한국식품저장유통학회지 (Food Science and Preservation)

  • 제24권8호
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  • Pages.1149-1157
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  • 2017
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  • 3022-5477(pISSN)
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  • 3022-5485(eISSN)
한국식품저장유통학회 (The Korean Society of Food Preservation)
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LPS로 유도된 RAW 264.7 Cell과 마우스 모델에 대한 넓패(Ishige sinicola) 에탄올 추출물의 항염증 효과

Anti-inflammatory effects of Ishige sinicola ethanol extract in LPS-induced RAW 264.7 cell and mouse model

  • 김지혜 (부경대학교 식품공학과/식품연구소) ;
  • 김민지 (부경대학교 식품공학과/식품연구소) ;
  • 김꽃봉우리 (부경대학교 수산과학연구소) ;
  • 박선희 (부경대학교 식품공학과/식품연구소) ;
  • 조광수 (부경대학교 식품공학과/식품연구소) ;
  • 김고은 (부경대학교 식품공학과/식품연구소) ;
  • 쉬 시아오통 (부경대학교 식품공학과/식품연구소) ;
  • 이다혜 (부경대학교 식품공학과/식품연구소) ;
  • 박가령 (부경대학교 식품공학과/식품연구소) ;
  • 안동현 (부경대학교 식품공학과/식품연구소)
  • Kim, Ji-Hye (Department of Food Science and Technology/Institute of Food Science, Pukyong National University) ;
  • Kim, Min-Ji (Department of Food Science and Technology/Institute of Food Science, Pukyong National University) ;
  • Kim, Koth-Bong-Woo-Ri (Institute of Fisheries Sciences, Pukyong National University) ;
  • Park, Sun-Hee (Department of Food Science and Technology/Institute of Food Science, Pukyong National University) ;
  • Cho, Kwang-Su (Department of Food Science and Technology/Institute of Food Science, Pukyong National University) ;
  • Kim, Go-Eun (Department of Food Science and Technology/Institute of Food Science, Pukyong National University) ;
  • XU, Xiaotong (Department of Food Science and Technology/Institute of Food Science, Pukyong National University) ;
  • Lee, Da-Hye (Department of Food Science and Technology/Institute of Food Science, Pukyong National University) ;
  • Park, Ga-Ryeong (Department of Food Science and Technology/Institute of Food Science, Pukyong National University) ;
  • Ahn, Dong-Hyun (Department of Food Science and Technology/Institute of Food Science, Pukyong National University)
  • 투고 : 2017.11.29
  • 심사 : 2017.12.24
  • 발행 : 2017.12.30
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초록

본 연구에서는 넓패 에탄올 추출물의 항염증 효과를 알아보기 위해 RAW 264.7 세포에 LPS로 유도된 염증 반응 in vitro 및 in vivo 실험을 실시하였다. RAW 264.7 세포에 LPS와 함께 세포를 배양하였다. 먼저 MTT assay 실험을 통해 넓패 에탄올 추출물이 모든 농도(0.1, 1, 10, 50, $100{\mu}g/mL$)에서 세포독성을 나타내지 않는 것을 학인 하였다. 또한 모든 농도에서 염증억제 효과를 살펴 본 결과, LPS 처리구는 iNOS, COX-2, NF-${\kappa}B$ 그리고 MAPKs의 발현양을 증가 시켰으나, 넓패 에탄올 추출물의 경우 염증 반응에 관여하는 전사인자인 NF-${\kappa}B$와 MAPKs의 활성을 억제함으로써 항염증 효과를 나타내었다. 마지막으로 넓패 에탄올 추출물의 mast cell의 피부 조직학적 변화를 알아본 결과, control의 경우 진피와 경피의 면적이 확장 되어있고, mast cell의 침윤이 정상 군에 비하여 현저하게 증가함을 알 수 있었다. 반면에 넓패 에탄올 추출물의 경우 대조군에 비해 진피와 경피의 두께가 줄었으며 mast cell의 침윤감소에 효과가 있는 것을 확인하였다. 따라서 모든 결과를 종합하였을 때 넓패 에탄올 추출물이 항염증 치료제 뿐만 아니라 더 나아가 항염증에 유용한 기능성 식품소재로써 가치가 높다고 사료된다.

Inflammation is the first response of the immune system to infection or irritation in our body. The use of medicinal plants has been widely applied as an alternative source for drug development. One of marine natural resources, the anti-inflammatory effect of Ishige sinicola ethanol extract (ISEE), was evaluated by using LPS-induced RAW 264.7 cell and mice model. As a result, the production of nitric oxide (NO) and pro-inflammatory cytokines (IL-6, IL-$1{\beta}$, TNF-${\alpha}$) were inhibited with increasing concentration of ISEE without any cytotoxicity. Furthermore, ISEE suppressed the expression of not only inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), nuclear factor-kappa B (NF-${\kappa}B$) p65, and mitogen-activated protein kinases (MAPKs), including extracellular signal-regulated kinase (ERK) 1/2, p38, and c-Jun N-terminal kinase (JNK) in a dose-dependent manner. In mice ear edema test, the formation of edema was reduced at the highest dosage of ISEE and the reduction of the number of infiltrated mast cells was observed in histological analysis. These results indicate that ISEE has a potent anti-inflammatory activity and can be used as a pharmaceutical material for many kinds of inflammatory disease.

