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Characterization of antioxidant and anti-inflammatory activities of bioactive fractions recovered from a glucose−lysine Maillard reaction model system

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Abstract

A glucose−lysine (Glu−Lys) Maillard reaction mixture heated at 121°C for 60 min was processed by ultrafiltration, ethyl acetate extraction, and semi-preparative HPLC to recover a bioactive fraction, termed F3. F3, characterized by spectral analysis to contain three distinct components, inhibited NO and IL-8 by 70 and 61%, respectively, at a concentration of 50 μg/ml in inflamed Caco-2 cells induced by IFN-γ and phorbol 12-myristate 13-acetate (PMA). F3 significantly (P < 0.05) down-regulated several genes involved in nuclear factor kappa B (NF-κB) signaling pathway. These genes included the cytokine receptors, TNFRSF10A and TNFRSF10B; receptor-associated proteins, IRAK2 and TICAM1; the inhibitor κB kinase, IKBKE; the NF-κB inhibitor, NFKBIA; and the NF-κB subunits, REL, RELA, and RELB. F3 also down-regulated the NF-κB responsive genes IL-8, NOS2, and ICAM1, attenuated the gene expression of peroxidases such as DUOX1 and DUOX2, and relieved the down-regulated GCFHR that are involved in the biosynthesis of NO and TROAP, a gene suppressed by NO. The anti-inflammatory activity of F3 was mediated through multiple processes that included regulation of gene expressions involved in NF-κB signaling, the inhibition of IL-8 and iNOS translation, a decrease in NO synthesis and attenuating oxidative stress in inflamed Caco-2 cells. Our results show that MRP components have the potential to suppress inflammation in IFN-γ and PMA-induced Caco-2 cells.

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Abbreviations

3-MCP:

3-Methyl-1,2-cyclopentanedione

AAPH:

2,2′-Azobis(2-amidinopropane) hydrochloride

AGEs:

Advanced glycation end products

BH4:

Tetrahydrobiopterin

COX-2:

Cyclooxygenase 2

ddH2O:

Distilled deionised water

DUOX1:

Dual oxidase 1

DUOX2:

Dual oxidase 2

FI:

Fluorescence intensity

GCHFR:

GTP cyclohydrolase I feedback regulator

GFRP:

GTP cyclohydrolase feedback regulator protein

Glu:

Glucose

GTP:

Guanosine triphosphate

HBSS:

Hank’s buffered salt solution

IBD:

Inflammatory bowel diseases

ICAM1:

Intercellular adhesion molecule 1

IECs:

Intestinal epithelial cells

IKBKE:

Inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase epsilon

IKK:

Inhibitor κB kinase

iNOS:

Inducible nitric oxide synthase

IRAK2:

Interleukin-1 receptor-associated kinase 2

Lys:

Lysine

MEKK-1:

Mitogen-activated protein kinase 1

MEM:

Minimum Essential Medium

MR:

Maillard reaction

MRPs:

Maillard reaction products

MTT:

3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide

MW:

Molecular weight

NFKBIA:

Nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha

NIK:

NF-kB inducing kinase

NO:

Nitric oxide

ORACFL :

Oxygen radical absorbance capacity-fluorescein

PMA:

Phorbol 12-myristate 13-acetate

RAGE:

Receptor for AGEs

REL:

V-rel reticuloendotheliosis viral oncogene homolog (avian)

RELA:

V-rel reticuloendotheliosis viral oncogene homolog A (avian)

RELB:

V-rel reticuloendotheliosis viral oncogene homolog B

ROS:

Reactive oxygen species

TICAM1:

Toll-like receptor adaptor molecule 1

TNF-α:

Tumor necrosis factor alpha

TNFRSF10A:

Tumor necrosis factor receptor superfamily, member 10a

TNFRSF10B:

Tumor necrosis factor receptor superfamily, member 10b

TRAILR1:

TNF-related apoptosis-inducing ligand receptor 1

TRAILR2:

TNF-related apoptosis-inducing ligand receptor 2

TROAP:

Trophinin-associated protein

References

  1. Jing H, Kitts DD (2004) Antioxidant activity of sugar-lysine Maillard reaction products in cell free and cell culture systems. Arch Biochem Biophys 429:154–163

