Korean Journal of Food Science and Technology (한국식품과학회지)

Korean Society of Food Science and Technology (한국식품과학회)
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Modulation of arachidonic acid metabolism and inflammatory process in macrophages by different solvent fractions of Glasswort (Salicornia herbacea L.) extract

큰포식세포에서 퉁퉁마디 추출물의 아라키돈산 대사효소조절 및 항염증 활성

  • Kang, Smee (Division of Applied Food System, College of Natural Science, Seoul Women's University) ;
  • Choi, YooMi (Division of Applied Food System, College of Natural Science, Seoul Women's University) ;
  • Hong, Jungil (Division of Applied Food System, College of Natural Science, Seoul Women's University)
  • 강스미 (서울여자대학교 자연과학대학 식품응용시스템학부) ;
  • 최유미 (서울여자대학교 자연과학대학 식품응용시스템학부) ;
  • 홍정일 (서울여자대학교 자연과학대학 식품응용시스템학부)
  • Received : 2018.09.13
  • Accepted : 2018.10.30
  • Published : 2018.12.31
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Abstract

Glasswort has attracted an attention because of its interesting physiological actions. In this study, the effects of glasswort on inflammatory events including nitric oxide (NO) synthesis and arachidonic acid metabolism in cultured RAW264.7 macrophages were investigated. A series of solvent fractions, including fractions of hexane (Fr.H), ethyl ether (Fr.E), ethyl acetate, butanol, and water, were prepared from a 70% methanol extract of glasswort. Among the fractions, Fr.E showed the strongest inhibition of NO synthesis and inducible NO synthase (iNOS) expression in lipopolysaccharide (LPS)-stimulated macrophages. At a concentration of $80{\mu}g/mL$, Fr.E decreased the NO and iNOS levels by 73 and 77%, respectively, after 24 h. Fr.E showed the most potent inhibitory effects on the expressions of cytosolic phospholipase $A_2$ and cyclooxygenase-2 with $IC_{50}$ values of 33.4 and $27.9{\mu}g/mL$, respectively. Fr.H and Fr.E also significantly inhibited 5-lipoxygenase expression in LPS-stimulated macrophages. These results suggest that the hydrophobic fractions of glasswort possess anti-inflammatory activities through modulating the arachidonic acid metabolism and NO synthesis.

퉁퉁마디는 식용 염생식물로서 이에 대한 유용 기능성 탐색 및 생리활성 평가에 대한 연구가 지속적으로 진행되고 있다. 본 연구에서는 퉁퉁마디 70% 메탄올 추출물을 극성에 따라 분획하여 얻은 Fr.H, Fr.E, Fr.EA, Fr.B 및 Fr.W의 5분획의 NO제거 및 iNOS 발현, 아라키돈산 대사에 관련된 효소 $cPLA_2$, COX-2, 5-LOX 등의 발현과 활성화에 대한 효과를 분석하여 항염작용과 메커니즘을 검토하였다. 이 중 Fr.EA가 가장 높은 폴리페놀 및 플라보노이드 성분 함량을 나타내었고 nitrite/아질산의 제거에 있어서도 가장 뛰어난 활성을 보였다. 하지만 LPS로 자극한 RAW264.7 큰포식세포 배양계에서는 Fr.E가 가장 우수한 NO 제거활성과 iNOS발현억제 활성을 나타내었고 이어 Fr.H와 Fr.EA의 활성 순을 나타냈다. Fr.E는 또한 LPS로 자극한 RAW264.7 배양 세포계에서 $cPLA_2$와 COX-2의 발현억제에 가장 큰 효과를 나타내었으며 이들의 억제를 위한 $IC_{50}$는 각각 33.4과 $27.9{\mu}g/mL$로 나타났다. Fr.E는 $cPLA_2$의 활성화에 중요한 영향을 미치는 ERK1/2의 인산화도 농도의존적으로 저해하였다. Fr.H와 Fr.EA도 $80{\mu}g/mL$ 이하 농도에서 iNOS와 아라키돈산 대사효소들의 발현을 농도의존적으로 억제하였다. 하지만 가장 극성 분획인 Fr.W는 모든 활성평가 시스템에서 거의 효과를 나타내지 않았다. 본 연구는 퉁퉁마디가 iNOS와 아라키돈산 대사효소계를 효과적으로 억제하여 항염증작용을 할 수 있다는 것을 보고하고 있으며, 특히 Fr.E와 Fr.H와 같은 소수성 분획들이 우수한 활성을 나타내어 향후 이를 타깃으로 하는 관련 기능성 소재로서의 활용이 기대된다.

Keywords

SPGHB5_2018_v50n6_671_f0001.png 이미지

Fig. 1. Contents of total polyphenols and flavonoids in the fractions from glasswort (A) and their nitrite scavenging activities (B).

