title: Proteomic analysis of the effects of aged garlic extract and its FruArg component on lipopolysaccharide-induced neuroinflammatory response in microglial cells.
abstract: Aged garlic extract (AGE) is widely used as a dietary supplement, and is claimed to promote human health through anti-oxidant/anti-inflammatory activities with hypolipidemic, antiplatelet and neuroprotective effects. Prior studies of AGE have mainly focused on its organosulfur compounds, with little attention paid to its carbohydrate derivatives, such as N-α-(1-deoxy-D-fructos-1-yl)-L-arginine (FruArg). The goal of this study is to investigate actions of AGE and FruArg on antioxidative and neuroinflammatory responses in lipopolysaccharide (LPS)-activated murine BV-2 microglial cells using a proteomic approach. Our data show that both AGE and FruArg can significantly inhibit LPS-induced nitric oxide (NO) production in BV-2 cells. Quantitative proteomic analysis by combining two dimensional differential in-gel electrophoresis (2D-DIGE) with mass spectrometry revealed that expressions of 26 proteins were significantly altered upon LPS exposure, while levels of 20 and 21 proteins exhibited significant changes in response to AGE and FruArg treatments, respectively, in LPS-stimulated BV-2 cells. Notably, approximate 78% of the proteins responding to AGE and FruArg treatments are in common, suggesting that FruArg is a major active component of AGE. MULTICOM-PDCN and Ingenuity Pathway Analyses indicate that the proteins differentially affected by treatment with AGE and FruArg are involved in inflammatory responses and the Nrf2-mediated oxidative stress response. Collectively, these results suggest that AGE and FruArg attenuate neuroinflammatory responses and promote resilience in LPS-activated BV-2 cells by suppressing NO production and by regulating expression of multiple protein targets associated with oxidative stress.
authors.affiliation: Department of Pathology and Anatomical Sciences, University of Missouri School of Medicine, Columbia, Missouri, United States of America; Center for Translational Neuroscience, University of Missouri School of Medicine, Columbia, Missouri, United States of America.
authors.forename: Hui
authors.initials: H
authors.lastname: Zhou
authors.affiliation: Department of Pathology and Anatomical Sciences, University of Missouri School of Medicine, Columbia, Missouri, United States of America; Center for Translational Neuroscience, University of Missouri School of Medicine, Columbia, Missouri, United States of America.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Qu
authors.affiliation: Department of Biochemistry, University of Missouri School of Medicine, Columbia, Missouri, United States of America.
authors.forename: Valeri V
authors.initials: VV
authors.lastname: Mossine
authors.affiliation: Department of Pathology and Anatomical Sciences, University of Missouri School of Medicine, Columbia, Missouri, United States of America; Center for Translational Neuroscience, University of Missouri School of Medicine, Columbia, Missouri, United States of America.
authors.forename: Dineo L
authors.initials: DL
authors.lastname: Nknolise
authors.affiliation: Department of Computer Science, Informatics Institute, University of Missouri, Columbia, Missouri, United States of America.
authors.forename: Jilong
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Pathology and Anatomical Sciences, University of Missouri School of Medicine, Columbia, Missouri, United States of America; Center for Translational Neuroscience, University of Missouri School of Medicine, Columbia, Missouri, United States of America.
authors.forename: Zhenzhou
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Department of Computer Science, Informatics Institute, University of Missouri, Columbia, Missouri, United States of America.
authors.forename: Jianlin
authors.initials: J
authors.lastname: Cheng
authors.affiliation: Department of Chemistry, University of Missouri, Columbia, Missouri, United States of America.
authors.forename: C Michael
authors.initials: CM
authors.lastname: Greenlief
authors.affiliation: Department of Biochemistry, University of Missouri School of Medicine, Columbia, Missouri, United States of America.
authors.forename: Thomas P
authors.initials: TP
authors.lastname: Mawhinney
authors.affiliation: British Columbia Institute of Technology, Vancouver, British Columbia, Canada.
authors.forename: Paula N
authors.initials: PN
authors.lastname: Brown
authors.affiliation: Division of Animal Sciences, University of Missouri, Columbia, Missouri, United States of America.
authors.forename: Kevin L
authors.initials: KL
authors.lastname: Fritsche
authors.affiliation: Department of Biochemistry, University of Missouri School of Medicine, Columbia, Missouri, United States of America.
authors.forename: Mark
authors.initials: M
authors.lastname: Hannink
authors.affiliation: Department of Biochemistry, University of Missouri School of Medicine, Columbia, Missouri, United States of America.
authors.forename: Dennis B
authors.initials: DB
authors.lastname: Lubahn
authors.affiliation: Department of Pathology and Anatomical Sciences, University of Missouri School of Medicine, Columbia, Missouri, United States of America; Department of Biochemistry, University of Missouri School of Medicine, Columbia, Missouri, United States of America; Center for Translational Neuroscience, University of Missouri School of Medicine, Columbia, Missouri, United States of America.
authors.forename: Grace Y
authors.initials: GY
authors.lastname: Sun
authors.affiliation: Department of Pathology and Anatomical Sciences, University of Missouri School of Medicine, Columbia, Missouri, United States of America; Center for Translational Neuroscience, University of Missouri School of Medicine, Columbia, Missouri, United States of America; Harry S. Truman Veterans Hospital, Columbia, Missouri, United States of America.
authors.forename: Zezong
authors.initials: Z
authors.lastname: Gu
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D015153:Blotting, Western; D002460:Cell Line; D004151:Dipeptides / Q000737:chemistry / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D015180:Electrophoresis, Gel, Two-Dimensional; D005737:Garlic / Q000737:chemistry*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D051379:Mice; D017628:Microglia / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D015394:Molecular Structure; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000378:metabolism; D010936:Plant Extracts / Q000494:pharmacology*; D020543:Proteome / Q000032:analysis*; D040901:Proteomics; D015398:Signal Transduction / Q000187:drug effects; D053719:Tandem Mass Spectrometry; D013997:Time Factors
chemical_list: D000893:Anti-Inflammatory Agents; D004151:Dipeptides; D008070:Lipopolysaccharides; D010936:Plant Extracts; D020543:Proteome; D009569:Nitric Oxide