Phytomedicine
Volume 16, Issue 5 , Pages 477-484 , May 2009

Herbal melanin activates TLR4/NF-κB signaling pathway

  • Fredrik Öberg

      Affiliations

    • Department of Genetics and Pathology, Rudbeck Laboratory, Uppsala University Hospital, SE-751 85 Uppsala, Sweden
  • ,
  • Adil Haseeb

      Affiliations

    • Faculty of Science, King Saud University, Riyadh, Saudi Arabia
  • ,
  • Matilda Ahnfelt

      Affiliations

    • Department of Genetics and Pathology, Rudbeck Laboratory, Uppsala University Hospital, SE-751 85 Uppsala, Sweden
  • ,
  • Fredrik Pontén

      Affiliations

    • Department of Genetics and Pathology, Rudbeck Laboratory, Uppsala University Hospital, SE-751 85 Uppsala, Sweden
  • ,
  • Bengt Westermark

      Affiliations

    • Department of Genetics and Pathology, Rudbeck Laboratory, Uppsala University Hospital, SE-751 85 Uppsala, Sweden
  • ,
  • Adila El-Obeid

      Affiliations

    • Department of Genetics and Pathology, Rudbeck Laboratory, Uppsala University Hospital, SE-751 85 Uppsala, Sweden
    • Corresponding Author InformationCorresponding author. Tel.: +46186113838; fax: +4618552739.

