Journal of the Korean Society of Food Science and Nutrition (한국식품영양과학회지)

The Korean Society of Food Science and Nutrition (한국식품영양과학회)
권호 표지
DOI QR코드

DOI QR Code

Anti-Inflammatory Effect of Ethanolic Extract from Polyopes affinis through Suppression of NF-κB and MAPK Activation in LPS-Stimulated RAW 264.7 Cells

LPS로 자극된 대식세포에서의 NF-κB와 MAPK 활성 조절을 통한 참까막살(Polyopes affinis) 에탄올 추출물의 항염증 효과

  • Kim, Min-Ji (Department of Food Science and Tehcnology/Institute of Food Sciences, Pukyong National University) ;
  • Kim, Koth-Bong-Woo-Ri (Department of Food Science and Tehcnology/Institute of Food Sciences, Pukyong National University) ;
  • Park, Sun-Hee (Department of Food Science and Tehcnology/Institute of Food Sciences, Pukyong National University) ;
  • Park, So-Young (Department of Food Science and Tehcnology/Institute of Food Sciences, Pukyong National University) ;
  • Choi, Hyeun-Deok (Institute of Fisheries Sciences, Pukyong National University) ;
  • Choi, Jung-Su (Subdivision of Culinary Arts, Kyungnam College of Information and Technology) ;
  • Jang, Mi-Ran (Health Functional Food Policy Division, Ministry of Food and Drug Safety) ;
  • Im, Moo-Hyeog (Department of Food Science and Biotechnology, Daegu University) ;
  • Ahn, Dong-Hyun (Department of Food Science and Tehcnology/Institute of Food Sciences, Pukyong National University)
  • 김민지 (부경대학교 식품공학과/식품연구소) ;
  • 김꽃봉우리 (부경대학교 식품공학과/식품연구소) ;
  • 박선희 (부경대학교 식품공학과/식품연구소) ;
  • 박소영 (부경대학교 식품공학과/식품연구소) ;
  • 최현덕 (부경대학교 수산과학연구소) ;
  • 최정수 (경남정보대학교 호텔외식조리계열) ;
  • 장미란 (식품의약품안전처 건강기능식품정책과) ;
  • 임무혁 (대구대학교 식품공학과) ;
  • 안동현 (부경대학교 식품공학과/식품연구소)
  • Received : 2016.11.23
  • Accepted : 2017.05.02
  • Published : 2017.05.31
Download PDF
⟨ Previous Next ⟩

Abstract

In this study, the anti-inflammatory effect of Polyopes affinis ethanol extract (PAEE) was investigated using LPS-stimulated RAW 264.7 cells and a croton oil-induced ICR mice model. Treatment with PAEE significantly reduced production of nitric oxide (NO) and pro-inflammatory cytokines [interleukin (IL)-6, tumor necrosis factor $(TNF)-{\alpha}$, and $IL-1{\beta}$] in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. PAEE treatment also reduced expression of inducible NO synthase, cyclooxygenase-2, nuclear $factor-{\kappa}B$, and mitogen-activated protein kinases in LPS-stimulated RAW 264.7 cells. In the croton oil-induced ear edema test, application of PAEE (10~250 mg/kg body weight) reduced ear edema in a dose-dependent manner, and PAEE treatment at 50 mg/kg body weight showed similar inhibitory effects compared with prednisolone (10 mg/kg body weight). Histological analysis revealed reduced dermal thickness and lower number of infiltrated mast cells. These results suggest that PAEE might be used as a promising anti-inflammatory agent for inhibition of LPS-induced inflammation and ear edema formation.

본 연구에서는 참까막살 에탄올 추출물(PAEE)의 항염증 활성을 확인하기 위하여 LPS로 자극된 RAW 264.7 세포에서의 pro-inflammatory cytokine 및 NO의 분비 생성량과 western blot으로 단백질 발현량을 측정하였다. 또한, croton oil로 유도된 귀 부종 모델을 이용하여 알아보았다. RAW 264.7 세포에서 PAEE를 $0.1{\sim}100{\mu}g/mL$ 농도로 처리 시 세포독성을 나타내지 않음을 확인하였다. 그 결과 PAEE는 pro-inflammatory cytokine(IL-6, $TNF-{\alpha}$, $IL-1{\beta}$) 및 NO의 분비량을 농도 의존적으로 억제시켰으며, iNOS와 COX-2의 발현량도 감소시킴을 확인하였다. 이러한 항염증 활성결과는 $NF-{\kappa}B$와 MAPKs 전사인자의 활성 억제에 의한 것으로 확인되었다. 또한, croton oil로 유도된 귀 부종 모델에서 PAEE를 50 mg/kg body weight 처리 시 귀 부종이 prednisolone(10 mg/kg body weight)과 유사한 정도로 억제됨을 확인하였다. 귀 조직 관찰에서도 PAEE는 croton oil에 의해 증가한 진피와 경피의 두께를 감소시켰으며, 진피로 침윤된 mast cell의 수도 감소시켰다. 이 결과를 종합해 보면 참까막살 에탄올 추출물은 $NF-{\kappa}B$와 MAPKs의 활성화 억제를 통해 염증 매개 물질의 생성을 억제시켜 항염증 활성을 나타내는 것으로 확인되었다.

