Skip to main content

Advertisement

Log in

Cinnamaldehyde is the main mediator of cinnamon extract in mast cell inhibition

  • Original Contribution
  • Published:
European Journal of Nutrition Aims and scope Submit manuscript

Abstract

Purpose

In terms of their involvement in allergic and inflammatory conditions, mast cells (MC) can be promising targets for medical agents in therapy. Because of their good compliance and effectiveness, phytochemicals are of great interest as new therapeutic tools in form of nutraceuticals. We found recently that cinnamon extract (CE) inhibits mast cell activation. Here, we analysed the effects of a major compound of CE, cinnamaldehyde (CA), on mast cell activation.

Methods

Release of prestored and de novo synthesised mediators as well as expression of pro-inflammatory cytokines and mast cell-specific proteases were analysed in RBL-2H3 cells or in human mast cells isolated from intestinal tissue (hiMC) treated with CA prior to stimulation by FcεRI crosslinking or IONO/PMA. The results were compared with the corresponding effects of CE.

Results

Following treatment with CA, release of β-hexosaminidase in IgE-dependent or IgE-independent activated RBL-2H3 cells was down-regulated in a dose-dependent manner to about 10 %. In hiMC, release of β-hexosaminidase was also significantly reduced, and release of LTC4 and CXCL8 was almost completely inhibited by CA. Moreover, IgE-mediated expression of CXCL8, CCL2, CCL3 and CCL4 in hiMC was significantly down-regulated by CA. With the exception of the expression of the mast cell proteases tryptase and chymase, the inhibitory effects of CA were very similar to the effects shown for CE treatment. The reducing effect of CA on mast cell mediators—seen for long- and for short-term incubations—could be related to particular signalling pathways as CA caused a down-regulation in ERK as well as PLCγ1 phosphorylation.

Conclusions

CA decreases release and expression of pro-inflammatory mast cell mediators. This inhibitory action is similar to the effects observed for CE indicating CA as the main active compound in CE leading to its anti-allergic properties.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

References

  1. Kiyohara C, Tanaka K (2008) Genetic susceptibility to atopic dermatitis. Allergol Int 57:39–56

    Article  CAS  Google Scholar 

  2. Gupta R, Sheikh A, Strachan DP, Anderson HR (2007) Time trends in allergic disorders in the UK. Thorax 62:91–96

    Article  CAS  Google Scholar 

  3. Molodecky NA, Soon IS, Rabi DM, Ghali WA, Ferris M, Chernoff G, Benchimol EI, Panaccione R, Ghosh S, Barkema HW, Kaplan GG (2012) Increasing incidence and prevalence of the inflammatory bowel diseases with time, based on systematic review. Gastroenterology 142:46–54 e42

    Article  Google Scholar 

  4. Chai OH, Han E-H, Lee H-K, Song CH (2011) Mast cells play a key role in Th2 cytokine dependent asthma model through production of adhesion molecules by liberation of TNF-α. Exp Mol Med 43:35–43

    Article  CAS  Google Scholar 

  5. Jacob C, Yang P-C, Darmoul D, Amadesi S, Saito T, Cottrell GS, Coelho A-M, Singh P, Grady EF, Perdue M, Bunnett NW (2005) Mast cell tryptase controls paracellular permeability of the intestine: role of protease-activated receptor 2 and β-arrestins. J Biol Chem 280:31936–31948

    Article  CAS  Google Scholar 

  6. Hamilton MJ, Sinnamon MJ, Lyng GD, Glickman JN, Wang X, Xing W, Krilis SA, Blumberg RS, Adachi R, Lee DM, Stevens RL (2011) Essential role for mast cell tryptase in acute experimental colitis. PNAS 108:290–295

    Article  CAS  Google Scholar 

  7. Larmonier CB, Midura-Kiela MT, Ramalingam R, Laubitz D, Janikashvili N, Larmonier N, Ghishan FK, Kiela PR (2011) Modulation of neutrophil motility by curcumin: implications for inflammatory bowel disease. Inflamm Bowel Dis 17:503–515

    Article  CAS  Google Scholar 

  8. Sergent T, Piront N, Meurice J, Toussaint O, Schneider Y-J (2010) Anti-inflammatory effects of dietary phenolic compounds in an in vitro model of inflamed human intestinal epithelium. Chem Biol Interact 188:659–667

    Article  CAS  Google Scholar 

  9. Hagenlocher Y, Lorentz A (2015) Immunomodulation of mast cells by nutrients. Mol Immunol 63:25–31

  10. Itoh T, Hori Y, Atsumi T, Toriizuka K, Nakamura M, Maeyama T, Ando M, Tsukamasa Y, Ida Y, Furuichi Y (2012) Hot water extract of adzuki (Vigna angularis) suppresses antigen-stimulated degranulation in rat basophilic leukemia RBL-2H3 cells and passive cutaneous anaphylaxis reaction in mice. Phytother Res 26:1003–1011

