The cannabinoid TRPA1 agonist cannabichromene inhibits nitric oxide production in macrophages and ameliorates murine colitis

B. Romano, F. Borrelli, I. Fasolino, R. Capasso, F. Piscitelli, M.G. Cascio, R.G. Pertwee, D. Coppola, L. Vassallo, P. Orlando, V. Di Marzo, A.A. Izzo

Research output: Contribution to journalArticle

62 Citations (Scopus)

Abstract

Background and Purpose
The non-psychotropic cannabinoid cannabichromene is known to activate the transient receptor potential ankyrin-type1 (TRPA1) and to inhibit endocannabinoid inactivation, both of which are involved in inflammatory processes. We examined here the effects of this phytocannabinoid on peritoneal macrophages and its efficacy in an experimental model of colitis.

Experimental Approach
Murine peritoneal macrophages were activated in vitro by LPS. Nitrite levels were measured using a fluorescent assay; inducible nitric oxide (iNOS), cyclooxygenase-2 (COX-2) and cannabinoid (CB1 and CB2) receptors were analysed by RT-PCR (and/or Western blot analysis); colitis was induced by dinitrobenzene sulphonic acid (DNBS). Endocannabinoid (anandamide and 2-arachidonoylglycerol), palmitoylethanolamide and oleoylethanolamide levels were measured by liquid chromatography-mass spectrometry. Colonic inflammation was assessed by evaluating the myeloperoxidase activity as well as by histology and immunohistochemistry.

Key Results
LPS caused a significant production of nitrites, associated to up-regulation of anandamide, iNOS, COX-2, CB1 receptors and down-regulation of CB2 receptors mRNA expression. Cannabichromene significantly reduced LPS-stimulated nitrite levels, and its effect was mimicked by cannabinoid receptor and TRPA1 agonists (carvacrol and cinnamaldehyde) and enhanced by CB1 receptor antagonists. LPS-induced anandamide, iNOS, COX-2 and cannabinoid receptor changes were not significantly modified by cannabichromene, which, however, increased oleoylethanolamide levels. In vivo, cannabichromene ameliorated DNBS-induced colonic inflammation, as revealed by histology, immunohistochemistry and myeloperoxidase activity.

Conclusion and Implications
Cannabichromene exerts anti-inflammatory actions in activated macrophages – with tonic CB1 cannabinoid signalling being negatively coupled to this effect – and ameliorates experimental murine colitis.
Original languageEnglish
Pages (from-to)213-229
Number of pages16
JournalBritish Journal of Pharmacology
Volume169
Issue number1
Early online date12 Apr 2013
DOIs
Publication statusPublished - May 2013

Fingerprint

Ankyrins
Cannabinoid Receptors
Colitis
Cannabinoid Receptor CB1
Nitric Oxide
Cyclooxygenase 2
Nitrites
Macrophages
Dinitrobenzenes
Cannabinoid Receptor CB2
Endocannabinoids
Sulfonic Acids
Cannabinoids
Peritoneal Macrophages
Peroxidase
Histology
Immunohistochemistry
Inflammation
Liquid Chromatography
Mass Spectrometry

Keywords

  • cannabichromene
  • cannabinoid receptors
  • endocannabinoids
  • inflammatory bowel disease
  • macrophages
  • nitric oxide
  • non-psychotropic cannabinoids
  • oleoylethanolamide
  • transient receptor potential (TRP) channels
  • TRPA1

Cite this

Romano, B., Borrelli, F., Fasolino, I., Capasso, R., Piscitelli, F., Cascio, M. G., ... Izzo, A. A. (2013). The cannabinoid TRPA1 agonist cannabichromene inhibits nitric oxide production in macrophages and ameliorates murine colitis. British Journal of Pharmacology, 169(1), 213-229. https://doi.org/10.1111/bph.12120

The cannabinoid TRPA1 agonist cannabichromene inhibits nitric oxide production in macrophages and ameliorates murine colitis. / Romano, B. ; Borrelli, F. ; Fasolino, I. ; Capasso, R.; Piscitelli, F.; Cascio, M.G.; Pertwee, R.G.; Coppola, D. ; Vassallo, L. ; Orlando, P.; Di Marzo, V.; Izzo, A.A.