Keywords

References

  1. Nathan C. 2002. Points of control on inflammation. Nature 420: 846-852. https://doi.org/10.1038/nature01320
  2. Medzhitov R. 2008. Origin and physiological roles of inflammation. Nature 454: 428-435. https://doi.org/10.1038/nature07201
  3. Jeong DH, Kim KB, Kim MJ, Kang BK, Ahn DH. 2013. Anti-inflammatory activity of ethanolic extract of Sargassum micracanthum. J Microbiol Biotechnol 23: 1691-1698. https://doi.org/10.4014/jmb.1311.11025
  4. Waetzig V, Czeloth K, Hidding U, Mielke K, Kanzow M, Brecht S, Goetz M, Lucius R, Herdegen T, Hanisch UK. 2005. c-Jun N-terminal kinases (JNKs) mediate pro-inflammatory actions of microglia. Glia 50: 235-246. https://doi.org/10.1002/glia.20173
  5. Jung WK, Heo SJ, Jeon YJ, Lee CM, Park YM, Byun HG, Choi YH, Park SG, Choi IW. 2009. Inhibitory effects and molecular mechanism of dieckol isolated from marine brown alga on COX-2 and iNOS in microglial cells. J Agric Food Chem 57: 4439-4446. https://doi.org/10.1021/jf9003913
  6. Kim MJ, Bae NY, Bark SW, Kim KBWR, Park JH, Park SH, Ahn DH. 2015. Anti-inflammatory effect of alginate oligosaccharides produced by an alginate-degrading enzyme from Shewanella oneidensis PKA1008 on LPS-induced RAW 264.7 cells. Korean J Fish Auqat Sci 48: 888-897.
  7. Dang HT, Lee HJ, Yoo ES, Shinde PB, Lee YM, Hong J, Kim DK, Jung JH. 2008. Anti-inflammatory constituents of the red alga Gracilaria verrucosa and their synthetic analogues. J Nat Prod 71: 232-240. https://doi.org/10.1021/np070452q
  8. Kim SK, Wijesekara I. 2010. Development and biological activities of marine-derived bioactive peptides: A review. J Funct Foods 2: 1-9. https://doi.org/10.1016/j.jff.2010.01.003
  9. Jeong DH, Kim KB, Kim MJ, Kang BK, Ahn DH. 2014. Anti-inflammatory activity of methanol extract and n-hexane fraction mojabanchromanol b from Myagropsis myagroides. Life Sci 114: 12-19. https://doi.org/10.1016/j.lfs.2014.07.036
  10. Lee DS, Park WS, Heo SJ, Cha SH, Kim D, Jeon YJ, Park SG, Seo SK, Choi JS, Park SJ, Shim EB, Choi IW, Jung WK. 2011. Polyopes affinis alleviates airway inflammation in a murine model of allergic asthma. J Biosci 36: 869-877. https://doi.org/10.1007/s12038-011-9152-8
  11. Na HJ, Moon PD, Lee HJ, Kim HR, Chae HJ, Shin T, Seo Y, Hong SH, Kim HM. 2005. Regulatory effect of atopic allergic reaction by Carpopeltis affinis. J Ethnopharmacol 101: 43-48. https://doi.org/10.1016/j.jep.2005.03.026
  12. Heo SJ, Cha SH, Lee KW, Jeon YJ. 2006. Antioxidant activities of red algae from Jeju Island. Algae 21: 149-156. https://doi.org/10.4490/ALGAE.2006.21.1.149
  13. Hyun YJ, Piao MJ, Kim KC, Zheng J, Yao CW, Cha JW, Kang HK, Yoo ES, Koh YS, Lee NH, Ko MH, Hyun JW. 2014. Photoprotective effect of a Polyopes affinis (Harvey) Kawaguchi and Wang (Halymeniaceae)-derived ethanol extract on human keratinocytes. Trop J Pharm Res 13: 863-871. https://doi.org/10.4314/tjpr.v13i6.6
  14. Kim DW, Chi YS, Son KH, Chang HW, Kim JS, Kang SS, Kim HP. 2002. Effects of sophoraflavanone G, a prenylated flavonoid from Sophora flavescens, on cyclooxygenase-2 and in vivo inflammatory response. Arch Pharm Res 25: 329-335. https://doi.org/10.1007/BF02976635
