Demethylnobiletin inhibits delayed-type hypersensitivity reactions, human lymphocyte proliferation and cytokine production

Esperanza Bas Infante, M. C. Recio, R. M. Giner, S. Má̃ez, C. López-Ginés, R. Gil-Benso, J. L. Ríos

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Background and purpose: Our aim was to examine the effect of demethylnobiletin on various experimental models of delayed-type hypersensitivity (DTH) reactions and to determine its influence on the mediators and enzymes involved in these reactions. Experimental approach: DTH was induced in mice by oxazolone, dinitrofluorobenzene (DNFB) and sheep red blood cells (SRBC). The effect of demethylnobiletin on the ensuing DTH was studied, especially in relation to oedema formation, cell infiltration and tissue damage. Its activity on different mediators implicated in DTH reactions was also determined and its effect on nitric oxide synthase (NOS)-2 analysed. Finally, its influence on T lymphocyte proliferation, apoptosis and caspase 3 activity was tested. Key results: DTH reactions were all reduced by demethylnobiletin. The experimental results suggest that the compound may act by reducing cell infiltration and by suppressing mediators such as interleukin-2 (IC 50=1.63 μM), interleukin-4 (IC 50=2.76 μM), tumour necrosis factor-α (IC 50=0.66 μM), interferon-γ (IC 50=1.35 μM), and interleukin-1β (46% at 2.5 μM) and by concomitantly increasing the production of the anti-inflammatory cytokine, interleukin-10. In addition, while demethylnobiletin affected nitric oxide production, it did not modify NOS-2 expression. Finally, demethylnobiletin inhibited proliferation of T cells and induced their apoptosis. Conclusions and implications: Demethylnobiletin decreased DTH reactions induced by various agents. This finding, along with the fact that the compound has a low toxicity and exhibits several other interesting properties, could pave the way for other structurally related citroflavonoids to be used as pharmacological agents in complementary therapies.

Original languageEnglish (US)
Pages (from-to)1272-1282
Number of pages11
JournalBritish Journal of Pharmacology
Volume152
Issue number8
DOIs
StatePublished - Dec 2007
Externally publishedYes

Fingerprint

Delayed Hypersensitivity
Lymphocytes
Cytokines
Nitric Oxide Synthase
Oxazolone
Dinitrofluorobenzene
Apoptosis
T-Lymphocytes
Complementary Therapies
Interleukin-1
Caspase 3
Interleukin-4
Interleukin-10
Interferons
Interleukin-2
Edema
Sheep
Nitric Oxide
Anti-Inflammatory Agents
Theoretical Models

Keywords

  • Delayed-type hypersensitivity
  • Demethylnobiletin
  • Interferon
  • Interleukins
  • Lymphocyte proliferation
  • Tumour necrosis factor

ASJC Scopus subject areas

  • Pharmacology

Cite this

Demethylnobiletin inhibits delayed-type hypersensitivity reactions, human lymphocyte proliferation and cytokine production. / Bas Infante, Esperanza; Recio, M. C.; Giner, R. M.; Má̃ez, S.; López-Ginés, C.; Gil-Benso, R.; Ríos, J. L.

In: British Journal of Pharmacology, Vol. 152, No. 8, 12.2007, p. 1272-1282.

Research output: Contribution to journalArticle

Bas Infante, Esperanza ; Recio, M. C. ; Giner, R. M. ; Má̃ez, S. ; López-Ginés, C. ; Gil-Benso, R. ; Ríos, J. L. / Demethylnobiletin inhibits delayed-type hypersensitivity reactions, human lymphocyte proliferation and cytokine production. In: British Journal of Pharmacology. 2007 ; Vol. 152, No. 8. pp. 1272-1282.
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abstract = "Background and purpose: Our aim was to examine the effect of demethylnobiletin on various experimental models of delayed-type hypersensitivity (DTH) reactions and to determine its influence on the mediators and enzymes involved in these reactions. Experimental approach: DTH was induced in mice by oxazolone, dinitrofluorobenzene (DNFB) and sheep red blood cells (SRBC). The effect of demethylnobiletin on the ensuing DTH was studied, especially in relation to oedema formation, cell infiltration and tissue damage. Its activity on different mediators implicated in DTH reactions was also determined and its effect on nitric oxide synthase (NOS)-2 analysed. Finally, its influence on T lymphocyte proliferation, apoptosis and caspase 3 activity was tested. Key results: DTH reactions were all reduced by demethylnobiletin. The experimental results suggest that the compound may act by reducing cell infiltration and by suppressing mediators such as interleukin-2 (IC 50=1.63 μM), interleukin-4 (IC 50=2.76 μM), tumour necrosis factor-α (IC 50=0.66 μM), interferon-γ (IC 50=1.35 μM), and interleukin-1β (46{\%} at 2.5 μM) and by concomitantly increasing the production of the anti-inflammatory cytokine, interleukin-10. In addition, while demethylnobiletin affected nitric oxide production, it did not modify NOS-2 expression. Finally, demethylnobiletin inhibited proliferation of T cells and induced their apoptosis. Conclusions and implications: Demethylnobiletin decreased DTH reactions induced by various agents. This finding, along with the fact that the compound has a low toxicity and exhibits several other interesting properties, could pave the way for other structurally related citroflavonoids to be used as pharmacological agents in complementary therapies.",
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AU - Recio, M. C.

AU - Giner, R. M.

AU - Má̃ez, S.

AU - López-Ginés, C.

AU - Gil-Benso, R.

AU - Ríos, J. L.

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AB - Background and purpose: Our aim was to examine the effect of demethylnobiletin on various experimental models of delayed-type hypersensitivity (DTH) reactions and to determine its influence on the mediators and enzymes involved in these reactions. Experimental approach: DTH was induced in mice by oxazolone, dinitrofluorobenzene (DNFB) and sheep red blood cells (SRBC). The effect of demethylnobiletin on the ensuing DTH was studied, especially in relation to oedema formation, cell infiltration and tissue damage. Its activity on different mediators implicated in DTH reactions was also determined and its effect on nitric oxide synthase (NOS)-2 analysed. Finally, its influence on T lymphocyte proliferation, apoptosis and caspase 3 activity was tested. Key results: DTH reactions were all reduced by demethylnobiletin. The experimental results suggest that the compound may act by reducing cell infiltration and by suppressing mediators such as interleukin-2 (IC 50=1.63 μM), interleukin-4 (IC 50=2.76 μM), tumour necrosis factor-α (IC 50=0.66 μM), interferon-γ (IC 50=1.35 μM), and interleukin-1β (46% at 2.5 μM) and by concomitantly increasing the production of the anti-inflammatory cytokine, interleukin-10. In addition, while demethylnobiletin affected nitric oxide production, it did not modify NOS-2 expression. Finally, demethylnobiletin inhibited proliferation of T cells and induced their apoptosis. Conclusions and implications: Demethylnobiletin decreased DTH reactions induced by various agents. This finding, along with the fact that the compound has a low toxicity and exhibits several other interesting properties, could pave the way for other structurally related citroflavonoids to be used as pharmacological agents in complementary therapies.

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