SPGHB5_2018_v50n6_671_f0002.png 이미지

Fig. 2. Effects of the glasswort fractions on cell viability and NO production in RAW264.7 cells.

SPGHB5_2018_v50n6_671_f0003.png 이미지

Fig. 3. Effects of the fractions from glasswort on the expressions of iNOS in LPS-stimulated RAW264.7 macrophages.

SPGHB5_2018_v50n6_671_f0004.png 이미지

Fig. 4. Effects of the fractions from glasswort on the expressions of cPLA2 in LPS-stimulated RAW264.7 macrophages.

SPGHB5_2018_v50n6_671_f0005.png 이미지

Fig. 5. Effects of Fr.E from glasswort on the level of ERK and p-ERK in LPS-stimulated RAW264.7 cells.

SPGHB5_2018_v50n6_671_f0006.png 이미지

Fig. 6. Effects of the fractions from glasswort on the expressions of COX-2 and 5-LOX in LPS-stimulated RAW264.7 macrophages.

References

  1. Bogdan C. Nitric oxide and the immune response. Nat. Immunol. 2: 907-916 (2001) https://doi.org/10.1038/ni1001-907
  2. Cha JY, Jeong JJ, Kim YT, Seo WS, Yang HJ, Kim JS, Lee YS. Detection of chemical characteristics in Hamcho (Salicornia herbacea L.) according to harvest periods. J. Life Sci. 16: 683-690 (2006) https://doi.org/10.5352/JLS.2006.16.4.683
  3. Ferrucci L, Fabbri E. Inflammageing: chronic inflammation in ageing, cardiovascular disease, and frailty. Nat. Rev. Cardiol. 15: 505-522 (2018) https://doi.org/10.1038/s41569-018-0064-2
  4. Gonzalez-Periz A, Claria J. New approaches to the modulation of the cyclooxygenase-2 and 5-lipoxygenase pathways. Curr. Top. Med. Chem. 7: 297-309 (2007) https://doi.org/10.2174/156802607779941378
  5. Gray JI, Dugan LR. Inhibition of N-nitrosamine formation in model food systems. J. Food Sci. 40: 981-984 (1975) https://doi.org/10.1111/j.1365-2621.1975.tb02248.x
  6. Greene ER, Huang S, Serhan CN, Panigrahy D. Regulation of inflammation in cancer by eicosanoids. Prostag. Oth. Lipid M. 96: 27-36 (2011) https://doi.org/10.1016/j.prostaglandins.2011.08.004
  7. Grivennikov SI, Greten FR, Karin M. Immunity, inflammation, and cancer. Cell 140:883-899 (2010) https://doi.org/10.1016/j.cell.2010.01.025
  8. Guzik TJ, Korbut R, Adamek-Guzik T. Nitric oxide and superoxide in inflammation and immune regulation. J. Physiol. Pharmacol. 54: 469-487 (2003)
  9. Hamminga EA, Thio HB. Chronic inflammation in psoriasis and obesity: Implications for therapy. Med. Hypotheses 67: 768-773 (2006) https://doi.org/10.1016/j.mehy.2005.11.050
  10. Hiller G, Sundler R. Activation of arachidonate release and cytosolic phospholipase $A_2$ via extracellular signal-regulated kinase and p38 mitogen-activated protein kinase in macrophages stimulated by bacteria or zymosan. Cell. Signal. 11: 863-869 (1999) https://doi.org/10.1016/S0898-6568(99)00058-3
  11. Hong J, Sang S, Park HJ, Kwon SJ, Suh N, Huang MT, Ho CT, Yang CS. Modulation of arachidonic acid metabolism and nitric oxide synthesis by garcinol and its derivatives. Carcinogenesis 27: 278-286 (2006) https://doi.org/10.1093/carcin/bgi208
  12. Im SA, Kim GW, Lee CK. Immunomodulation activity of Salicornia herbacea L. components. Nat. Prod. Sci. 9: 791-800 (2006)
  13. Jo YC, Ahn JH, Chon SM, Lee KS, Bae TJ, Kang DS. Studies on pharmacological effects of glasswort (Salicornia herbacea L.). Korean J. Medicinal Crop Sci. 10: 93-99 (2002)
  14. Kang S, Hong J. Antioxidant activities, production of reactive oxygen species, and cytotoxic properties of fractions from aerial parts of glasswort (Salicornia herbacea L.). Korean J. Food Sci. Technol. 48: 574-581 (2016) https://doi.org/10.9721/KJFST.2016.48.6.574
  15. Kim YA, Kong CS, Um YR, Lim SY, Yea SS, Seo Y. Evaluation of Salicornia herbacea as a potential antioxidant and anti-inflammatory agent. J. Med. Food 12: 661-668 (2009) https://doi.org/10.1089/jmf.2008.1072