  15. Saraiva RA, Araruna MK, Oliveira RC, Menezes KD, Leite GO, Kerntopf MR, Costa JG, Rocha JB, Tome AR, Campos AR, Menezes IR. 2011. Topical anti-inflammatory effect of Caryocar coriaceum Wittm. (Caryocaraceae) fruit pulp fixed oil on mice ear edema induced by different irritant agents. J Ethnopharmacol 136: 504-510. https://doi.org/10.1016/j.jep.2010.07.002
  16. Lee ST, Jeong YR, Ha MH, Kim SH, Byun MW, Jo SK. 2000. Induction of nitric oxide and TNF-${\alpha}$ by herbal plant extracts in mouse macrophages. J Korean Soc Food Sci Nutr 29: 342-348.
  17. Laemmli UK. 1970. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 227: 680-685. https://doi.org/10.1038/227680a0
  18. Towbin H, Staehelin T, Gordon J. 1979. Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. Proc Natl Acad Sci U S A 76: 4350-4354. https://doi.org/10.1073/pnas.76.9.4350
  19. 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
  20. Mu MM, Chakravortty D, Sugiyama T, Koide N, Takahashi K, Mori I, Yoshida T, Yokochi T. 2001. The inhibitory action of quercetin on lipopolysaccharide-induced nitric oxide production in RAW 264.7 macrophage cells. J Endotoxin Res 7: 431-438. https://doi.org/10.1177/09680519010070060601
  21. Dubois RN, Abramson SB, Crofford L, Gupta RA, Simon LS, Van De Putte LB, Lipsky PE. 1998. Cyclooxygenase in biology and disease. FASEB J 12: 1063-1073. https://doi.org/10.1096/fasebj.12.12.1063
  22. Perkins DJ, Kniss DA. 1999. Blockade of nitric oxide formation down-regulates cyclooxygenase-2 and decreases PGE2 biosynthesis in macrophages. J Leukoc Biol 65: 792-799. https://doi.org/10.1002/jlb.65.6.792
  23. Zhang JM, An J. 2009. Cytokines, inflammation and pain. Int Anesthesiol Clin 5: 27-37.
  24. Aggarwal BB, Natarajan K. 1996. Tumor necrosis factors: developments during the last decade. Eur Cytokine Netw 7: 93-124.
  25. Kim EY, Moudgil KD. 2008. Regulation of autoimmune inflammation by pro-inflammatory cytokines. Immunol Lett 120: 1-5. https://doi.org/10.1016/j.imlet.2008.07.008
  26. Van Q, Nayak BN, Reimer M, Jones PJ, Fulcher RG, Rempel CB. 2009. Anti-inflammatory effect of Inonotus obliquus, Polygala senega L., and Viburnum trilobum in a cell screening assay. J Ethnopharmacol 125: 487-493. https://doi.org/10.1016/j.jep.2009.06.026
  27. Nam NH. 2006. Naturally occurring NF-${\kappa}B$ inhibitors. Mini Rev Med Chem 6: 945-951. https://doi.org/10.2174/138955706777934937
  28. Johnson GL, Lapadat R. 2002. Mitogen-activated protein kinase pathways mediated by ERK, JNK, and p38 protein kinases. Science 298: 1911-1912. https://doi.org/10.1126/science.1072682
  29. Satyam SM, Bairy KL, Musharraf S, Fernandes DL. 2014. Inhibition of croton oil-induced oedema in rat ear skin by topical nicotinamide gel. Pharmacologyonline 3: 22-25.

Cited by

  1. The Functional Effects on Anti-oxidant and Anti-inflammation of Veronica persica Poir. Extracts vol.26, pp.4, 2018, https://doi.org/10.11625/KJOA.2018.26.4.661
  2. 참까막살 에탄올 추출물이 B16F10 흑색종 세포에서의 멜라닌합성에 미치는 영향연구 vol.29, pp.9, 2019, https://doi.org/10.5352/jls.2019.29.9.972