Korean Journal of Veterinary Research (대한수의학회지)

The Korean Society of Veterinary Science (대한수의학회)
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Solanum lycopersicum (tomato) ethanol extract elicits anti-inflammatory effects via the nuclear factor kappa B pathway and rescues mice from septic shock

  • Saba, Evelyn (Department of Veterinary Medicine, College of Veterinary Medicine, Kyungpook National University) ;
  • Oh, Mi-Ju (Department of Veterinary Medicine, College of Veterinary Medicine, Kyungpook National University) ;
  • Kwak, Dongmi (Department of Veterinary Medicine, College of Veterinary Medicine, Kyungpook National University) ;
  • Roh, Seong-Soo (College of Korean Medicine, Daegu Hanny University) ;
  • Kwon, Hyuk-Woo (Department of Veterinary Medicine, College of Veterinary Medicine, Kyungpook National University) ;
  • Kim, Sung-Dae (Department of Veterinary Medicine, College of Veterinary Medicine, Kyungpook National University) ;
  • Rhee, Man Hee (Department of Veterinary Medicine, College of Veterinary Medicine, Kyungpook National University)
  • Received : 2017.03.21
  • Accepted : 2017.05.19
  • Published : 2017.06.30
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Abstract

Solanum lycopersicum, commonly known as tomato, is widely used in raw, cooked, or liquid forms because it contains nutritional compounds that are beneficial for human health, including carotenoids, lycopene, ascorbic acid, vitamins, and minerals. The tomato is perhaps the most widely studied fruit, especially with respect to its cardioprotective effects. In this study, we aimed to identify the anti-inflammatory mechanisms by which the tomato elicits its anti-inflammatory properties. We treated murine macrophage RAW 264.7 cells with a tomato ethanol extract and performed various biochemical assays including nitric oxide inhibition, cell viability, RNA extraction, expression of pro-inflammatory mediators and cytokines, and immunoblotting, as well we assessed cell survival rates. Our results have shown for the first time that a tomato ethanol extract treatment can suppress nitric oxide production in a dose-dependent manner without cytotoxicity. Moreover, it inhibits the expression of pro-inflammatory mediators and cytokines and elicits its anti-inflammatory effects via the nuclear factor kappa-light-chain-enhancer of activated B cells ($NF-{\kappa}B$) and mitogen-activated protein kinase (MAPK) pathways. In addition, administration of tomato syrup potently rescued mice from septic shock induced by lipopolysaccharide injection. Collectively, our results elucidate details regarding the anti-inflammatory mechanisms of tomato.

