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The pepsinolytic hydrolysate from Johnius belengerii frame inhibited LPS-stimulated production of pro-inflammatory mediators via the inactivating of JNK and NF-κB pathways in RAW 264.7 macrophages

  • Heo, Seong-Yeong (Department of Biomedical Engineering and Center for Marine-Integrated Biomedical Technology (BK21 Plus), Pukyong National University) ;
  • Ko, Seok-Chun (Marine-Integrated Bionics Research Center, Pukyong National University) ;
  • Jung, Won-Kyo (Department of Biomedical Engineering and Center for Marine-Integrated Biomedical Technology (BK21 Plus), Pukyong National University)
  • Received : 2018.01.20
  • Accepted : 2018.02.20
  • Published : 2018.05.31

Abstract

The objective of this study was to investigate the anti-inflammatory effects of the pepsinolytic hydrolysate from the fish frame, Johnius belengerii, on lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. The J. belengerii frame hydrolysate (JFH) significantly suppressed nitric oxide (NO) secretion on LPS-stimulated RAW264.7 macrophages. Moreover, the JFH markedly inhibited the levels of protein and mRNA expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Furthermore, the LPS-stimulated mRNA expression of pro-inflammatory cytokines, including tumor necrosis factor $(TNF)-{\alpha}$, interleukin $(IL)-1{\beta}$, and IL-6 was downregulated when cells were cultured with the JFH. The JFH significantly reduced the phosphorylation of c-Jun N-terminal kinase (JNK) and the translocation of nuclear factor-kappa B ($NF-{\kappa}B$) in macrophages. As the result, the JFH has the potential anti-inflammatory activity via blocking the JNK and $NF-{\kappa}B$ signal pathways.