키워드

참고문헌

  1. Ferrero-Miliani L, Nielsen OH, Andersen PS, Girardin SE (2007) Chronic inflammation: importance of NOD2 and NALP3 in interleukin-$1{\beta}$ generation. Clin Exp Immunol, 147, 227-253
  2. Ljung T, Lundberg S, Varsanyi M, Ohansson C, Schmidt PT, Herulf M, Lundberg JO, Hellstrom PM (2006) Rectal nitric oxide as biomarker in the treatment of inflammatory bowel disease: responders versus non-responder. World J Gastroenterol, 12, 3386-3392 https://doi.org/10.3748/wjg.v12.i21.3386
  3. Wu MJ, Wang L, Ding HY, Weng CY, Yen JH (2004) Glossogyne tenuifolia acts to inhibit inflammatory mediator production in a macrophage cell line by downregulating LPS-induced NF-${\kappa}B$. J Biomed Sci, 11, 186-199
  4. Nathan CF (1987) Secretory products of macrophages. J Clin Invest, 79, 319-326 https://doi.org/10.1172/JCI112815
  5. Jaffrey SR, Snyder SH (1995) Nitric oxide: a neural messenger. Annu Rev Cell Dev Biol, 11, 417-440 https://doi.org/10.1146/annurev.cb.11.110195.002221
  6. Ghosh S, Hayden MS (2008) New regulators of NF-${\kappa}B$ in inflammation. Nat Rev Immunol, 8, 837-848 https://doi.org/10.1038/nri2423
  7. Storck M, Schilling M, Burkhardt K, Prestel R, Abendroth D, Hammer C (1994) Production of proinflammatory cytokines and adhesion molecules in ex-vivo xenogeneic kidney perfusion. Transpl Int, 7, S647-S649 https://doi.org/10.1111/j.1432-2277.1994.tb01464.x
  8. Majdalawieh A, Ro HS (2010) Regulation of $I{\kappa}B{\alpha}$ function and NF-${\kappa}B$ signaling: AEBP1 is a novel proinflammatory mediator in macrophages. Mediators Inflammation, 2010, 1-27
  9. Yang H, Oh KH, Yoo YC (2015) Anti-inflammatory effect of hot water extract of aronia fruits in LPS-stimulated RAW 264.7 macrophages. J Korean Soc Food Sci Nutr, 44, 7-13 https://doi.org/10.3746/jkfn.2015.44.1.007
  10. Nagayama K, Iwamura Y, Shibata T, Hirayama I, Nakamura T (2002) Bactericidal activity of phlorotannins from the brown alga Ecklonia kurome. J Antimicrob Chemother, 50, 889-893 https://doi.org/10.1093/jac/dkf222
  11. Ryu BH, Kim DS, Cho KJ, Sin DB (1989) Antitumor activity of seaweeds toward sarcoma-180. Korean J Food Sci Technol, 21, 595-600
  12. Choo KS, Lee HN, Shin SA Kim HJ, Park YS, Kim SK, Jung JY (2016) Induction of growth inhibition and apoptosis in human cancer cells by a brown algae extract. J Life Sci, 26, 555-562 https://doi.org/10.5352/JLS.2016.26.5.555
  13. Cho BO, Ryu HW, So YK, Jin CH, Byun MW, Kim WG, Jeong IY (2012) Ishige sinicola extracts induce apoptosis via activation of a caspase cascade in Human hela cells. J Korean Soc Food Sci Nutr, 41, 901-906 https://doi.org/10.3746/jkfn.2012.41.7.901
  14. Kim MJ, Bae NY, Kim KBWR, Kim JH, Park SH, Jang MR, Ahn DH (2016) Anti-inflammatory effect of Chondrus nipponicus yendo ethanol extract on lipopolysaccharide-induced inflammatory responses in RAW 264.7 cells. J Korean Soc Food Sci Nutr, 45, 194-201 https://doi.org/10.3746/jkfn.2016.45.2.194
  15. Kim MJ, Bea NY, Kim KBWR. Park JH, Park SH, Cho YJ, Ahn DH (2015) Anti-inflammatory effect of water extract from tuna heart on lipopolysaccharide-induced inflammatory responses in RAW 264.7 Cells. Korean Soc Biotechnol Bioeng J, 30, 326-331
  16. Kim MJ, Bae NY, Kim KBWR, Park JH, Park SH, Choi JS, Ahn DH (2016) Anti-inflammatory effect of Grateloupia imbricata Holmes ethanol extract on LPS-induced RAW 264.7 cells. J Korean Soc Food Sci Nutr, 45, 181-187 https://doi.org/10.3746/jkfn.2016.45.2.181