Keywords

References

  1. Agarwal A, Shen H, Agarwal S, Rao AV. Lycopene content of tomato products: its stability, bioavailability and in vivo antioxidant properties. J Med Food 2001, 4, 9-15. https://doi.org/10.1089/10966200152053668
  2. Arab L, Steck S. Lycopene and cardiovascular disease. Am J Clin Nutr 2000, 71 (6 Suppl), 1691S-1695S; discussion 1696S-1697S. https://doi.org/10.1093/ajcn/71.6.1691S
  3. Bansal P, Gupta SK, Ojha SK, Nandave M, Mittal R, Kumari S, Arya DS. Cardioprotective effect of lycopene in the experimental model of myocardial ischemia-reperfusion injury. Mol Cell Biochem 2006, 289, 1-9. https://doi.org/10.1007/s11010-006-9141-7
  4. Basu A, Imrhan V. Tomatoes versus lycopene in oxidative stress and carcinogenesis: conclusions from clinical trials. Eur J Clin Nutr 2007, 61, 295-303.
  5. Bignotto L, Rocha J, Sepodes B, Eduardo-Figueira M, Pinto R, Chaud M, de Carvalho J, Moreno H Jr, Mota-Filipe H. Anti-inflammatory effect of lycopene on carrageenaninduced paw oedema and hepatic ischaemia-reperfusion in the rat. Br J Nutr 2009, 102, 126-133. https://doi.org/10.1017/S0007114508137886
  6. Camara M, Matallana MC, Sanchez-Mata MC, Ayue RL, Labra E. Lycopene and hydroxymethylfurfural (HMF) evaluation in tomato products. Acta Hortic 2003 613, 365-371.
  7. Chen C, Chen YH, Lin WW. Involvement of p38 mitogenactivated protein kinase in lipopolysaccharide-induced iNOS and COX-2 expression in J774 macrophages. Immunology 1999, 97, 124-129. https://doi.org/10.1046/j.1365-2567.1999.00747.x
  8. Driscoll KE, Carter JM, Hassenbein DG, Howard B. Cytokines and particle-induced inflammatory cell recruitment. Environ Health Perspect 1997, 105 (Suppl 5), 1159-1164. https://doi.org/10.1289/ehp.97105s51159
  9. Ellinger S, Ellinger J, Stehle P. Tomatoes, tomato products and lycopene in the prevention and treatment of prostate cancer: do we have the evidence from intervention studies? Curr Opin Clin Nutr Metab Care 2006, 9, 722-727. https://doi.org/10.1097/01.mco.0000247470.64532.34
  10. Gilroy DW, Lawrence T, Perretti M, Rossi AG. Inflammatory resolution: new opportunities for drug discovery. Nat Rev Drug Discov 2004, 3, 401-416. https://doi.org/10.1038/nrd1383
  11. Goldring CE, Reveneau S, Pinard D, Jeannin JF. Hyporesponsiveness to lipopolysaccharide alters the composition of NF-${\kappa}B$ binding to the regulatory regions of inducible nitric oxide synthase gene. Eur J Immunol 1998, 28, 2960-2970. https://doi.org/10.1002/(SICI)1521-4141(199809)28:09<2960::AID-IMMU2960>3.0.CO;2-B
  12. Gomes A, Fernandes E, Lima JLFC, Mira L, Corvo ML. Molecular mechanisms of anti-inflammatory activity mediated by flavonoids. Curr Med Chem 2008, 15, 1586-1605. https://doi.org/10.2174/092986708784911579
  13. Guha M, Mackman N. LPS induction of gene expression in human monocytes. Cell Signal 2001, 13, 85-94. https://doi.org/10.1016/S0898-6568(00)00149-2
  14. Han CH, Yang CH, Sohn DW, Kim SW, Kang SH, Cho YH. Synergistic effect between lycopene and ciprofloxacin on a chronic bacterial prostatitis rat model. Int J Antimicrob Agents 2008, 31 (Suppl 1), S102-107. https://doi.org/10.1016/j.ijantimicag.2007.07.016
  15. Hodgin KE, Moss M. The epidemiology of sepsis. Curr Pharm Des 2008, 14, 1833-1839. https://doi.org/10.2174/138161208784980590
  16. Jeong D, Irfan M, Saba E, Kim SD, Kim SH, Rhee MH. Water soluble tomato concentrate regulates platelet function via the mitogen-activated protein kinase pathway. Korean J Vet Res 2016, 56, 67-74. https://doi.org/10.14405/kjvr.2016.56.2.67
  17. Kaminska B. MAPK signalling pathways as molecular targets for anti-inflammatory therapy-from molecular mechanisms to therapeutic benefits. Biochim Biophys Acta 2005, 1754, 253-262. https://doi.org/10.1016/j.bbapap.2005.08.017