Keywords

References

  1. Ahn CB, Cho YS, Je JY. Purification and anti-inflammatory action of tripeptide from salmon pectoral fin byproduct protein hydrolysate. Food Chem. 2015;168:151-6. https://doi.org/10.1016/j.foodchem.2014.05.112
  2. Ahn CB, Je JY, Cho YS. Antioxidant and anti-inflammatory peptide fraction from salmon byproduct protein hydrolysates by peptic hydrolysis. Food Res Int. 2012;49:92-8. https://doi.org/10.1016/j.foodres.2012.08.002
  3. Bonnefous C, Payne JE, Roppe J, Zhuang H, Chen X, Symons KT, Nguyen PM, Sablad M, Rozenkrants N, Zhang Y, Wang L, Severance D, Walsh JP, Yazdani N, Shiau AK, Noble SA, Rix P, Rao TS, Hassig CA, Smith ND. Discovery of inducible nitric oxide synthase (iNOS) inhibitor development candidate KD7332, part 1: identification of a novel, potent, and selective series of quinolinone iNOS dimerization inhibitors that rae orally active in roden pain models. J Med Chem. 2009;52:3047-62. https://doi.org/10.1021/jm900173b
  4. Cattaneo F, Sayago JE, Alberto MR, Zampini IC, Ordonez RM, Chamorro V, Pazos A, Isla MI. Anti-inflammatory and antioxidant activities, functional properties and mutagenicity studies of protein and protein hydrolysate obtained from Prosopis alba seed flour. Food Chem. 2014;161:391-9. https://doi.org/10.1016/j.foodchem.2014.04.003
  5. Chalamaiah M, Dinesh Kumar B, Hemalatha R, Jyothirmayi T. Fish protein hydrolysates: proximate composition, amino acid composition, antioxidant activities and applications: a review. Food Chem. 2012;135:3020-38. https://doi.org/10.1016/j.foodchem.2012.06.100
  6. Choi YY, Kim MH, Han JM, Hong J, Lee TH, Kim SH, Yang WM. The antiinflammatory potential of Cortex Phellodendron in vivo and in vitro: downregulation of NO and iNOS through suppression of $NF-{\kappa}B$ and MAPK activation. Int Immunopharmacol. 2014;19:214-20. https://doi.org/10.1016/j.intimp.2014.01.020
  7. del Carmen M-LM, del Mar YM, Alcaide-Hidalgo JM, Millan F, Pedroche J. Lupine protein hydrolysates inhibit enzymes involved in the inflammatory pathway. Food Chem. 2014;151:141-7. https://doi.org/10.1016/j.foodchem.2013.11.053
  8. Dennler S, Prunier C, Ferrand N, Gauthier JM, Atfi A. c-Jun inhibits transforming growth factor ${\beta}$-mediated transcription by repressing Smad3 transcriptional activity. J Biol Chem. 2000;275:28858-65. https://doi.org/10.1074/jbc.M910358199
  9. Halldorsdottir SM, Sveinsdottir H, Freysdottir J, Kristinsson HG. Oxidative processes during enzymatic hydrolysis of cod protein and their influence on antioxidant and immunomodulating ability. Food Chem. 2014;142:201-9. https://doi.org/10.1016/j.foodchem.2013.07.053
  10. Holen E, He J, Araujo P, Seliussen J, Espe M. Hydrolyzed fish proteins modulates both inflammatory and antioxidant gene expression as well as protein expression in a co culture model of liver and head kidney cells isolated from Atlantic salmon (Salmo salar). Fish Shellfish Immun. 2016;54:22-9. https://doi.org/10.1016/j.fsi.2016.03.030
  11. Hwang JW, Lee SJ, Kim YS, Kim EK, Ahn CB, Jeon YJ, Moon SH, Jeon BT, Park PJ. Purification and characterization of a novel peptide with inhibitory effects on colitis induced mice by dextran sulfate sodium from enzymatic hydrolysates of Crassostrea gigas. Fish Shellfish Immun. 2012;33:993-9. https://doi.org/10.1016/j.fsi.2012.08.017
  12. Ishihara K, Hirano T. IL-6 in autoimmune disease and chronic inflammatory proliferative disease. Cytokine Growth Factor Rev. 2002;13:357-68. https://doi.org/10.1016/S1359-6101(02)00027-8
  13. Jeong DH, Kim MJ, Kang BK, Ahn DH. Skipjack tuna (Katsuwonus pelamis) eyeball oil exerts an anti-inflammatory effect by inhibiting $NF-{\kappa}B$ and MAPK activation in LPS-induced RAW 264.7 cells and croton oil-treated mice. Int Immunopharmacol. 2016;40:50-6. https://doi.org/10.1016/j.intimp.2016.07.005
  14. Jovanovic DV, Di Battista JA, Martel-Pelletier J, Jolicoeur FC, He Y, Zhang M, Mineau F, Pelletier JP. IL-17 stimulates the production and expression of proinflammatory cytokines, $IL-{\beta}$ and $TNF-{\alpha}$, by human macrophages. J Immunol. 1998;160:3513-21.
  15. Jung WK, Kim SK. Calcium-binding peptide derived from pepsinolytic hydrolysates of hoki (Johnius belengerii) frame. Eur Food Res Technol. 2007;224:763-7. https://doi.org/10.1007/s00217-006-0371-4
  16. Kim AR, Lee B, Joung EJ, Gwon WG, Utsuki T, Kim NG, Kim HR. 6,6′-bieckol suppresses inflammatory responses by down-regulating nuclear $factor-{\kappa}B$ activation via Akt, JNK, and p38 MAPK in LPS-stimulated microglial cells. Immunopharm Immunotoxicol. 2016;38:244-52. https://doi.org/10.3109/08923973.2016.1173060
  17. Kim EK, Kim YS, Hwang JW, Kang SH, Choi DK, Lee KH, Lee JS, Moon SH, Jeon BT, Park PJ. Purification of a novel nitric oxide inhibitory peptide derived from enzymatic hydrolysates of Mytilus coruscus. Fish Shellfish Immunol. 2013;34:1416-20. https://doi.org/10.1016/j.fsi.2013.02.023
  18. Kim SY, Je JY, Kim SK. Purification and characterization of antioxidant peptide from hoki (Johnius belengerii) frame protein by gastrointestinal digestion. J Nutr Biochem. 2007;18:31-8. https://doi.org/10.1016/j.jnutbio.2006.02.006