In: British Journal of Pharmacology, Vol. 169, No. 1, 05.2013, p. 213-229.

Research output: Contribution to journalArticle

Romano, B, Borrelli, F, Fasolino, I, Capasso, R, Piscitelli, F, Cascio, MG, Pertwee, RG, Coppola, D, Vassallo, L, Orlando, P, Di Marzo, V & Izzo, AA 2013, 'The cannabinoid TRPA1 agonist cannabichromene inhibits nitric oxide production in macrophages and ameliorates murine colitis', British Journal of Pharmacology, vol. 169, no. 1, pp. 213-229. https://doi.org/10.1111/bph.12120
Romano, B. ; Borrelli, F. ; Fasolino, I. ; Capasso, R. ; Piscitelli, F. ; Cascio, M.G. ; Pertwee, R.G. ; Coppola, D. ; Vassallo, L. ; Orlando, P. ; Di Marzo, V. ; Izzo, A.A. / The cannabinoid TRPA1 agonist cannabichromene inhibits nitric oxide production in macrophages and ameliorates murine colitis. In: British Journal of Pharmacology. 2013 ; Vol. 169, No. 1. pp. 213-229.
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T1 - The cannabinoid TRPA1 agonist cannabichromene inhibits nitric oxide production in macrophages and ameliorates murine colitis

AU - Romano, B.

AU - Borrelli, F.

AU - Fasolino, I.

AU - Capasso, R.

AU - Piscitelli, F.

AU - Cascio, M.G.

AU - Pertwee, R.G.

AU - Coppola, D.

AU - Vassallo, L.

AU - Orlando, P.

AU - Di Marzo, V.

AU - Izzo, A.A.

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AB - Background and PurposeThe non-psychotropic cannabinoid cannabichromene is known to activate the transient receptor potential ankyrin-type1 (TRPA1) and to inhibit endocannabinoid inactivation, both of which are involved in inflammatory processes. We examined here the effects of this phytocannabinoid on peritoneal macrophages and its efficacy in an experimental model of colitis.Experimental ApproachMurine peritoneal macrophages were activated in vitro by LPS. Nitrite levels were measured using a fluorescent assay; inducible nitric oxide (iNOS), cyclooxygenase-2 (COX-2) and cannabinoid (CB1 and CB2) receptors were analysed by RT-PCR (and/or Western blot analysis); colitis was induced by dinitrobenzene sulphonic acid (DNBS). Endocannabinoid (anandamide and 2-arachidonoylglycerol), palmitoylethanolamide and oleoylethanolamide levels were measured by liquid chromatography-mass spectrometry. Colonic inflammation was assessed by evaluating the myeloperoxidase activity as well as by histology and immunohistochemistry.Key ResultsLPS caused a significant production of nitrites, associated to up-regulation of anandamide, iNOS, COX-2, CB1 receptors and down-regulation of CB2 receptors mRNA expression. Cannabichromene significantly reduced LPS-stimulated nitrite levels, and its effect was mimicked by cannabinoid receptor and TRPA1 agonists (carvacrol and cinnamaldehyde) and enhanced by CB1 receptor antagonists. LPS-induced anandamide, iNOS, COX-2 and cannabinoid receptor changes were not significantly modified by cannabichromene, which, however, increased oleoylethanolamide levels. In vivo, cannabichromene ameliorated DNBS-induced colonic inflammation, as revealed by histology, immunohistochemistry and myeloperoxidase activity.Conclusion and ImplicationsCannabichromene exerts anti-inflammatory actions in activated macrophages – with tonic CB1 cannabinoid signalling being negatively coupled to this effect – and ameliorates experimental murine colitis.

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KW - cannabinoid receptors

KW - endocannabinoids

KW - inflammatory bowel disease

KW - macrophages

KW - nitric oxide

KW - non-psychotropic cannabinoids

KW - oleoylethanolamide

KW - transient receptor potential (TRP) channels

KW - TRPA1

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