Food Science and Preservation (한국식품저장유통학회지)

The Korean Society of Food Preservation (한국식품저장유통학회)
권호 표지
DOI QR코드

DOI QR Code

Protective effects of quality certified traditional Doenjang in Korea on TNF-α-induced vascular inflammation in human umbilical vein endothelial cells

혈관내피세포에서 TNF-α 자극에 의해 유도되는 혈관염증에 대한 전통식품 품질인증 된장의 효능 평가

  • Kim, Eun-Ju (Fermentated Food Science Division, National Institute of Agricultural Sciences, RDA) ;
  • Jang, Yeon-Jeong (Fermentated Food Science Division, National Institute of Agricultural Sciences, RDA) ;
  • Kim, So-Young (Fermentated Food Science Division, National Institute of Agricultural Sciences, RDA) ;
  • Choi, Hye-Sun (Fermentated Food Science Division, National Institute of Agricultural Sciences, RDA) ;
  • Park, Shin-Young (Fermentated Food Science Division, National Institute of Agricultural Sciences, RDA)
  • 김은주 (농촌진흥청 국립농업과학원 농식품자원부 발효식품과) ;
  • 장연정 (농촌진흥청 국립농업과학원 농식품자원부 발효식품과) ;
  • 김소영 (농촌진흥청 국립농업과학원 농식품자원부 발효식품과) ;
  • 최혜선 (농촌진흥청 국립농업과학원 농식품자원부 발효식품과) ;
  • 박신영 (농촌진흥청 국립농업과학원 농식품자원부 발효식품과)
  • Received : 2016.04.19
  • Accepted : 2016.06.13
  • Published : 2016.06.30
Download PDF
⟨ Previous Next ⟩

Abstract

Anti-atherogenic effects in tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$)-stimulated human umbilical vein endothelial cells (HUVEC) are involved in the suppression of oxidative stress, cell adhesion molecules, and pro-inflammatory factors. This study investigated the vascular inflammation inhibitory activity of traditional Doenjang plays a key role in the pathogenesis and progression of atherosclerosis. The protective effects of Korean Deonjang was investigated on the expression of cell adhesion molecules (CAMs) in tumor necrosis factor (TNF)-${\alpha}$-induced human umbilical vascular endothelial cells (HUVECs). Deonjang extracts (20, 50, $100{\mu}g/mL$) decreased the expression of 20 ng/mL TNF-${\alpha}$-induced vascular cell adhesion molecule (VCAM)-1 intracellular adhesion molecule (ICAM)-1 proteins, and their corresponding mRNA levels. Nitric oxides (NO) produced by endothlial nitric oxides synthase (eNOS) dilated blood vessels, which had protective effects against platelet and leukocyte adhesion. While TNF-${\alpha}$-induced suppressed the production of nitric oxide in HUVECs, Doenjang restored NO production in HUVECs. In addition, Deonjang reduced the TNF-${\alpha}$-induced expression of inducible NO synthase (iNOS) and cyclooxygenase (COX)-2 mRNA levels. These results suggested that Doenjang can inhibited the production of cell adhesion molecules and inflammatory mediators, which could be a potential candidate for preventing atherosclerosis.

DJ#3과 DJ#13은 항염증질환 소재로서 가능성을 확인하고자 국내 전통식품 풀질인증 된장에서 장기간 숙성된장으로 선발된 시료이다. DJ#3과 DJ#13 추출물의 세포독성을 살펴보기 위하여 혈관내피세포를 이용하여 세포의 생존율을 살펴본 결과 DJ#3과 DJ#13 추출물 모두 $100{\mu}g/mL$의 농도까지 전혀 독성을 나타내지 않았다. 또한 DJ#3과 DJ#13 추출물의 항염증 효과를 TNF-${\alpha}$에 의해 활성화된 혈관내피세포에서의 NO 생성, 염증관련 단백질 발현과 mRNA 유전자 발현의 변화를 통하여 확인하였다. 혈관내피세포에 TNF-${\alpha}$를 처리한 결과 NO의 함량이 유의적으로 감소하였다가 DJ#3과 DJ#13 추출물(20, 50, $100{\mu}g/mL$)을 처리하였을 때 유의성은 없으나 증가하였다. 세포배양액내 VCAM-1, ICAM-1 발현을 확인한 결과 혈관내피세포에 TNF-${\alpha}$를 처리한 군에서 증가된 VCAM-1 발현이 DJ#3 추출물 20, $50{\mu}g/mL$에서 유의성 있는 감소를 보였다. 또한 DJ#3 추출물은 NO 생성과 연관 있는 eNOS mRNA의 발현을 농도 의존적으로 증가하였으며, iNOS mRNA의 발현은 농도 의존적으로 감소하였으며 이는 NO 생성 증가가 iNOS의 발현억제를 경유한 것으로 사료된다. 또한 다수의 항염증 약물들의 작용기전이 되는 COX-2의 생성억제를 살펴본 결과 DJ#3 추출물은 TNF-${\alpha}$에 의해 발현되는 COX-2 단백질의 발현을 억제하였음을 확인할 수 있었다. 또한, DJ#3 추출물은 CAMs 단백질 및 mRNA 발현율의 감소됨을 보였다, 이상의 결과로 보아, DJ#3 추출물은 혈관내피세포에서 TNF-${\alpha}$로 유도된 혈관염증을 감소하는 효과를 가지고 있으며, 항염증물질의 연구에 기초 자료로 활용이 가능할 것으로 기대된다. 또한 염증과 관련된 cytokine 및 단백질 발현 메커니즘에 대한 추가적인 연구가 필요할 것으로 판단된다.