  18. Kleinert H, Schwarz PM, Forstermann U. Regulation of the expression of inducible nitric oxide synthase. Biol Chem 2003, 384, 1343-1364.
  19. Kreatsoulas C, Anand SS. The impact of social determinants on cardiovascular disease. Can J Cardiol 2010, 26 (Suppl C), 8C-13C. https://doi.org/10.1016/S0828-282X(10)71075-8
  20. Li H, Deng Z, Liu R, Loewen S, Tsao R. Bioaccessibility, in vitro antioxidant activities and in vivo anti-inflammatory activities of a purple tomato (Solanum lycopersicum L.). Food Chem 2014, 159, 353-360. https://doi.org/10.1016/j.foodchem.2014.03.023
  21. Libby P. Inflammatory mechanisms: the molecular basis of inflammation and disease. Nutr Rev 2007, 65, S140-146. https://doi.org/10.1301/nr.2007.dec.S140-S146
  22. Martin GS. Sepsis, severe sepsis and septic shock: changes in incidence, pathogens and outcomes. Expert Rev Anti Infect Ther 2012, 10, 701-706. https://doi.org/10.1586/eri.12.50
  23. Navarrete S, Alarcon M, Palomo I. Aqueous extract of tomato (Solanum lycopersicum L.) and ferulic acid reduce the expression of TNF-${\alpha}$ and IL-$1{\beta}$ in LPS-activated macrophages. Molecules 2015, 20, 15319-15329. https://doi.org/10.3390/molecules200815319
  24. Palozza P, Parrone N, Catalano A, Simone R. Tomato lycopene and inflammatory cascade: basic interactions and clinical implications. Curr Med Chem 2010, 17, 2547-2563. https://doi.org/10.2174/092986710791556041
  25. Rafi MM, Yadav PN, Reyes M. Lycopene inhibits LPSinduced proinflammatory mediator inducible nitric oxide synthase in mouse macrophage cells. J Food Sci 2007, 72, S069-074.
  26. Rao AV, Agarwal S. Role of antioxidant lycopene in cancer and heart disease. J Am Coll Nutr 2000, 19, 563-569. https://doi.org/10.1080/07315724.2000.10718953
  27. Rao AV, Ray MR, Rao LG. Lycopene. Adv Food Nutr Res 2006, 51, 99-164.
  28. Reifen R, Nissenkorn A, Matas Z, Bujanover Y. 5-ASA and lycopene decrease the oxidative stress and inflammation induced by iron in rats with colitis. J Gastroenterol 2004, 39, 514-519. https://doi.org/10.1007/s00535-003-1336-z
  29. Ren JL, Pan JS, Lu YP, Sun P, Han J. Inflammatory signaling and cellular senescence. Cell Signal 2009, 21, 378-383. https://doi.org/10.1016/j.cellsig.2008.10.011
  30. Rothwarf DM, Karin M. The NF-${\kappa}B$ activation pathway: a paradigm in information transfer from membrane to nucleus. Sci STKE 1999, 1999, re1.
  31. Saba E, Jeon BR, Jeong DH, Lee K, Goo YK, Kwak D, Kim S, Roh SS, Kim SD, Nah SY, Rhee MH. A novel Korean red ginseng compound gintonin inhibited inflammation by MAPK and NF-${\kappa}B$ pathways and recovered the levels of mir-34a and mir-93 in RAW 264.7 cells. Evid Based Complement Alternat Med 2015, 2015, 624132.
  32. Shi J, Le Maguer M. Lycopene in tomatoes: chemical and physical properties affected by food processing. Crit Rev Biotechnol 2000, 20, 293-334. https://doi.org/10.1080/07388550091144212
  33. Surh YJ, Chun KS, Cha HH, Han SS, Keum YS, Park KK, Lee SS. Molecular mechanisms underlying chemopreventive activities of anti-inflammatory phytochemicals: down-regulation of COX-2 and iNOS through suppression of NF-${\kappa}B$ activation. Mutat Res 2001, 480-481, 243-268. https://doi.org/10.1016/S0027-5107(01)00183-X
  34. Turini ME, DuBois RN. Cyclooxygenase-2: a therapeutic target. Annu Rev Med 2002, 53, 35-57. https://doi.org/10.1146/annurev.med.53.082901.103952
  35. Zhou HY, Shin EM, Guo LY, Youn UJ, Bae K, Kang SS, Zou LB, Kim YS. Anti-inflammatory activity of 4-methoxyhonokiol is a function of the inhibition of iNOS and COX-2 expression in RAW 264.7 macrophages via NF-${\kappa}B$, JNK and p38 MAPK inactivation. Eur J Pharmacol 2008, 586, 340-349. https://doi.org/10.1016/j.ejphar.2008.02.044