    Article  Google Scholar 

  11. Lee JH, Kim JW, Ko NY, Mun SH, Her E, Kim BK, Han JW, Lee HY, Beaven MA, Kim YM, Choi WS (2008) Curcumin, a constituent of curry, suppresses IgE-mediated allergic response and mast cell activation at the level of Syk. J Allergy Clin Immunol 121:1225–1231

    Article  CAS  Google Scholar 

  12. Li GZ, Chai OH, Song CH (2005) Inhibitory effects of epigallocatechin gallate on compound 48/80-induced mast cell activation and passive cutaneous anaphylaxis. Exp Mol Med 37:290–296

    Article  CAS  Google Scholar 

  13. Bischoff SC (2007) Role of mast cells in allergic and non-allergic immune responses: comparison of human and murine data. Nat Rev Immunol 7:93–104

    Article  CAS  Google Scholar 

  14. Bischoff SC (2009) Physiological and pathophysiological functions of intestinal mast cells. Semin Immunopathol 31:185–205

    Article  CAS  Google Scholar 

  15. Kalesnikoff J, Galli SJ (2008) New developments in mast cell biology. Nat Immunol 9(11):1215–1223

    Article  CAS  Google Scholar 

  16. Galli SJ, Grimbaldeston M, Tsai M (2008) Immunomodulatory mast cells: negative, as well as positive, regulators of innate and acquired immunity. Nat Rev Immunol 8(6):478–486

    Article  CAS  Google Scholar 

  17. Kopeć A, Panaszek B, Fal AM (2006) Intracellular signaling pathways in IgE-dependent mast cell activation. Arch Immunol Ther Exp 54:393–401

    Article  Google Scholar 

  18. Roussel AM, Hininger I, Benaraba R, Ziegenfuss TN, Anderson RA (2009) Antioxidant effects of a cinnamon extract in people with impaired fasting glucose that are overweight or obese. JACN 28(1):16–21

    Article  CAS  Google Scholar 

  19. Kannappan S, Jayaraman T, Rajasekar P, Ravichandran MK, Anuradha CV (2006) Cinnamon bark extract improves glucose metabolism and lipid profile in the fructose-fed rat. Singap Med J 47(10):858–863

    CAS  Google Scholar 

  20. Nahas R, Moher M (2009) Complementary and alternative medicine for the treatment of type 2 diabetes. Can Fam Physician 55:591–596

    Google Scholar 

  21. Kwon HK, Hwang JS, So JS et al (2010) Cinnamon extract induces tumor cell death through inhibition of NFkappaB and AP1. BMC Cancer 10:392–401

    Article  Google Scholar 

  22. Bai SK, Lee SJ, Na HJ et al (2005) Beta-carotene inhibits inflammatory gene expression in lipopolysaccharide-stimulated macrophages by suppressing redox-based NF-kappaB activation. Exp Mol Med 37(4):323–334

    Article  CAS  Google Scholar 

  23. Koppikar SJ, Choudhari AS, Suryavanshi SA, Kumari S, Chattopadhyay S, Kaul-Ghanekar R (2010) Aqueous cinnamon extract (ACE-c) from the bark of Cinnamomum cassia causes apoptosis in human cervical cancer cell line (SiHa) through loss of mitochondrial membrane potential. BMC Cancer 10:210–221

    Article  Google Scholar 

  24. Hagenlocher Y, Bergheim I, Zacheja S, Schäffer M, Bischoff SC, Lorentz A (2013) Cinnamon extract inhibits degranulation and de novo synthesis of inflammatory mediators in mast cells. Allergy 68(4):490–497

    Article  CAS  Google Scholar 

  25. Corren J, Lemay M, Lin YRL, Randolph RK (2008) Clinical and biochemical effects of a combination botanical product (ClearGuard™) for allergy: a pilot randomized double-blind placebo-controlled trial. J Nutr 7:20–28

    Article  Google Scholar 

  26. Gruenwald J, Freder J, Armbruester N (2010) Cinnamon and health. Crit Rev Food Sci Nutr 50(9):822–834

    Article  Google Scholar 

  27. Chericoni S, Prieto JM, Iacopini P, Cioni P, Morelli I (2005) In vitro activity of the essential oil of Cinnamomum zeylanicum and eugenol in peroxynitrite-induced oxidative processes. J Agric Food Chem 53(12):4762–4765

    Article  CAS  Google Scholar 

  28. Zhang J-H, Liu L-Q, He Y-L, Kong W-J, Huang S-A (2010) Cytotoxic effect of transcinnamaldehyde on human leukemia K562 cells. Acta Pharmacol Sin 31:861–866