Keywords

References

  1. Lim SY, Rhee SH, Park KY (2004) Inhibitory effect of methanol extract of Doenjang on growth and DNA synthesis of human cancer cells. J Korean Soc Food Sci Nutr, 33, 936-940 https://doi.org/10.3746/jkfn.2004.33.6.936
  2. Lim SY, Kim KH, Park KY, Lee SH (2007) Effect of solvent fractions from Doenjang on antimutagenicity, growth of tumor cells and production of interleukin-2. J Life Sci, 17, 791-797 https://doi.org/10.5352/JLS.2007.17.6.791
  3. Kim MJ, Rhee HS (1990) Studies on the changes of taste compounds during soy paste fermentation. Korean J Food Cook Sci, 6, 1-8
  4. Coward L, Barnes NC, Setchell KDR, Barnes S (1993) Genistein, daidzein, and their ${\beta}$-glycoside conjugates: antitumor isoflavones in soybean foods from American and Asian diets. J Agric Food Chem, 41, 1961-1967 https://doi.org/10.1021/jf00035a027
  5. Hamalainen M, Nieminen R, Vuorela P, Heinonen M, Moilanen E (2007) Anti-inflammatory effects of flavonoids: genistein, kaempferol, quercetin, and daidzein inhibit STAT-1 and NF-${\kappa}$B activations, whereas flavone, isorhamnetin, naringenin, and pelargonidin inhibit only NF-${\kappa}$B activation along with their inhibitory effect on iNOS expression and NO production in activated macrophages. Mediators Inflamm, 2007, 45673
  6. Ungar Y, Osundahunsi OF, Shimoni E (2003) Thermal stability of genistein and daidzein and its effect on their antioxidant activity. J Agric Food Chem, 51, 4394-4399 https://doi.org/10.1021/jf034021z
  7. Guo JM, Xiao BX, Liu DH, Grant M, Zhang S, Lai YF, Guo YB, Liu Q (2004) Biphasic effect of daidzein on cell growth of human colon cancer cells. Food Chem Toxicol, 42, 1641-1646 https://doi.org/10.1016/j.fct.2004.06.001
  8. Park KY, Moon SH, Baik HS, Cheigh HS (1990) Antimutagenic effect of Doejang (Korean fermented soy paste) toward aflatoxin. J Korean Soc Food Sci Nutr, 19, 158-162
  9. Cui CB, Lee EY, Lee DS, Ham SS (2002) Antimutageniic and anticancer effects of ethanol extract from Korean traditional Doenjang added sea tangle. J Korean Soc Food Sci Nutr, 31, 322-328 https://doi.org/10.3746/jkfn.2002.31.2.322
  10. Kim SH (1998) New trends of studying on potential activities of Doenjang-fibrinolytic activity. Korea Soybean Digest, 15, 8-15
  11. Lee BK, Jang YS, Yi YS, Chung KS, Choi SY (1997) Immunomodulators extracted from Korean-style fermented soybean paste and their function. Isolation of B cell mitogen from Korean-style fermented soybean paste. Korean J Immonol, 19, 559-569
  12. Suh HJ, Suh DB, Chung SH, Whang JH, Sung HJ, Yang HC (1994) Purification of ACE inhibitor from soybean paste. Appl Biol Chem, 37, 441-446
  13. Hwang JH (1997) Angiotensin I converting enzyme inhibitory effect of Doenjang fermented by B. subtilis SCB-3 isolated from Meju, Korean traditional food. J Koeran Soc Food Sci Nutr, 26, 775-783
  14. Yang BK, Jeong SC, Hur NJ, Ha SO, Kim KY, Kym KH, Yun JW, Song CH (2000) Hypoglycemic effect of extracts of soybean paste containing mycelia of mushrooms in streptozotocin-induced diabetic rats. Korean J Mycol, 28, 126-129
  15. Choe GS, Lim SY, Choi JS (1998) Antioxidant and nitrite scavenging effect of soybean, Meju and Doenjang. Korean J Life Sci, 8, 473-478
