Inhibitory effects and molecular mechanisms of garlic organosulfur compounds on the production of inflammatory mediators
Article first published online: 14 JUN 2013
© 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Molecular Nutrition & Food Research
Volume 57, Issue 11, pages 2049–2060, November 2013
How to Cite
You, S., Nakanishi, E., Kuwata, H., Chen, J., Nakasone, Y., He, X., He, J., Liu, X., Zhang, S., Zhang, B. and Hou, D.-X. (2013), Inhibitory effects and molecular mechanisms of garlic organosulfur compounds on the production of inflammatory mediators. Mol. Nutr. Food Res., 57: 2049–2060. doi: 10.1002/mnfr.201200843
- Issue published online: 28 OCT 2013
- Article first published online: 14 JUN 2013
- Manuscript Accepted: 8 APR 2013
- Manuscript Revised: 7 APR 2013
- Manuscript Received: 20 DEC 2012
- Hunan Agriculture University grant for 100 Intelligent
- Garlic organosulfur compounds;
- Inflammatory mediators;
- TGF-β-activated kinase
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.
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.