Effects of plant-based Korean food extracts on lipopolysaccharide-stimulated production of inflammatory mediators in vitro

  • Lee, Sun Young (Department of Nutritional Science and Food Management, Ewha Womans University) ;
  • Kim, Yoo-Sun (Department of Nutritional Science and Food Management, Ewha Womans University) ;
  • Lim, Ji Ye (Department of Nutritional Science and Food Management, Ewha Womans University) ;
  • Chang, Namsoo (Department of Nutritional Science and Food Management, Ewha Womans University) ;
  • Kang, Myung-Hee (Department of Food and Nutrition, Hannam University) ;
  • Oh, Se-Young (Department of Food and Nutrition, Kyung Hee University) ;
  • Lee, He-Jin (Department of Food and Nutrition, Hannam University) ;
  • Kim, Hyesook (Department of Nutritional Science and Food Management, Ewha Womans University) ;
  • Kim, Yuri (Department of Nutritional Science and Food Management, Ewha Womans University)
  • Received : 2013.10.29
  • Accepted : 2013.11.10
  • Published : 2014.06.01


BACKGROUND/OBJECTIVES: The traditional Korean diet is plant-based and rich in antioxidants. Previous studies have investigated the potential health benefits of individual nutrients of Korean foods. However, the cumulative effects of a Korean diet on inflammation remain poorly understood. Therefore, the aim of this study was to investigate the anti-inflammatory effects of a plant-based Korean diet. MATERIALS/METHODS: Using data from the Fifth Korean National Health and Nutrition Examination Survey, 75 individual plant food items were selected which represent over 1% of the total diet intake of the Korean diet. These items were classified into ten different food groups, and the vegetable (Veg) and fruit (Fruit) groups were studied based on their high antioxidant capacity. For comparison, a mixture of all ten groups (Mix) was prepared. To produce a model of inflammation with which to test these Veg, Fruit, and Mix plant-based Korean food extracts (PKE), RAW264.7 macrophages were treated with lipopolysaccharide (LPS). RESULTS: Levels of nitric oxide (NO) and prostaglandin $E_2$ ($PGE_2$), as well as protein expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) were found to be lower following PKE treatment. Furthermore, PKE treatment was found to suppress tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) and interleukin-6 (IL-6) via the nuclear transcription factor kappa-B ($NF-{\kappa}B$) signaling pathway. Overall, the Mix group exhibited the greatest anti-inflammatory effects compared with Veg and Fruit PKE group. CONCLUSIONS: Inhibition of LPS-induced pro-inflammatory mediators by the PKE tested was found to involve an inhibition of NF-kB activation. Moreover, PKE tested have the potential to ameliorate various inflammation-related diseases by limiting the excessive production of pro-inflammatory mediators.


  1. Shapira L, Soskolne WA, Houri Y, Barak V, Halabi A, Stabholz A. Protection against endotoxic shock and lipopolysaccharide-induced local inflammation by tetracycline: correlation with inhibition of cytokine secretion. Infect Immun 1996;64:825-8.
  2. Zhang T, Sun L, Liu R, Zhang D, Lan X, Huang C, Xin W, Wang C, Zhang D, Du G. A novel naturally occurring salicylic acid analogue acts as an anti-inflammatory agent by inhibiting nuclear factorkappaB activity in RAW264.7 macrophages. Mol Pharm 2012;9: 671-7.
  3. Verma IM. Nuclear factor (NF)-kappaB proteins: therapeutic targets. Ann Rheum Dis 2004;63 Suppl 2:ii57-61.
  4. Chan ED, Riches DW. IFN-gamma + LPS induction of iNOS is modulated by ERK, JNK/SAPK, and p38 (mapk) in a mouse macrophage cell line. Am J Physiol Cell Physiol 2001;280:C441-50.
  5. Brodsky M, Halpert G, Albeck M, Sredni B. The anti-inflammatory effects of the tellurium redox modulating compound, AS101, are associated with regulation of NFkappaB signaling pathway and nitric oxide induction in macrophages. J Inflamm (Lond) 2010;7:3.
  6. Chen CH, Sheu MT, Chen TF, Wang YC, Hou WC, Liu DZ, Chung TC, Liang YC. Suppression of endotoxin-induced proinflammatory responses by citrus pectin through blocking LPS signaling pathways. Biochem Pharmacol 2006;72:1001-9.
  7. Pison U, Max M, Neuendank A, Weissbach S, Pietschmann S. Host defence capacities of pulmonary surfactant: evidence for 'nonsurfactant' functions of the surfactant system. Eur J Clin Invest 1994;24:586-99.
  8. Rahman I, Biswas SK, Kirkham PA. Regulation of inflammation and redox signaling by dietary polyphenols. Biochem Pharmacol 2006; 72:1439-52.