  16. Lee NH. Antioxidant properties and neuro-protective effect of part cnidium officinale malino. MS thesis, University of Seoul Women's, Seoul, Korea (2009)
  17. Lee CH, Kim IH, Kim YE, O SW, Lee HJ. Determination of Betaine from Salicornia herbacea L. J. Korean Soc. Food Sci. Nutr. 33: 1584-1587 (2004a) https://doi.org/10.3746/jkfn.2004.33.9.1584
  18. Lee YS, Lee HS, Shin KH, Kim BK, Lee S. Constituents of the halophyte Salicornia herbacea. Arch. Pharm. Res. 27: 1034-1036 (2004b) https://doi.org/10.1007/BF02975427
  19. Lee WM, Sung HJ, Song JC, Cho JY, Park HJ, Kim S, Rhee MH. Effects of solvent-extracted fractions from Salicornia herbacea on anti-oxidative activity and lipopolysaccharide-induced NO production in murine macrophage RAW264.7 cells. J. Exp. Biomed. Sci. 13: 161-168 (2007)
  20. Leslie CC. Properties and regulation of cytosolic phospholipase $A_2$. J. Biol. Chem. 272: 16709-16712 (1997) https://doi.org/10.1074/jbc.272.27.16709
  21. Leslie CC. Cytosolic phospholipase $A_2$: physiological function and role in disease. J Lipid Res. 56: 1386-402 (2015) https://doi.org/10.1194/jlr.R057588
  22. Lim CW, Park HY, Kim YK, Lee DS, Song KC. Contents of inogganic metals from halophyte and shellfish living in the beach sediment. J. Korean Soc. Appl. Biol. Chem. 50: 121-126 (2007)
  23. Lundberg JO, Weitzberg E, Gladwin MT. The nitrate-nitrite-nitric oxide pathway in physiology and therapeutics. Nat. Rev. Drug Discov. 7: 156-167 (2008) https://doi.org/10.1038/nrd2466
  24. Macarthur M, Hold GL, El-Omar EM. Inflammation and Cancer II. Role of chronic inflammation and cytokine gene polymorphisms in the pathogenesis of gastrointestinal malignancy. Am. J. Physiol.-Gastro. L. 286: 515-520 (2004) https://doi.org/10.1152/ajpgi.00475.2003
  25. Marletta MA, Yoon PS, Iyengar R, Leaf CD, Wishnok JS. Macrophage oxidation of L-arginine to nitrite and nitrate: nitric oxide is an intermediate. Biochemistry 27: 8706-8711 (1988) https://doi.org/10.1021/bi00424a003
  26. Nagy G, Clark JM, Buzas EI, Gorman CL, Cope AP. Nitric oxide, chronic inflammation and autoimmunity. Immunol. Lett. 111: 1-5 (2007) https://doi.org/10.1016/j.imlet.2007.04.013
  27. Ricciotti E, FitzGerald GA. Prostaglandins and inflammation. Arterioscl. Throm. Vas. 31: 986-1000 (2011) https://doi.org/10.1161/ATVBAHA.110.207449
  28. Romano M, Claria J. Cyclooxygenase-2 and 5-lipoxygenase converging functions on cell proliferation and tumor angiogenesis: implications for cancer therapy. FASEB J. 17: 1986-1995 (2003) https://doi.org/10.1096/fj.03-0053rev
  29. Rossol M, Heine H, Meusch U, Quandt D, Klein C, Sweet MJ, Hauschildt S. LPS-induced cytokine production in human monocytes and macrophages. Crit. Rev. Immunol. 31: 379-446 (2011). https://doi.org/10.1615/CritRevImmunol.v31.i5.20
  30. Shin KS, Boo HO, Jeon MW, Ko JY. Chemical components of native plant, Salicornia herbacea L.. Korean J. Plant. Res. 15: 216-220 (2002)
  31. Steele VE, Holmes CA, Hawk ET, Kopelovich L, Lubet RA, Crowell JA, Sigman CC, Kelloff GJ. Lipoxygenase inhibitors as potential cancer chemopreventives. Cancer Epidem. Biomar. 8: 467-483 (1999)
  32. Steinhilber D, Hofmann B. Recent advances in the search for novel 5-lipoxygenase inhibitors. Basic Clin. Pharmacol. 114: 70-77 (2014) https://doi.org/10.1111/bcpt.12114
  33. Swain, T. and Hillis, W.E. The phenolic constituents of Prunus domestica. I. - The quantitative analysis of phenolic constituents. J. Sci. Food Agr. 10: 63-68 (1959) https://doi.org/10.1002/jsfa.2740100110
  34. Wang D, Dubois RN. Prostaglandins and cancer. Gut 55: 115-122 (2006) https://doi.org/10.1136/gut.2004.047100
  35. Williams CS, Mann M, DuBois RN. The role of cyclooxygenases in inflammation, cancer, and development. Oncogene 18: 7908-7916 (1999) https://doi.org/10.1038/sj.onc.1203286