oxygen species (ROS), and other neurovirulent factors may lead to the development of neurodegenerative diseases. Certain compounds can inhibit the activation of microglia. However, these mechanisms remain unclear. In the present study, we investigated the inhibitory effect of Gamma-decanolactone (GD) on the production of reactive oxygen species and inducible nitric oxide synthase (iNOS) in lipopolysaccharide (LPS) - stimulated N9 murine microglial cells through the p38 MAPK signaling pathway. The results showed that GD attenuated the activation of N9 cells and inhibited intracellular reactive oxygen species and the expression of iNOS and TNF-α induced by LPS in the cells. In addition, GD blocked the phosphorylation of p38 and inhibited cleaved caspase-9 and DNA damage. These data indicate that GD has therapeutic potential for the treatment of neurodegenerative diseases, and that it exerts its effects by inhibiting inflammation.
authors.affiliation: Laboratory of Neuropharmacology and Toxicology Preclinical, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil.
authors.forename: Pricila
authors.initials: P
authors.lastname: Pflüger
authors.affiliation: Department of Basic Health Sciences - Laboratory of Genetic Toxicology - UFCSPA, Porto Alegre, RS, Brazil.
authors.forename: Cassiana Macagnan
authors.initials: CM
authors.lastname: Viau
authors.affiliation: Laboratory of Neuropharmacology and Toxicology Preclinical, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil.
authors.forename: Vanessa Rodrigues
authors.initials: VR
authors.lastname: Coelho
authors.affiliation: Department of Basic Health Sciences - Laboratory of Genetic Toxicology - UFCSPA, Porto Alegre, RS, Brazil.
authors.forename: Natália Alice
authors.initials: NA
authors.lastname: Berwig
authors.affiliation: Department of Basic Health Sciences - Laboratory of Genetic Toxicology - UFCSPA, Porto Alegre, RS, Brazil.
authors.forename: Renata Bartolomeu
authors.initials: RB
authors.lastname: Staub
authors.affiliation: Laboratory of Neuropharmacology and Toxicology Preclinical, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil.
authors.forename: Patrícia
authors.initials: P
authors.lastname: Pereira
authors.affiliation: Department of Basic Health Sciences - Laboratory of Genetic Toxicology - UFCSPA, Porto Alegre, RS, Brazil. Electronic address: jenifers@ufcspa.edu.br.
authors.forename: Jenifer
authors.initials: J
authors.lastname: Saffi
mesh_terms: D000818:Animals; D053453:Caspase 9 / Q000378:metabolism; D002460:Cell Line; D053960:DNA Breaks / Q000187:drug effects; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D007783:Lactones / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D051379:Mice; D017628:Microglia / Q000187:drug effects* / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis*; D010766:Phosphorylation / Q000187:drug effects; D059748:Proteolysis / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D007783:Lactones; D008070:Lipopolysaccharides; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; C109757:decan-4-olide; D052247:Nitric Oxide Synthase Type II; D048051:p38 Mitogen-Activated Protein Kinases; D053453:Caspase 9
keywords: Cleaved caspase-9; DNA damage; Epilepsy; Gamma-decanolactone (GD); NOS; Reactive oxygen species