  16. Kim MH, Im SS, Kim SH, Kim GE, Lee JH (1994) Antioxidative materials in domestic Meju and Doenjang 2. Separation of lipophilic brown pigment and their antioxidative activity. J Korean Soc Food Nutr, 23, 251-260
  17. Choi UK, Ji WD, Chung HC, Choi DH, Chung YG (1997) Optimum condition for pigment production and antioxidative activity of the products by Bacillus subtilis DC-2 with response surface methodology. J Korean Soc Food Sci Nutr, 26, 620-624
  18. Ross R (1995) Cell biology of atherosclerosis. Annu Rev Physiol, 57, 791-804 https://doi.org/10.1146/annurev.ph.57.030195.004043
  19. Lee ES, Ju HK, Moon TC, Lee EK, Jahng YD, Lee SH, Son JK, Baek SH, Chang HW (2004) Inhibition of nitric oxide and tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) production by propenone compound through blockade of nuclear factor (NF)-${\kappa}$B activation in cultured murine macrophages. Biol Pharm Bull, 27, 617-620 https://doi.org/10.1248/bpb.27.617
  20. Lee TH, Kwak HB, Kim HH, Lee ZH, Chung DK, Baek NI, Kim JY (2007) Methanol extracts of Stewartia koreana inhibit cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) gene expression by blocking NF-${\kappa}$B transactivation in LPS-activated RAW 264.7 cells. Mol Cells, 23, 398-404
  21. Nathan C (1992) Nitric oxide as a secretory product of mammalian cells. FASEB J, 6, 3051-3064 https://doi.org/10.1096/fasebj.6.12.1381691
  22. Mohamed AK, Bierhaus A, Schiekofer S, Tritschler H, Ziegler R, Nawroth PP (1999) The role of oxidative stress and NF-${\kappa}$B activation in late diabetic complications. Biofactors, 10, 157-167 https://doi.org/10.1002/biof.5520100211
  23. Chen JW, Chen YH, Lin FY, Chen YL, Lin SJ (2003) Ginkgo biloba extract inhibits tumor necrosis factor-${\alpha}$ -induced reactive oxygen species generation, transcription factor activation, and cell adhesion molecule expression in human aortic endothelial cells. Arterioscler Thromb Vasc Biol, 23, 1559-1566 https://doi.org/10.1161/01.ATV.0000089012.73180.63
  24. Kanters E, Pasparakis M, Gijbels MJ, Vergouwe MN, Partouns-Hendriks I, Fijneman RJ, Clausen BE, Forster I, Kockx MM, Rajewsky K, Kraal G, Hofker MH, de Winther MP (2003) Inhibition of NF-${\kappa}$B activation in macrophages increases atherosclerosis in LDL receptor-deficient mice. J Clin Invest, 112, 1176-1185 https://doi.org/10.1172/JCI200318580
  25. Kunsch C, Luchoomun J, Grey JY, Olliff LK, Saint LB, Arrendale RF, Wasserman MA, Saxena U, Medford RM (2004) Selective inhibition of endothelial and monocyte redox-sensitive genes by AGI-1067: a novel antioxidant and anti-inflammatory agent. J Pharmacol Exp Ther, 308, 820-829
  26. Huh JI, Jin SY (2011) A survey on the perception of agricultural food accreditation and traditional food quality certification. J Korean Soc Food Cult, 26, 220-229
  27. National Agricultural Products Quality Management Service (2012) Traditional Food Standards. Anyang, Korea, p 88-93, p 99-100
  28. Kang JE, Choi HS, Choi HS, Park SY, Song J, Choi JH, Yeo SH, Jung ST (2013) The quality characteristics of commercial Deonjang certified for traditional foods. Korean J Community Living Sci, 24, 537-542 https://doi.org/10.7856/kjcls.2013.24.4.537