References 

  1. Ashkenazi A, Dixit VM. Death receptors: signaling and modulation. Science. 1998;281:1305–1308
  2. Avramidis N, Kourounakis A, Hadjipetrou L, Senchuk V. Anti-inflammatory and immunomodulating properties of grape melanin. Inhibitory effects on paw edema and adjuvant induced disease. Arzneimittelforschung. 1998;48:764–771
  3. Bannerman DD, Erwert RD, Winn RK, Harlan JM. TIRAP mediates endotoxin-induced NF-kappaB activation and apoptosis in endothelial cells. Biochem. Biophys. Res. Commun. 2002;295:157–162
  4. Binding N, Jaschinski S, Werlich S, Bletz S, Witting U. Quantification of bacterial lipopolysaccharides (endotoxin) by GC–MS determination of 3-hydroxy fatty acids. J. Environ. Monit. 2004;6:65–70
  5. Brandenburg K, Jürgens G, Müller M, Fukuoka S, Koch MH. Biophysical characterization of lipopolysaccharide and lipid A inactivation by lactoferrin. Biol. Chem. 2001;382:1215–1225
  6. Brandenburg K, Matsuura M, Heine H, Müller M, Kiso M, Ishida H, et al. Biophysical characterization of triacyl monosaccharide lipid a partial structures in relation to bioactivity. Biophys. J. 2002;83:322–333
  7. Burke JR, Pattoli MA, Gregor KR, Brassil PJ, MacMaster JF, McIntyre KW, et al. BMS-345541 is a highly selective inhibitor of I kappa B kinase that binds at an allosteric site of the enzyme and blocks NF-kappa B-dependent transcription in mice. J. Biol. Chem. 2003;278:1450–1456
  8. Cižnár I, Shands JW. Effect of alkali on the immunological reactivity of lipopolysaccharide from Salmonella typhimurium. Infect. Immun. 1970;2:549–555
  9. Covert MW, Leung TW, Gaston JE, Baltimore D. Achieving stability of lipopolysaccharide-induced NF-kappaB activation. Science. 2005;309:1854–1857
  10. El-Obeid A, Al-Harbi S, Al-Jomah N, Hassib A. Herbal melanin modulates tumor necrosis factor alpha (TNF-alpha), interleukin 6 (IL-6) and vascular endothelial growth factor (VEGF) production. Phytomedicine. 2006;13:324–333
  11. El-Obeid A, Hassib A, Pontén F, Westermark B. Effect of herbal melanin on IL-8: a possible role of Toll-like receptor 4 (TLR4). Biochem. Biophys. Res. Commun. 2006;344:1200–1206
  12. Festjens N, Vanden Berghe T, Cornelis S, Vandenabeele P. RIP1, a kinase on the crossroads of a cell's decision to live or die. Cell Death Differ. 2007;14:400–410
  13. Frey EA, Miller DS, Jahr TG, Sundan A, Bazil V, Espevik T, et al. Soluble CD14 participates in the response of cells to lipopolysaccharide. J. Exp. Med. 1992;176:1665–1671
  14. Haase R, Kirschning CJ, Sing A, Schrottner P, Fukase K, Kusumoto S, et al. A dominant role of Toll-like receptor 4 in the signaling of apoptosis in bacteria-faced macrophages. J. Immunol. 2003;171:4294–4303
  15. Haskins WT, Landy M, Milner KC, Ribi E. Biological properties of parent endotoxins and lipoid fractions, with a kinetic study of acid-hydrolyzed endotoxin. J. Exp. Med. 1961;114:665–684
  16. Hassib, A., 1998. Extraction of melanin from Nigella sativa L., Patent No. 451, Khartoum, Sudan.
  17. Hayden MS, Ghosh S. Signaling to NF-kappaB. Genes Dev. 2004;18:2195–2224
  18. Hoshino K, Takeuchi O, Kawai T, Sanjo H, Ogawa T, Takeda Y, et al. Toll-like receptor 4 (TLR4)-deficient mice are hyporesponsive to lipopolysaccharide: evidence for TLR4 as the Lps gene product. J. Immunol. 1999;162:3749–3752
  19. Jürgens G, Müller M, Koch MH, Brandenburg K. Interaction of hemoglobin with enterobacterial lipopolysaccharide and lipid A. Physicochemical characterization and biological activity. Eur. J. Biochem. 2001;268:4233–4242
  20. Kopp E, Medzhitov R. Recognition of microbial infection by Toll-like receptors. Curr. Opin. Immunol. 2003;15:396–401
  21. Lemmers B, Salmena L, Bidère N, Su H, Matysiak-Zablocki E, Murakami K, et al. Essential role for caspase-8 in Toll-like receptors and NFkappaB signaling. J. Biol. Chem. 2007;282:7416–7423
  22. Luo JL, Kamata H, Karin M. IKK/NF-kappaB signaling: balancing life and death--a new approach to cancer therapy. J. Clin. Invest. 2005;115:2625–2632
  23. Medzhitov R, Preston-Hurlburt P, Janeway Jr CA. A human homologue of the Drosophila Toll protein signals activation of adaptive immunity. Nature. 1997;388:394–397
  24. Meylan E, Tschopp J. The RIP kinases: crucial integrators of cellular stress. Trends Biochem. Sci. 2005;30:151–159(Review)
  25. Müller-Loennies S, Zähringer U, Seydel U, Kusumoto S, Ulmer AJ, Rietschel ET. What we know and don’t know about the chemical and physical structure of lipopolysaccharide in relation to biological activity. Prog. Clin. Biol. Res. 1998;397:51–72
  26. Nakayama GR, Caton MC, Nova MP, Parandoosh Z. Assessment of the Alamar Blue assay for cellular growth and viability in vitro. J. Immunol. Methods. 1997;204:205–208