    Article  Google Scholar 

  29. Cabello CM, Bair WB III, Lamore SD, Ley S, Bause AS, Azimian S, Wondrak GT (2009) The cinnamon-derived Michael acceptor cinnamic aldehyde impairs melanoma cell proliferation, invasiveness, and tumor growth. Free Radic Biol Med 46:220–231

    Article  CAS  Google Scholar 

  30. Hayashi K, Imanishi N, Kashiwayama Y, Kawano A, Terasawa K, Shimada Y, Ochiai H (2007) Inhibitory effect of cinnamaldehyde, derived from Cinnamomi cortex, on the growth of influenza A/PR/8 virus in vitro and in vivo. Antiviral Res 74:1–8

    Article  CAS  Google Scholar 

  31. Upadhyay A, Upadhyaya I, Kollanoor-Johny A, Venkitanarayanan K (2013) Antibiofilm effect of plant derived antimicrobials on Listeria monocytogenes. Food Microbiol 36:79–89

    Article  CAS  Google Scholar 

  32. Kollanoor-Johny A, Mattson T, Baskaran SA, Amalaradjou MA, Babapoor S, March B, Valipe S, Darre M, Hoagland T, Schreiber D et al (2012) Reduction of Salmonella enterica serovar enteritidis colonization in 20-day-old broiler chickens by the plant-derived compounds trans-cinnamaldehyde and eugenol. Appl Environ Microbiol 78:2981–2987

    Article  CAS  Google Scholar 

  33. Ali SM, Khan AA, Ahmed I, Musaddiq M, Ahmed KS, Polasa H, Rao LV, Habibullah CM, Sechi LA, Ahmed N (2005) Antimicrobial activities of Eugenol and Cinnamaldehyde against the human gastric pathogen Helicobacter pylori. Ann Clin Microbiol Antimicrob 4:1–7

    Article  Google Scholar 

  34. Alpizar YA, Gees M, Sanchez A, Apetrei A, Voets T, Nilius B, Talavera K (2013) Bimodal effects of cinnamaldehyde and camphor on mouse TRPA1. Pflugers Arch-Eur J Physiol 465:853–864

    Article  CAS  Google Scholar 

  35. Huang B, Yuan HD, Kim DY, Quan HY, Chung SH (2011) Cinnamaldehyde prevents adipocyte differentiation and adipogenesis via regulation of peroxisome proliferator-activated receptor-γ (PPARγ) and AMP-activated protein kinase (AMPK) pathways. J Agric Food Chem 59:3666–3673

    Article  CAS  Google Scholar 

  36. Anand P, Murali KY, Tandon V, Murthy PS, Chandra R (2010) Insulinotropic effect of cinnamaldehyde on transcriptional regulation of pyruvate kinase, phosphoenolpyruvate carboxykinase, and GLUT4 translocation in experimental diabetic rats. Chem Biol Interact 186:72–81

    Article  CAS  Google Scholar 

  37. Chao LK, Hua KF, Hsu HY, Cheng SS, Lin IF, Chen CJ, Chen ST, Chang ST (2008) Cinnamaldehyde inhibits pro-inflammatory cytokines secretion from monocytes/macrophages through suppression of intracellular signaling. Food Chem Toxicol 46:220–231

    Article  CAS  Google Scholar 

  38. Lorentz A, Sellge G, Bischoff SC (2015) Isolation, culture, and characterization of intestinal mast cells. Methods Mol Biol 1220:163–177

    Article  Google Scholar 

  39. Feuser K, Feilhauer K, Staib L, Bischoff SC, Lorentz A (2011) Akt cross-links IL-4 priming, stem cell factor signaling, and IgE-dependent activation in mature human mast cells. Mol Immunol 48:546–552

    Article  CAS  Google Scholar 

  40. Schwartz LB, Austen KF, Wasserman SI (1979) Immunological release of betahexosaminidase and beta-glucoronidase from purified rat serosal mast cells. J Immunol 123:1445–1450

    CAS  Google Scholar 

  41. Lorentz A, Wilke M, Sellge G, Worthmann H, Klempnauer J, Manns MP et al (2005) IL-4 induced priming of human intestinal mast cells for enhanced survival and Th2 cytokine generation is reversible and associated with increased activity of ERK1/2 and c-FOS. J Immunol 174:6751–6756

    Article  CAS  Google Scholar 

  42. Ehlers D, Hilmer S, Bartholomae S (1995) HPLC analysis of supercritical CO2 cinnamon and cassia extracts in comparison with cinnamon and cassia oils. Z Lebensm Unters Forsch 200:282–288

    Article  CAS  Google Scholar 

  43. Kageyama-Yahara N, Wang X, Katagiri T, Wang P, Yamamoto T, Tominaga M, Kadowaki M (2011) Suppression of phospholipase Cγ1 phosphorylation by cinnamaldehyde inhibits antigen-induced extracellular calcium influx and degranulation in mucosal mast cells. Biochem Biophys Res Commun 416:283–288