  29. Je JY, Park PJ, Kim EK, Ahn CB (2009) Antioxidant and angiotensin I converting enzyme inhibitory activity of Bambusae caulis in liquamen. Food Chem, 113, 932-935 https://doi.org/10.1016/j.foodchem.2008.08.022
  30. Lee SJ, Kim EK, Kim YS, Hwang JW, Lee KH, Choi DK, Kang H, Moon SH, Jeon BT, Park PJ (2012) Purification and characterization of a nitric oxide inhibitory peptide from Ruditapes philippinarum. Food Chem Toxicol, 50, 1660-1666 https://doi.org/10.1016/j.fct.2012.02.021
  31. Bradford MM (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem, 72, 248-254 https://doi.org/10.1016/0003-2697(76)90527-3
  32. Kim JY, Jung KS, Jeong HG (2004) Suppressive effects of the kahweol and cafestol on cyclooxygenase-2 expression in macrophages. FEBS Lett, 569, 321-326 https://doi.org/10.1016/j.febslet.2004.05.070
  33. Li H, Forstermann U (2000) Nitric oxide in the pathogenesis of vascular disease. J Pathol, 190, 244-254 https://doi.org/10.1002/(SICI)1096-9896(200002)190:3<244::AID-PATH575>3.0.CO;2-8
  34. Sarkar D, Fisher PB (2006) Molecular mechanisms of aging-associated inflammation. Cancer Lett, 236, 13-23 https://doi.org/10.1016/j.canlet.2005.04.009
  35. Vodovotz Y, Russell D, Xie QW, Bogdan C, Nathan C (1995) Vesicle membrane association of nitric oxide synthase in primary mouse macrophage. J Immunol, 154, 2914-2925
  36. Sung MS, Kim YH, Choi YM, Ham HM, Jeong HS, Lee JS (2011) Anti-inflammatory effect of Erigeron annuus L. flower extract through heme oxygenase-1 induction in RAW 264.7 macrophages. J Korean Soc Food Sci Nutr, 40, 1507-1511 https://doi.org/10.3746/jkfn.2011.40.11.1507
  37. Yoon WJ, Lee JA, Kim KN, Kim JY, Park SY (2007) In vitro anti-inflammatory activity of the Artemisia fukudo extracts in murine macrophage RAW 264.7 cells. Korean J Food Sci Technol, 39, 464-469
  38. Hwang SJ, Ballantyne CM, Sharrett AR, Smith LC, Davis CE, Gotto AM Jr, Boerwinkle E (1997) Circulating adhesion molecules VCAM-1, ICAM-1, and E-selectin in carotid atherosclerosis and incident coronary heart disease cases. Circulation, 96, 4219-4225 https://doi.org/10.1161/01.CIR.96.12.4219
  39. Li H, Cybulsky MI, Gimbrone MA Jr, Libby P (1993) An atherogenic diet rapidly induces VCAM-1, a cytokine-regulatable mononuclear leukocyte adhesion molecule, in rabbit aortic endothelium. Arterioscler Thromb, 13, 197-204 https://doi.org/10.1161/01.ATV.13.2.197
  40. Schmidt A, Goepfert C, Feitsma K, Buddecke E (2002) Lovastatin-stimulated superinduction of E-selectin, ICAM-1 and VCAM-1 in TNF-${\alpha}$ activated human vascular endothelial cells. Atherosclerosis, 164, 57-64 https://doi.org/10.1016/S0021-9150(02)00053-9
  41. Rimbach G, Valacchi G, Canali R, Virgili F (2000) Macrophages stimulated with IFN-${\gamma}$ activate NF-${\kappa}B$ and induce MCP-1 gene expression in primary human endothelial cells. Mol Cell Biol Res Commun, 3, 238-242 https://doi.org/10.1006/mcbr.2000.0219

Cited by

  1. 전북지역 전통 된장의 품질특성 및 항산화 활성 vol.32, pp.6, 2016, https://doi.org/10.9799/ksfan.2019.32.6.598
  2. 대식세포에서 나문재 분말을 함유한 된장의 항염증 효과 vol.32, pp.6, 2019, https://doi.org/10.9799/ksfan.2019.32.6.651