  9. Chiodoni C, Colombo MP, Sangaletti S. Matricellular proteins: from homeostasis to inflammation, cancer, and metastasis. Cancer Metastasis Rev 2010;29:295-307.
  10. Hotamisligil GS, Erbay E. Nutrient sensing and inflammation in metabolic diseases. Nat Rev Immunol 2008;8:923-34.
  11. Mollace V, Colasanti M, Muscoli C, Lauro GM, Iannone M, Rotiroti D, Nistico G. The effect of nitric oxide on cytokine-induced release of PGE2 by human cultured astroglial cells. Br J Pharmacol 1998;124:742-6.
  12. Pettus BJ, Bielawski J, Porcelli AM, Reames DL, Johnson KR, Morrow J, Chalfant CE, Obeid LM, Hannun YA. The sphingosine kinase 1/sphingosine-1-phosphate pathway mediates COX-2 induction and PGE2 production in response to TNF-alpha. FASEB J 2003;17: 1411-21.
  13. Bacher S, Schmitz ML. The NF-kappaB pathway as a potential target for autoimmune disease therapy. Curr Pharm Des 2004;10:2827-37.
  14. Brodsky M, Duran F, Sanhueza J, Giaccone J. II. Hemodynamic study of pulmonary arterial hypertension. Rev Med Chil 1956;84:7-16.
  15. Chanput W, Mes J, Vreeburg RA, Savelkoul HF, Wichers HJ. Transcription profiles of LPS-stimulated THP-1 monocytes and macrophages: a tool to study inflammation modulating effects of food-derived compounds. Food Funct 2010;1:254-61.
  16. Bravo L. Polyphenols: chemistry, dietary sources, metabolism, and nutritional significance. Nutr Rev 1998;56:317-33.
  17. Di Tomo P, Canali R, Ciavardelli D, Di Silvestre S, De Marco A, Giardinelli A, Pipino C, Di Pietro N, Virgili F, Pandolfi A. beta- Carotene and lycopene affect endothelial response to TNF-alpha reducing nitro-oxidative stress and interaction with monocytes. Mol Nutr Food Res 2012;56:217-27.
  18. Middleton E Jr, Kandaswami C, Theoharides TC. The effects of plant flavonoids on mammalian cells: implications for inflammation, heart disease, and cancer. Pharmacol Rev 2000;52:673-751.
  19. Choi EM, Hwang JK. Effects of Morus alba leaf extract on the production of nitric oxide, prostaglandin E2 and cytokines in RAW264.7 macrophages. Fitoterapia 2005;76:608-13.
  20. Kim SH, Oh SY. Cultural and nutritional aspects of traditional Korean diet. World Rev Nutr Diet 1996;79:109-32.
  21. Kesteloot H, Zhang J. Salt consumption during the nutrition transition in South Korea. Am J Clin Nutr 2000;72:199-201.
  22. Lee J, Demissie K, Lu SE, Rhoads GG. Cancer incidence among Korean-American immigrants in the United States and native Koreans in South Korea. Cancer Control 2007;14:78-85.
  23. Gordon BH, Kang MS, Cho P, Sucher KP. Dietary habits and health beliefs of Korean-Americans in the San Francisco Bay Area. J Am Diet Assoc 2000;100:1198-201.
  24. Chon SU, Heo BG, Park YS, Kim DK, Gorinstein S. Total phenolics level, antioxidant activities and cytotoxicity of young sprouts of some traditional Korean salad plants. Plant Foods Hum Nutr 2009; 64:25-31.
  25. Kim NY, Song EJ, Kwon DY, Kim HP, Heo MY. Antioxidant and antigenotoxic activities of Korean fermented soybean. Food Chem Toxicol 2008;46:1184-9.
  26. Ministry of Health and Welfare, Korea Centers for Disease Control and Prevention. Korea Health Statistics 2010: Korea National Health and Nutrition Examination Survey (KNHANES V-1). Cheongwon: Korea Centers for Disease Control and Prevention; 2011.
  27. Lee H, Cho MR, Chang N, Kim Y, Oh S, Kang M. Total antioxidant capacity of the Korean diet. Nutr Res Pract. Forthcoming 2013.
  28. Hayashi H, Tatebe S, Osaki M, Goto A, Sato K, Ito H. Anti-Fas antibody-induced apoptosis in human colorectal carcinoma cell lines: role of the p53 gene. Apoptosis 1998;3:431-7.
  29. Guesdon F, Ikebe T, Stylianou E, Warwick-Davies J, Haskill S, Saklatvala J. Interleukin 1-induced phosphorylation of MAD3, the major inhibitor of nuclear factor kappa B of HeLa cells. Interference in signalling by the proteinase inhibitors 3,4-dichloroisocoumarin and tosylphenylalanyl chloromethylketone. Biochem J 1995;307:287-95.