    Article  PubMed  CAS  Google Scholar 

  2. Chen XM, Kitts DD (2008) Antioxidant activity and chemical properties of crude and fractionated Maillard reaction products derived from four sugar-amino acid Maillard reaction model systems. Ann N Y Acad Sci 1126:220–224

    Article  PubMed  CAS  Google Scholar 

  3. Liu JH, Zhao SC, Tang J, Li ZJ, Zhong TY, Liu YW, Chen DY, Zhao MZ, Li YS, Gong XW, Deng P, Wang JH, Jiang Y (2009) Advanced glycation end products and lipopolysaccharide synergistically stimulate proinflammatory cytokine/chemokine production in endothelial cells via activation of both mitogen-activated protein kinases and nuclear factor-kappa B. FEBS J 276:4598–4606

    Article  PubMed  CAS  Google Scholar 

  4. Wu CH, Huang CM, Lin CH, Ho YS, Chen CM, Lee HM (2002) Advanced glycosylation end products induce NF-kappa B dependent NOS expression in RAW 264.7 cells. Mol Cell Endocrinol 194:9–17

    Article  PubMed  CAS  Google Scholar 

  5. Chavakis T, Bierhaus A, Nawroth PP (2004) RAGE (receptor for advanced glycation end products): a central player in the inflammatory response. Microbes Infect 6:1219–1225. doi:10.1016/j.micinf.2004.08.004

    Article  PubMed  CAS  Google Scholar 

  6. Franke S, Sommer M, Ruster C, Bondeva T, Marticke J, Hofmann G, Hein G, Wolf G (2009) Advanced glycation end products induce cell cycle arrest and proinflammatory changes in osteoarthritic fibroblast-like synovial cells. Arthritis Res Ther 11:R136–R154. doi:10.1186/ar2807

    Article  PubMed  Google Scholar 

  7. Deo P, Glenn JV, Powell LA, Stitt AW, Ames JM (2009) Upregulation of oxidative stress markers in human microvascular endothelial cells by complexes of serum albumin and digestion products of glycated casein. J Biochem Mol Toxicol 23:364–372. doi:10.1002/jbt.20301

    Article  PubMed  CAS  Google Scholar 

  8. Huang CY, Hung LF, Liang CC, Ho LJ (2009) COX-2 and iNOS are critical in advanced glycation end product-activated chondrocytes in vitro. Eur J Clin Invest 39:417–428. doi:10.1111/j.1365-2362.2009.02106.x

    Article  PubMed  CAS  Google Scholar 

  9. Bengmark S (2007) Advanced glycation and lipoxidation end products–amplifiers of inflammation: the role of food. J Parenter Enteral Nutr 31:430–440. doi:10.1177/0148607107031005430

    Article  CAS  Google Scholar 

  10. Buetler TM, Latado H, Baumeyer A, Delatour T (2008) Dicarbonyls stimulate cellular protection systems in primary rat hepatocytes and show anti-inflammatory properties. Ann N Y Acad Sci 1126:113–117

    Article  PubMed  CAS  Google Scholar 

  11. Chung JH, Choi SY, Kim JY, Kim DH, Lee JW, Choi JS, Chung HY (2007) 3-Methyl-1,2-cyclopentanedione down-regulates age-related NF-kappa B signaling cascade. J Agric Food Chem 55:6787–6792

    Article  PubMed  CAS  Google Scholar 

  12. Chen XM, Kitts DD (2011) Antioxidant and anti-inflammatory activities of Maillard reaction products isolated from sugar-amino acid model systems. J Agric Food Chem. doi:10.1021/jf2031583

  13. Jobin C, Sartor RB (2000) The I kappa B/NF-kappa B system: a key determinant of mucosalinflammation and protection. Am J Physiol Cell Physiol 278:C451–C462

    PubMed  CAS  Google Scholar 

  14. Lang A, Lahav M, Sakhnini E, Barshack I, Fidder HH, Avidan B, Bardan E, Hershkoviz R, Bar-Meir S, Chowers Y (2004) Allicin inhibits spontaneous and TNF-alpha induced secretion of proinflammatory cytokines and chemokines from intestinal epithelial cells. Clin Nutr 23:1199–1208. doi:10.1016/j.clnu.2004.03.011