  17. Clark D, Durner J, Navarre DA, Klessig DF (2000) Nitric oxide inhibition of tobacco catalase and ascorbate peroxidase. MPMI, 13, 1380-1384 https://doi.org/10.1094/MPMI.2000.13.12.1380
  18. Weisz A, Cicatiello L, Esumi H (1996) Regulation of the mouse inducible-type nitric oxide synthase gene promoter by interferon-${\gamma}$, bacterial lipopolysaccharide, and NG-monomethyl-L-arginine. Biochem J, 316, 209-215 https://doi.org/10.1042/bj3160209
  19. Szelenyi J (2001) Cytokines and the central nervous system. Brain Res Bull, 54, 329-338 https://doi.org/10.1016/S0361-9230(01)00428-2
  20. Choi YS, Won JY, Yoo IW, Shin JW, Kim SJ, Sohn NW (2013) Effect of tetramethylpyrazine on proinflammatory cytokine expressions in mouse brain tissue following intracerebroventricular lipopolysaccharide treatment. Korea J Herbol, 28, 83-90
  21. Li Y, Wu Q, Deng Y, Lv H, Qiu J, Chi G, Feng H (2015) D(-)-Salicin inhibits the LPS-induced inflammation in RAW 264.7 cells and mouse models. Int Immunopharmacol, 26, 286-294 https://doi.org/10.1016/j.intimp.2015.04.016
  22. Park, SH, Jeong JH, Park BJ, Jeong TH (2015) Anti-inflammatory effect of Fallopia sachalinensis RonseDecr. fruit. J Soc Cosmet Sci Korea, 41, 237-241
  23. Hinz B, Brune K (2002) Cyclooxygenase-2-10 years later. J Pharmacol Exp Ther, 300, 367-375 https://doi.org/10.1124/jpet.300.2.367
  24. Kim SH, Yun JW, Lee YH, Cheon EJ (2009) Polymorphisms of tumor necrosis factor-alpha promoter gene in Kawasaki disease and relation to the risk of coronary artery lesion. Korean J Pediatr, 52, 476-480 https://doi.org/10.3345/kjp.2009.52.4.476
  25. Kim DH, Hwang EY, Son JH (2013) Anti-inflammatory activity of Carthamus tinctorious seed extracts in RAW264.7 cells. J Life Sci, 23, 55-62 https://doi.org/10.5352/JLS.2013.23.1.55
  26. Noh KH, Jang JH, Min KH, Chinzoring R, Lee MO, Song YS (2011) Suppressive effect of green tea seed coat ethyl acetate fraction on inflammation and its mechanism in RAW 264.7 macrophage cell. J Korean Soc Food Sci Nutr, 40, 625-634 https://doi.org/10.3746/jkfn.2011.40.5.625
  27. Bak MJ, Jeong JH, Kang HS, Jin KS, Ok S, Jeong WS (2009) Cedrela sinensis leaves suppress oxidative stress and expressions of iNOS and COX-2 via MAPK signaling pathways in RAW 264.7 cells. J Food Sci Nutr, 14, 269-276
  28. Kim BW, Kim JI, Kim HR, Byun DS (2014) Anti-inflammatory effect of an ethyl acetate fraction from Myagropsis yendoi on lipopolysaccharides- stimulated RAW 264.7 Cells. Korean J Fish Aquat Sci, 47, 527-536
  29. Chung HJ, Lee HS, Shin JS, Lee SH, Park BM, Youn YS, Lee SK (2010) Modulation of acute and chronic inflammatory processes by a traditional medicine preparation GCSB-5 both in vitro and in vivo animal models. J Ethnopharmacol, 130, 450-459 https://doi.org/10.1016/j.jep.2010.05.020
  30. Eum WS, Lee KJ, Kim DW, Lim SS, Kang IJ, Park J, Choi SY (2013) Anti-inflammatory effects of extracts from Caesalpinia sappan L. on skin inflammation. J Korean Soc Food Sci Nutr, 42, 384-388 https://doi.org/10.3746/jkfn.2013.42.3.384
  31. Amin K (2012) The role of mast cells in allergic inflammation. Respir Med, 106, 9-14 https://doi.org/10.1016/j.rmed.2011.09.007
  32. Rocca B, FitzGerald GA (2002) Cyclooxygenases and prostaglandins: shaping up the immune response. Int Immunopharmacol, 2, 603-630 https://doi.org/10.1016/S1567-5769(01)00204-1
  33. Seo UK, Lee JI, Park JH, Park YK (2008) The ethyl acetate extract of north Kangwhal (Ostericum koreanum) attenuates the inflammatory responses in PMA/A23187-stimulated mast cells. Korea J Herbol, 23, 81-89