  30. Park S, Kim J, Kim Y. Mulberry leaf extract inhibits cancer cell stemness in neuroblastoma. Nutr Cancer 2012;64:889-98.
  31. Wilson KT, Ramanujam KS, Mobley HL, Musselman RF, James SP, Meltzer SJ. Helicobacter pylori stimulates inducible nitric oxide synthase expression and activity in a murine macrophage cell line. Gastroenterology 1996;111:1524-33.
  32. Tracey KJ, Cerami A. Tumor necrosis factor: a pleiotropic cytokine and therapeutic target. Annu Rev Med 1994;45:491-503.
  33. Song Y, Joung H. A traditional Korean dietary pattern and metabolic syndrome abnormalities. Nutr Metab Cardiovasc Dis 2012;22:456-62.
  34. Berthet J, Damien P, Hamzeh-Cognasse H, Arthaud CA, Eyraud MA, Zeni F, Pozzetto B, McNicol A, Garraud O, Cognasse F. Human platelets can discriminate between various bacterial LPS isoforms via TLR4 signaling and differential cytokine secretion. Clin Immunol 2012;145:189-200.
  35. Mihara M, Hashizume M, Yoshida H, Suzuki M, Shiina M. IL-6/IL-6 receptor system and its role in physiological and pathological conditions. Clin Sci (Lond) 2012;122:143-59.
  36. Stokkers PC, Camoglio L, van Deventer SJ. Tumor necrosis factor (TNF) in inflammatory bowel disease: gene polymorphisms, animal models, and potential for anti-TNF therapy. J Inflamm 1995;47: 97-103.
  37. Wang Z, Jiang W, Zhang Z, Qian M, Du B. Nitidine chloride inhibits LPS-induced inflammatory cytokines production via MAPK and NF-kappaB pathway in RAW 264.7 cells. J Ethnopharmacol 2012; 144:145-50.
  38. Cruz JR, Monterroso MA, Zeissig OA, Hazendonk AG, Van Wezel AL. Paralytic poliomyelitis in Guatemala. Bol Oficina Sanit Panam 1987;103:123-9.
  39. Appleby SB, Ristimäki A, Neilson K, Narko K, Hla T. Structure of the human cyclo-oxygenase-2 gene. Biochem J 1994;302:723-7.
  40. Chen GY, Tang J, Zheng P, Liu Y. CD24 and Siglec-10 selectively repress tissue damage-induced immune responses. Science 2009;323:1722-5.
  41. Deguchi Y, Kishimoto S. Tumour necrosis factor/cachectin plays a key role in autoimmune pulmonary inflammation in lupus-prone mice. Clin Exp Immunol 1991;85:392-5.
  42. Aggarwal BB, Natarajan K. Tumor necrosis factors: developments during the last decade. Eur Cytokine Netw 1996;7:93-124.
  43. Harre EM, Roth J, Pehl U, Kueth M, Gerstberger R, Hübschle T. Selected contribution: role of IL-6 in LPS-induced nuclear STAT3 translocation in sensory circumventricular organs during fever in rats. J Appl Physiol (1985) 2002;92:2657-66.
  44. Beg AA, Finco TS, Nantermet PV, Baldwin AS, Jr. Tumor necrosis factor and interleukin-1 lead to phosphorylation and loss of I kappa B alpha: a mechanism for NF-kappa B activation. Mol Cell Biol 1993;13:3301-10.
  45. Park OJ, Surh YJ. Chemopreventive potential of epigallocatechin gallate and genistein: evidence from epidemiological and laboratory studies. Toxicol Lett 2004;150:43-56.
  46. Bai SK, Lee SJ, Na HJ, Ha KS, Han JA, Lee H, Kwon YG, Chung CK, Kim YM. beta-Carotene inhibits inflammatory gene expression in lipopolysaccharide-stimulated macrophages by suppressing redoxbased NF-kappaB activation. Exp Mol Med 2005;37:323-34.
  47. Liu D, Shi J, Colina Ibarra A, Kakuda Y, Jun Xue S. The scavenging capacity and synergistic effects of lycopene, vitamin E, vitamin C, and ${\beta}$-carotene mixtures on the DPPH free radical. Lebenson Wiss Technol 2008;41:1344-49.
  48. Liu RH. Health benefits of fruit and vegetables are from additive and synergistic combinations of phytochemicals. Am J Clin Nutr 2003;78:517S-520S.
  49. Karatzi K, Papamichael C, Karatzis E, Papaioannou TG, Voidonikola PT, Vamvakou GD, Lekakis J, Zampelas A. Postprandial improvement of endothelial function by red wine and olive oil antioxidants: a synergistic effect of components of the Mediterranean diet. J Am Coll Nutr 2008;27:448-53.

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