  27. Nosanchuk JD, Rosas AL, Casadevall A. The antibody response to fungal melanin in mice. J. Immunol. 1998;160:6026–6031
  28. O’Neill AL, Bowie AG. The family of five: TIR-domain-containing adaptors in Toll-like receptor signalling. Nat. Rev. Immunol. 2007;7:353–364
  29. Poltorak A, He X, Smirnova I, Liu MY, Van Huffel C, Du X, et al. Defective LPS signaling in C3H/HeJ and C57BL/10ScCr mice: mutations in Tlr4 gene. Science. 1998;282:2085–2088
  30. Pugh ND, Balachandran P, Lata H, Dayan FE, Joshi V, Bedir E, et al. Melanin: dietary mucosal immune modulator from Echinacea and other botanical supplements. Int. Immunopharmacol. 2005;5:637–647
  31. Pugh ND, Tamta H, Balachandran P, Wu X, Howell J, Dayan FE, et al. The majority of in vitro macrophage activation exhibited by extracts of some immune enhancing botanicals is due to bacterial lipoproteins and lipopolysaccharides. Int. Immunopharmacol. 2008;8:1023–1032
  32. Riedl SJ, Salvesen GS. The apoptosome: signalling platform of cell death. Nat. Rev. Mol. Cell Biol. 2007;8:405–413
  33. Riley PA. Molecules in focus: melanin. Int. J. Biochem. Cell Biol. 1997;29:1235–1239
  34. Ruckdeschel K, Pfaffinger G, Haase R, Sing A, Weighardt H, Hacker G, et al. Signaling of apoptosis through TLRs critically involves toll/IL-1 receptor domain-containing adapter inducing IFN-β, but not MyD88, in bacteria-infected murine macrophages. J. Immunol. 2004;173:3320–3328
  35. Sava V, Galkin B, Hong MY, Yang PC, Huang GS. A novel melanin-like pigment derived from black tea leaves with immuno-stimulating activity. Food Res. Int. 2001;34:337–343
  36. Shimazu R, Akashi S, Ogata H, Nagai Y, Fukudome K, Miyake K, et al. MD-2, a molecule that confers lipopolysaccharide responsiveness on Toll-like receptor 4. J. Exp. Med. 1999;189:1777–1782
  37. Silipo A, Lanzetta R, Amoresano A, Parrilli M, Molinaro A. Ammonium hydroxide hydrolysis: a valuable support in the MALDI-TOF mass spectrometry analysis of lipid A fatty acid distribution. J. Lipid Res. 2002;43:2188–2195
  38. Somlyo B, Csanky E, Shi XM, Zhang YL, Kovats E, Bona-Liptak E, et al. Molecular requirements of endotoxin (ET) actions: changes in the immune adjuvant, TNF liberating and toxic properties of endotoxin during alkaline hydrolysis. Int. J. Immunopharmacol. 1992;14:131–142
  39. Takeda K, Akira S. Toll-like receptors in innate immunity. Int. Immunol. 2005;17:1–14
  40. Tanamoto K. Dissociation of endotoxic activities in a chemically synthesized lipid A precursor after acetylation. Infect. Immun. 1995;63:690–692
  41. Waelchli R, Bollbuck B, Bruns C, Buhl T, Eder J, Feifel R, et al. Design and preparation of 2-benzamido-pyrimidines as inhibitors of IKK. Bioorg. Med. Chem. Lett. 2006;16:108–112
  42. Wang CY, Mayo MW, Baldwin AS. TNF- and cancer therapy-induced apoptosis: potentiation by inhibition of NF-kappaB. Science. 1996;274:784–787
  43. Wilms H, Rosenstiel P, Sievers J, Deuschl G, Zecca L, Lucius R. Activation of microglia by human neuromelanin is NF-kappaB dependent and involves p38 mitogen-activated protein kinase: implications for Parkinson's disease. FASEB J. 2003;17:500–502
  44. Xue X, Lai KT, Huang JF, Gu Y, Karlsson L, Fourie A. Anti-inflammatory activity in vitro and in vivo of the protein farnesyltransferase inhibitor tipifarnib. J. Pharmacol. Exp. Ther. 2006;317:53–60
  45. Yamamoto M, Sato S, Hemmi H, Hoshino K, Kaisho T, Sanjo H, et al. Role of adaptor TRIF in the MyD88-independent Toll-like receptor signaling pathway. Science. 2003;301:640–643
  46. Yang S, Tamai R, Akashi S, Takeuchi O, Akira S, Sugawara S, et al. Synergistic effect of muramyldipeptide with lipopolysaccharide or lipoteichoic acid to induce inflammatory cytokines in human monocytic cells in culture. Infect. Immun. 2001;69:2045–2053
  47. Zeise L. Analytical methods for characterization and identification of eumelanins. In:  Zeise L,  Chedekel MR,  Fitzpatrick TB editor. Melanin: Its Role in Human Photoprotection. Overland Park, Kansas: Valdenmar Publishing; 1995;p. 65–79
  48. Zhi-Jun Y, Sriranganathan N, Vaught T, Arastu SK, Ahmed SA. A dye-based lymphocyte proliferation assay that permits multiple immunological analyses: mRNA, cytogenetic, apoptosis, and immunophenotyping studies. J. Immunol. Methods. 1997;210:25–39
  49. Zhong J, Frases S, Wang H, Casadevall A, Stark RE. Following fungal melanin biosynthesis with solid-state NMR: biopolymer molecular structures and possible connections to cell-wall polysaccharides. Biochemistry. 2008;47:4701–4710

PII: S0944-7113(08)00195-5

doi: 10.1016/j.phymed.2008.10.008

Phytomedicine
Volume 16, Issue 5 , Pages 477-484 , May 2009