RRC ID 44476
Author You S, Nakanishi E, Kuwata H, Chen J, Nakasone Y, He X, He J, Liu X, Zhang S, Zhang B, Hou DX.
Title Inhibitory effects and molecular mechanisms of garlic organosulfur compounds on the production of inflammatory mediators.
Journal Mol Nutr Food Res
Abstract SCOPE: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.
METHODS AND 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.
CONCLUSION: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.
Volume 57(11)
Pages 2049-60
Published 2013-11-1
DOI 10.1002/mnfr.201200843
PMID 23766070
MeSH Allyl Compounds / pharmacology* Animals Anti-Inflammatory Agents / pharmacology* Cell Line, Tumor Cyclooxygenase 2 / metabolism Dinoprostone / metabolism Disease Models, Animal Down-Regulation Edema / prevention & control Garlic / chemistry* Heme Oxygenase-1 / metabolism Inflammation / drug therapy Interleukin-10 / metabolism Interleukin-12 / metabolism Interleukin-6 / metabolism Lipopolysaccharides / adverse effects MAP Kinase Kinase Kinases / antagonists & inhibitors MAP Kinase Kinase Kinases / metabolism Membrane Proteins / metabolism Mice Mitogen-Activated Protein Kinases / antagonists & inhibitors Mitogen-Activated Protein Kinases / metabolism NAD(P)H Dehydrogenase (Quinone) / metabolism NF-E2-Related Factor 2 / metabolism NF-kappa B / antagonists & inhibitors NF-kappa B / metabolism Nitric Oxide Synthase Type II / metabolism Phosphorylation Plant Extracts / pharmacology* Proto-Oncogene Proteins c-akt / antagonists & inhibitors Proto-Oncogene Proteins c-akt / metabolism Reactive Oxygen Species Signal Transduction / drug effects Sulfides / pharmacology* Transforming Growth Factor beta / metabolism Tumor Necrosis Factor-alpha / metabolism
IF 4.653
Times Cited 34
Human and Animal Cells