title: Effects of aged garlic extract and FruArg on gene expression and signaling pathways in lipopolysaccharide-activated microglial cells.
abstract: Aged garlic extract (AGE) is widely used as a dietary supplement on account of its protective effects against oxidative stress and inflammation. But less is known about specific molecular targets of AGE and its bioactive components, including N-α-(1-deoxy-D-fructos-1-yl)-L-arginine (FruArg). Our recent study showed that both AGE and FruArg significantly attenuate lipopolysaccharide (LPS)-induced neuroinflammatory responses in BV-2 microglial cells. This study aims to unveil effects of AGE and FruArg on gene expression regulation in LPS stimulated BV-2 cells. Results showed that LPS treatment significantly altered mRNA levels from 2563 genes. AGE reversed 67% of the transcriptome alteration induced by LPS, whereas FruArg accounted for the protective effect by reversing expression levels of 55% of genes altered by LPS. Key pro-inflammatory canonical pathways induced by the LPS stimulation included toll-like receptor signaling, IL-6 signaling, and Nrf2-mediated oxidative stress pathway, along with elevated expression levels of genes, such as Il6, Cd14, Casp3, Nfkb1, Hmox1, and Tnf. These effects could be modulated by treatment with both AGE and FruArg. These findings suggests that AGE and FruArg are capable of alleviating oxidative stress and neuroinflammatory responses stimulated by LPS in BV-2 cells.
authors.affiliation: Department of Pathology &Anatomical Sciences, University of Missouri School of Medicine, Columbia, MO 65212, USA.|Center for Translational Neuroscience, University of Missouri School of Medicine, Columbia, MO 65212, USA.|Center for Botanical Interaction Studies, University of Missouri, Columbia, MO 65211, USA.
authors.forename: Hailong
authors.initials: H
authors.lastname: Song
authors.affiliation: Department of Biochemistry, University of Missouri, Columbia, MO 65211, USA.|Xiphophorus Genetic Stock Center, Texas State University, San Marcos, TX 78666, USA.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Department of Pathology &Anatomical Sciences, University of Missouri School of Medicine, Columbia, MO 65212, USA.|Center for Translational Neuroscience, University of Missouri School of Medicine, Columbia, MO 65212, USA.|Center for Botanical Interaction Studies, University of Missouri, Columbia, MO 65211, USA.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Qu
authors.affiliation: Department of Biochemistry, University of Missouri, Columbia, MO 65211, USA.
authors.forename: Valeri V
authors.initials: VV
authors.lastname: Mossine
authors.affiliation: Department of Biochemistry, University of Missouri, Columbia, MO 65211, USA.
authors.forename: Matthew B
authors.initials: MB
authors.lastname: Martin
authors.affiliation: Center for Botanical Interaction Studies, University of Missouri, Columbia, MO 65211, USA.|Department of Computer Science, Informatics Institute, University of Missouri, Columbia, MO 65211, USA.
authors.forename: Jie
authors.initials: J
authors.lastname: Hou
authors.affiliation: Department of Pathology &Anatomical Sciences, University of Missouri School of Medicine, Columbia, MO 65212, USA.|Center for Translational Neuroscience, University of Missouri School of Medicine, Columbia, MO 65212, USA.|Center for Botanical Interaction Studies, University of Missouri, Columbia, MO 65211, USA.
authors.forename: Jiankun
authors.initials: J
authors.lastname: Cui
authors.affiliation: Department of Biochemistry, University of Missouri, Columbia, MO 65211, USA.
authors.forename: Brenda A
authors.initials: BA
authors.lastname: Peculis
authors.affiliation: Department of Biochemistry, University of Missouri, Columbia, MO 65211, USA.
authors.forename: Thomas P
authors.initials: TP
authors.lastname: Mawhinney
authors.affiliation: Center for Botanical Interaction Studies, University of Missouri, Columbia, MO 65211, USA.|Department of Computer Science, Informatics Institute, University of Missouri, Columbia, MO 65211, USA.
authors.forename: Jianlin
authors.initials: J
authors.lastname: Cheng
authors.affiliation: Center for Botanical Interaction Studies, University of Missouri, Columbia, MO 65211, USA.|Department of Chemistry, University of Missouri, Columbia, MO 65211, USA.
authors.forename: C Michael
authors.initials: CM
authors.lastname: Greenlief
authors.affiliation: Center for Botanical Interaction Studies, University of Missouri, Columbia, MO 65211, USA.|Divison of Animal Sciences, University of Missouri, Columbia, MO 65211, USA.
authors.forename: Kevin
authors.initials: K
authors.lastname: Fritsche
authors.affiliation: Department of Biochemistry, University of Missouri, Columbia, MO 65211, USA.
authors.forename: Francis J
authors.initials: FJ
authors.lastname: Schmidt
authors.affiliation: Xiphophorus Genetic Stock Center, Texas State University, San Marcos, TX 78666, USA.
authors.forename: Ronald B
authors.initials: RB
authors.lastname: Walter
authors.affiliation: Center for Botanical Interaction Studies, University of Missouri, Columbia, MO 65211, USA.|Department of Biochemistry, University of Missouri, Columbia, MO 65211, USA.
authors.forename: Dennis B
authors.initials: DB
authors.lastname: Lubahn
authors.affiliation: Department of Pathology &Anatomical Sciences, University of Missouri School of Medicine, Columbia, MO 65212, USA.|Center for Translational Neuroscience, University of Missouri School of Medicine, Columbia, MO 65212, USA.|Center for Botanical Interaction Studies, University of Missouri, Columbia, MO 65211, USA.|Department of Biochemistry, University of Missouri, Columbia, MO 65211, USA.
authors.forename: Grace Y
authors.initials: GY
authors.lastname: Sun
authors.affiliation: Department of Pathology &Anatomical Sciences, University of Missouri School of Medicine, Columbia, MO 65212, USA.|Center for Translational Neuroscience, University of Missouri School of Medicine, Columbia, MO 65212, USA.|Center for Botanical Interaction Studies, University of Missouri, Columbia, MO 65211, USA.
authors.forename: Zezong
authors.initials: Z
authors.lastname: Gu
mesh_terms: D000975:Antioxidants / Q000378:metabolism; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D005632:Fructose / Q000031:analogs & derivatives* / Q000494:pharmacology*; D005737:Garlic / Q000737:chemistry*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D007249:Inflammation; D015850:Interleukin-6 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008264:Macrophages / Q000378:metabolism; D017628:Microglia / Q000187:drug effects* / Q000378:metabolism; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D018384:Oxidative Stress; D010936:Plant Extracts / Q000494:pharmacology*; D025341:Principal Component Analysis; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction; D059467:Transcriptome
chemical_list: D000975:Antioxidants; C508600:IL6 protein, human; D015850:Interleukin-6; D008070:Lipopolysaccharides; D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; D010936:Plant Extracts; D012333:RNA, Messenger; D005632:Fructose; D001120:Arginine