    Article  PubMed  CAS  Google Scholar 

  15. Yamamoto K, Kushima R, Kisaki O, Fujiyama Y, Okabe H (2003) Combined effect of hydrogen peroxide induced oxidative stress and IL-1 alpha on IL-8 production in CaCo-2 cells (a human colon carcinoma cell line) and normal intestinal epithelial cells. Inflammation 27:123–128

    Article  PubMed  CAS  Google Scholar 

  16. Daig R, Andus T, Aschenbrenner E, Falk W, Scholmerich J, Gross V (1996) Increased interleukin 8 expression in the colon mucosa of patients with inflammatory bowel disease. Gut 38:216–222

    Article  PubMed  CAS  Google Scholar 

  17. Kimura H, Hokari R, Miura S, Shigematsu T, Hirokawa M, Akiba Y, Kurose I, Higuchi H, Fujimori H, Tsuzuki Y, Serizawa H, Ishii H (1998) Increased expression of an inducible isoform of nitric oxide synthase and the formation of peroxynitrite in colonic mucosa of patients with active ulcerative colitis. Gut 42:180–187

    Article  PubMed  CAS  Google Scholar 

  18. Chen XM, Kitts DD (2008) Determining conditions for nitric oxide synthesis in Caco-2 cells using Taguchi and factorial experimental designs. Anal Biochem 381:185–192. doi:10.1016/j.ab.2008.07.013

    Article  PubMed  CAS  Google Scholar 

  19. Son DO, Satsu H, Shimizu M (2005) Histidine inhibits oxidative stress- and TNF-alpha-induced interleukin-8 secretion in intestinal epithelial cells. FEBS Lett 579:4671–4677

    Article  PubMed  CAS  Google Scholar 

  20. Xie QW, Kashiwabara Y, Nathan C (1994) Role of transcription factor NF-kappa B/Rel in induction of nitric oxide synthase. J Biol Chem 269:4705–4708

    PubMed  CAS  Google Scholar 

  21. Jobin C, Sartor RB (2000) NF-kappaB signaling proteins as therapeutic targets for inflammatory bowel diseases. Inflamm Bowel Dis 6:206–213

    Article  PubMed  CAS  Google Scholar 

  22. Kitts DD, Hu C (2005) Biological and chemical assessment of antioxidant activity of sugar-lysine model Maillard reaction products. Ann N Y Acad Sci 1043:501–512. doi:10.1196/annals.1333.057

    Article  PubMed  CAS  Google Scholar 

  23. Jobin C, Haskill S, Mayer L, Panja A, Sartor RB (1997) Evidence for altered regulation of I kappa B alpha degradation in human colonic epithelial cells. J Immunol 158:226–234

    PubMed  CAS  Google Scholar 

  24. Sun SC, Ganchi PA, Ballard DW, Greene WC (1993) NF-kappa B controls expression of inhibitor I kappa B alpha: evidence for an inducible autoregulatory pathway. Science 259:1912–1915

    Article  PubMed  CAS  Google Scholar 

  25. Neurath MF, Becker C, Barbulescu K (1998) Role of NF-kappaB in immune and inflammatory responses in the gut. Gut 43:856–860

    Article  PubMed  CAS  Google Scholar 

  26. Jacobs MD, Harrison SC (1998) Structure of an IkappaBalpha/NF-kappaB complex. Cell 95:749–758. doi:10.1186/1743-422X-8-422

    Article  PubMed  CAS  Google Scholar 

  27. Funami K, Sasai M, Oshiumi H, Seya T, Matsumoto M (2008) Homo-oligomerization is essential for Toll/interleukin-1 receptor domain-containing adaptor molecule-1-mediated NF-kappaB and interferon regulatory factor-3 activation. J Biol Chem 283:18283–18291. doi:10.1074/jbc.M801013200

    Article  PubMed  CAS  Google Scholar 

  28. Oshiumi H, Matsumoto M, Funami K, Akazawa T, Seya T (2003) TICAM-1, an adaptor molecule that participates in Toll-like receptor 3-mediated interferon-beta induction. Nat Immunol 4:161–167. doi:10.1038/ni886

