title: Inhibitory effects and molecular mechanisms of garlic organosulfur compounds on the production of inflammatory mediators.
abstract: METHODS
  Garlic is used for both culinary and medicinal purposes by many cultures. The garlic organosulfur compounds (GOSCs) are thought to be bioactive components. This study aims to clarify the antiinflammatory effects and molecular mechanisms of GOSCs in both cell and animal models.
  
  
  RESULTS
  RAW264.7 cells were treated with six kinds of GOSCs to screen their influence on cyclooxygenase-2 and inducible nitric oxide synthase expression by Western blotting. Prostaglandin E2 and nitrite were measured by ELISA and Griess reaction, respectively. Cytokines in culture medium were assayed by the multiplex technology. Proteins were detected by Western blotting. Mouse paw edema was induced by LPS. The results revealed that diallyl trisulfide (DATS) was a strongest inhibitor for cyclooxygenase and inducible nitric oxide synthase among GOSCs, and reduced the levels of LPS-induced IL-6, IL-10, IL-12(p70), KC, MCP-1, and TNF-α. Cellular signaling analysis revealed that DATS downregulated AKT1/TGF-β-activated kinase-mediated mitogen-activated protein kinase (MAPK) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathways. Furthermore, DATS activated Nrf2-mediated expression of HO-1 and NQO1 and reduced LPS-induced intracellular reactive oxygen species, which may contribute to suppress inflammatory mediator production. Finally, in vivo data demonstrated that DATS attenuated LPS-induced mouse paw edema.
  
  
  CONCLUSIONS
  DATS as a potential inhibitor revealed antiinflammatory effect in both cell and animal models by downregulating AKT1/TGF-β-activated kinase-mediated NFκB and MAPK signaling pathways.
authors.affiliation: The Engineering Research Center of Feed Safety and Efficient Utilization of Education Ministry, Hunan Agriculture University, Changsha, Hunan, P. R. China; Department of Biochemical Science and Technology, Faculty of Agriculture, Kagoshima University, Korimoto, Kagoshima, Japan; College of Animal Medicine, Hunan Agriculture University, Changsha, Hunan, P. R. China.
authors.forename: Sixiang
authors.initials: S
authors.lastname: You
authors.forename: Eri
authors.initials: E
authors.lastname: Nakanishi
authors.forename: Hiroko
authors.initials: H
authors.lastname: Kuwata
authors.forename: Jihua
authors.initials: J
authors.lastname: Chen
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Nakasone
authors.forename: Xi
authors.initials: X
authors.lastname: He
authors.forename: Jianhua
authors.initials: J
authors.lastname: He
authors.forename: Xiangxin
authors.initials: X
authors.lastname: Liu
authors.forename: Shirui
authors.initials: S
authors.lastname: Zhang
authors.forename: Bin
authors.initials: B
authors.lastname: Zhang
authors.forename: De-Xing
authors.initials: DX
authors.lastname: Hou
mesh_terms: D000498:Allyl Compounds / Q000494:pharmacology*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D051546:Cyclooxygenase 2 / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D004195:Disease Models, Animal; D015536:Down-Regulation; D004487:Edema / Q000517:prevention & control; D005737:Garlic / Q000737:chemistry*; D051547:Heme Oxygenase-1 / Q000378:metabolism; D007249:Inflammation / Q000188:drug therapy; D016753:Interleukin-10 / Q000378:metabolism; D018664:Interleukin-12 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000009:adverse effects; D020930:MAP Kinase Kinase Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000378:metabolism; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D010766:Phosphorylation; D010936:Plant Extracts / Q000494:pharmacology*; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000378:metabolism; D017382:Reactive Oxygen Species; D015398:Signal Transduction / Q000187:drug effects; D013440:Sulfides / Q000494:pharmacology*; D016212:Transforming Growth Factor beta / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D000099151:MAP Kinase Kinase Kinase 7
chemical_list: D000498:Allyl Compounds; D000893:Anti-Inflammatory Agents; D051546:Cyclooxygenase 2; D015232:Dinoprostone; D051547:Heme Oxygenase-1; D016753:Interleukin-10; D018664:Interleukin-12; D015850:Interleukin-6; D008070:Lipopolysaccharides; D020930:MAP Kinase Kinase Kinases; D008565:Membrane Proteins; D020928:Mitogen-Activated Protein Kinases; D016660:NAD(P)H Dehydrogenase (Quinone); D051267:NF-E2-Related Factor 2; D016328:NF-kappa B; D052247:Nitric Oxide Synthase Type II; D010936:Plant Extracts; D051057:Proto-Oncogene Proteins c-akt; D017382:Reactive Oxygen Species; D013440:Sulfides; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D000099151:MAP Kinase Kinase Kinase 7; C495636:Nfe2l2 protein, mouse; C042577:diallyl trisulfide; C496317:Nos2 protein, mouse; C496542:Hmox1 protein, mouse; C077623:Ptgs2 protein, mouse; C491732:Nqo1 protein, mouse
keywords: Garlic organosulfur compounds; Inflammatory mediators; MAPK; NF-κB; TGF-β-activated kinase