  19. Kim YK, Jeong EJ, Lee MS, Yoon NY, Yoon HD, Kim JI, Kim HR. Ethanolic extract of Chondria crassicaulis inhibits the expression of inducible nitric oxide synthase and cyclooxygenase-2 in LPS-stimulated RAW 264.7 macrophages. Fish Aquat Sci. 2011;14:275-82.
  20. Kim YS, Ahn CB, Je JY. Anti-inflammatory action of high molecular weight Mytilus edulis hydrolysates fraction in LPS-induced RAW264. 7 macrophage via $NF-{\kappa}B$ and MAPK pathways. Food Chem. 2016;202:9-14. https://doi.org/10.1016/j.foodchem.2016.01.114
  21. Ko SC, Jeon YJ. Anti-inflammatory effect of enzymatic hydrolysates from Styela clava flesh tissue in lipopolysaccharide-stimulated RAW 264.7 macrophages and in vivo zebrafish model. Nutr Res Pract. 2015;9:219-26. https://doi.org/10.4162/nrp.2015.9.3.219
  22. Kobayashi EH, Suzuki T, Funayama R, Nagashima T, Hayashi M, Sekine H, Tanaka N, Moriguchi T, Motohashi H, Nakayama K, Yamamoto M. Nrf2 suppresses macrophage inflammatory response by blocking proinflammatory cytokine transcription. Nat Commun. 2016;7:11624. https://doi.org/10.1038/ncomms11624
  23. Lee SJ, Kim EK, Kim YS, Hwang JW, Lee KH, Choi DK, Kang H, Moon SH, Jeon BT, Park PJ. Purification and characterization of a nitric oxide inhibitory peptide from Ruditapes philippinarum. Food Che Toxicol. 2012;50:1660-6. https://doi.org/10.1016/j.fct.2012.02.021
  24. Ligumsky M, Simon P, Karmeli F, Rachmilewitz D. Role of interleukin 1 in inflammatory bowel disease-enhanced production during active disease. Gut. 1990;31:686-9. https://doi.org/10.1136/gut.31.6.686
  25. Morales-Medina R, Tamm F, Guadix AM, Guadix EM, Drusch S. Functional and antioxidant properties of hydrolysates of sardine (S. pilchardus) and horse mackerel (T. mediterraneus) for the microencapsulation of fish oil by spraydrying. Food Chem. 2016;194:1208-16. https://doi.org/10.1016/j.foodchem.2015.08.122
  26. Ngo DH, Kang KH, Ryu B, Vo TS, Jung WK, Byun HG, Kim SK. Angiotensin-I converting enzyme inhibitory peptides from antihypertensive skate (Okamejei kenojei) skin gelatin hydrolysate in spontaneously hypertensive rats. Food Chem. 2015;174:37-43. https://doi.org/10.1016/j.foodchem.2014.11.013
  27. Nguyen MHT, Qian ZJ, Jung WK. Beneficial effect of abalone intestine gastrointestinal digests on osteoblastic MG-63 cell differentiation. J Aquat Food Prod Technol. 2014;23:436-46. https://doi.org/10.1080/10498850.2012.721874
  28. Nguyen VT, Qian ZJ, Jung WK. Abalone Haliotis discus hannai intestine digests with different molecule weights inhibit MMP-2 and MMP-9 expression in human fibrosarcoma cells. Fish Aquat Sci. 2012;15:137-43.
  29. Oh GW, Ko SC, Lee DH, Heo SJ, Jung WK. Biological activities and biomedical potential of sea cucumber (Stichopus japonicus): a review. Fish Aquat Sci. 2017;20:28. https://doi.org/10.1186/s41240-017-0071-y
  30. Qian ZJ, Kim SA, Lee JS, Kim HJ, Choi IW, Jung WK. The antioxidant and antiinflammatory effects of abalone intestine digest, Haliotis discus hannai in RAW 264.7 macrophages. Biotechnol Bioprocess Eng. 2012;17:475-84. https://doi.org/10.1007/s12257-011-0544-2
  31. Reuter S, Gupta SC, Chaturvedi MM, Aggarwal BB. Oxidative stress, inflammation, and cancer: how are they linked? Free Radical Bio Med. 2010;49:1603-16. https://doi.org/10.1016/j.freeradbiomed.2010.09.006
  32. Ryu B, Choi IW, Qian ZJ, Heo SJ, Kang DH, Oh C, Jeon YJ, Jang CH, Park WS, Kang KH. Anti-inflammatory effect of polyphenol-rich extract from the red alga Callophyllis japonica in lipopolysaccharide-induced RAW 264.7 macrophages. Algae. 2014;29:343. https://doi.org/10.4490/algae.2014.29.4.343
  33. Segovia J, Mgbemena V, Chang TH, Bose S. Kruppel-like factor 6 and inducible nitric oxide synthase regulates apoptosis during respiratory syncytial virus infection (P6198). J Immunol. 2013;190:189.14.
  34. Sung NY, Jung PM, Yoon M, Kim JS, Ji C, Jeong HG, Lee JW, Kim JH. Antiinflammatory effect of sweetfish-derived protein and its enzymatic hydrolysate on LPS-induced RAW 264. 7 cells via inhibition of $NF-{\kappa}B$ transcription. Fish Sci. 2012;78:381-90. https://doi.org/10.1007/s12562-011-0461-5
  35. Tak PP, Firestein GS. $NF-{\kappa}B$: a key role in inflammatory diseases. J Clin Invest. 2001;107:7-11. https://doi.org/10.1172/JCI11830
  36. Wehbi VL, Tasken K. Molecular mechanisms for cAMP mediated immunoregulation in T cells-role of anchored protein kinase A signaling units. Front in Immunol. 2016;7:222.
  37. Yeom M, Kim JH, Min JH, Hwang MK, Jung HS, Sohn Y. Xanthii fructus inhibits inflammatory responses in LPS-stimulated RAW 264.7 macrophages through suppressing $NF-{\kappa}B$ and JNK/p38 MAPK. J Ethnopharmacol. 2015;176:394-401. https://doi.org/10.1016/j.jep.2015.11.020
  38. Yoon HD, Jeong EJ, Choi JW, Lee MS, Park M, Yoon NY, Kim YK, Cho DM, Kim JI, Kim HR. Anti-inflammatory effects of ethanolic extracts from Codium fragile on LPS-stimulated RAW 264.7 macrophages via nuclear factor kappaB inactivation. Fish Aquat Sci. 2011;14:267-74.
  39. Yuan Z, Matias FB, Wu J, Liang Z, Sun Z. Koumine attenuates lipopolysaccaridestimulated inflammation in RAW264. 7 macrophages, coincidentally associated with inhibition of $NF-{\kappa}B$, ERK and p38 pathways. Int J Mol Sci. 2016;17:430. https://doi.org/10.3390/ijms17030430

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