    Article  PubMed  CAS  Google Scholar 

  29. Peters RT, Liao SM, Maniatis T (2000) IKKepsilon is part of a novel PMA-inducible IkappaB kinase complex. Mol Cell 5:513–522. doi:10.1016/S1097-2765(00)80445-1

    Article  PubMed  CAS  Google Scholar 

  30. Chaudhary PM, Eby M, Jasmin A, Bookwalter A, Murray J, Hood L (1997) Death receptor 5, a new member of the TNFR family, and DR4 induce FADD-dependent apoptosis and activate the NF-kappaB pathway. Immunity 7:821–830. doi:10.1016/S1074-7613(00)80400-8

    Article  PubMed  CAS  Google Scholar 

  31. Dijkstra G, Moshage H, Jansen PL (2002) Blockade of NF-kappaB activation and donation of nitric oxide: new treatment options in inflammatory bowel disease? Scand J Gastroenterol 236(Suppl):37–41

    Article  Google Scholar 

  32. Luscinskas FW, Cybulsky MI, Kiely JM, Peckins CS, Davis VM, Gimbrone MA Jr (1991) Cytokine-activated human endothelial monolayers support enhanced neutrophil transmigration via a mechanism involving both endothelial-leukocyte adhesion molecule-1 and intercellular adhesion molecule-1. J Immunol 146:1617–1625

    PubMed  CAS  Google Scholar 

  33. Dippold W, Wittig B, Schwaeble W, Mayet W, Meyer zum Buschenfelde KH (1993) Expression of intercellular adhesion molecule 1 (ICAM-1, CD54) in colonic epithelial cells. Gut 34:1593–1597

    Article  PubMed  CAS  Google Scholar 

  34. Jobin C, Hellerbrand C, Licato LL, Brenner DA, Sartor RB (1998) Mediation by NF-kappa B of cytokine induced expression of intercellular adhesion molecule 1 (ICAM-1) in an intestinal epithelial cell line, a process blocked by proteasome inhibitors. Gut 42:779–787

    Article  PubMed  CAS  Google Scholar 

  35. Alderton WK, Cooper CE, Knowles RG (2001) Nitric oxide synthases: structure, function and inhibition. Biochem J 357:593–615

    Article  PubMed  CAS  Google Scholar 

  36. Shi W, Meininger CJ, Haynes TE, Hatakeyama K, Wu G (2004) Regulation of tetrahydrobiopterin synthesis and bioavailability in endothelial cells. Cell Biochem Biophys 41:415–434. doi:10.1385/CBB:41:3:415

    Article  PubMed  CAS  Google Scholar 

  37. Cui XL, Zhang JH, Ma PL, Myers DE, Goldberg IG, Sittler KJ, Barb JJ, Munson PJ, Cintron AD, McCoy JP, Wang SB, Danner RL (2005) cGMP-independent nitric oxide signaling and regulation of the cell cycle. BMC Genomics 6:151–168. doi:10.1186/1471-2164-6-151

    Article  PubMed  Google Scholar 

  38. Allaoui A, Botteaux A, Dumont JE, Hoste C, De Deken X (2009) Dual oxidases and hydrogen peroxide in a complex dialogue between host mucosae and bacteria. Trends Mol Med 15:571–579. doi:10.1016/J.Molmed.2009.10.003

    Article  PubMed  CAS  Google Scholar 

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Acknowledgment

This work was supported by a NSERC-discovery grant to DDK. We also thank Michael Friedmann (UBC plant science) for assistance with real-time PCR.

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  1. Food, Nutrition, and Health, Faculty of Land and Food Systems, University of British Columbia, 2205 East Mall, Vancouver, BC, V6T 1Z4, Canada

    Xiu-Min Chen & David D. Kitts

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Correspondence to David D. Kitts.

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Chen, XM., Kitts, D.D. Characterization of antioxidant and anti-inflammatory activities of bioactive fractions recovered from a glucose−lysine Maillard reaction model system. Mol Cell Biochem 364, 147–157 (2012). https://doi.org/10.1007/s11010-011-1213-7

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