    Article  CAS  Google Scholar 

  44. Lorentz A, Klopp I, Gebhardt T, Manns MP, Bischoff SC (2003) Role of activator protein 1, nuclear factor-κB, and nuclear factor of activated T cells in IgE receptormediated cytokine expression in mature human mast cells. J Allergy Clin Immunol 111:1062–1068

    Article  CAS  Google Scholar 

  45. Kimata M, Inagaki N, Kato T, Miura T, Serizawa I, Nagai H (2000) Roles of mitogenactivated protein kinase pathways for mediator release from human cultured mast cells. Biochem Pharmacol 60:589–594

    Article  CAS  Google Scholar 

  46. Kuehn HS, Swindle EJ, Kim M-S, Beaven MA, Metcalfe DD, Gilfillan AM (2008) The phosphoinositide 3-kinase-dependent activation of Btk is required for optimal eicosanoid production and generation of reactive oxygen species in antigenstimulated mast cells. J Immunol 181:7706–7712

    Article  CAS  Google Scholar 

  47. Lee Y-N, Tuckerman J, Nechushtan H, Schutz G, Razin E, Angel P (2004) c-Fos as a regulator of degranulation and cytokine production in FcεRI-activated mast cells. J Immunol 173:2571–2577

    Article  CAS  Google Scholar 

  48. Chang F, Steelman LS, Lee JT, Shelton JG, Navolanic PM, Blalock WL, Franklin RA, McCubrey JA (2003) Signal transduction mediated by the Ras/Raf/MEK/ERK pathway from cytokine receptors to transcription factors: potential targeting for therapeutic intervention. Leukemia 17:1263–1293

    Article  CAS  Google Scholar 

  49. Banks C, Bateman A, Payne R, Johnson P, Sheron N (2003) Chemokine expression in IBD. Mucosal chemokine expression is unselectively increased in both ulcerative colitis and Crohn’s disease. J Pathol 199:28–35

    Article  Google Scholar 

  50. Matsuda R, Koide T, Tokoro C, Yamamoto T, Godai T, Morohashi T, Fujita Y, Takahashi D, Kawana I, Suzuki S, Umemura S (2009) Quantitive cytokine mRNA expression profiles in the colonic mucosa of patients with steroid naïve ulcerative colitis during active and quiescent disease. Inflamm Bowel Dis 15:328–334

    Article  Google Scholar 

  51. Uguccioni M, Gionchetti P, Robbiani DF, Rizzello F, Peruzzo S, Campieri M, Baggiolini M (1999) Increased expression of IP-10, IL-8, MCP-1, and MCP-3 in ulcerative colitis. Am J Pathol 155:331–336

    Article  CAS  Google Scholar 

  52. Irani AM, Bradford TR, Kepley CL, Schechter NM, Schwartz LB (1989) Detection of MCT and MCTC types of human mast cells by immunohistochemistry using new monoclonal anti-tryptase and anti-chymase antibodies. J Histochem Cytochem 37:1509–1515

    Article  CAS  Google Scholar 

  53. Wastling JM, Scudamore CL, Thornton EM, Newlands GFJ, Miller HRP (1997) Constitutive expression of mouse mast cell protease-1 in normal BALB/c mice and its upregulation during intestinal nematode infection. Immunology 90:308–313

    Article  CAS  Google Scholar 

  54. Kim HM, Lee EH, Kim CY, Chung JG, Kim SH, Lim JP, Shin TY (1997) Antianaphylactic properties of eugenol. Pharmacol Res 36(6):475–480

    Article  CAS  Google Scholar 

  55. Lee JH, Kim JW, Ko NY, Mun SH, Kim DK, Kim JD, Kim HS, Lee KR, Kim YK, Radinger M, Her E, Choi WS (2008) Camellia japonica suppresses immunoglobulin E-mediated allergic response by the inhibition of Syk kinase activation in mast cells. Clin Exp Allergy 38:794–804

    Article  CAS  Google Scholar 

Download references

Acknowledgments

The authors thank Yvonne Soltow for excellent technical assistance.

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical standard

Surgery tissue specimen from patients undergoing bowel resection served for isolation of mature human MC. This study has been approved by the local ethics committee and has therefore been performed in accordance with the ethical standards. All persons gave their informed consent prior to their inclusion in the study.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Axel Lorentz.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Hagenlocher, Y., Kießling, K., Schäffer, M. et al. Cinnamaldehyde is the main mediator of cinnamon extract in mast cell inhibition. Eur J Nutr 54, 1297–1309 (2015). https://doi.org/10.1007/s00394-014-0810-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00394-014-0810-0

Keywords

Navigation