Demethylnobiletin inhibits delayed-type hypersensitivity reactions, human lymphocyte proliferation and cytokine production
Article first published online: 29 JAN 2009
2007 British Pharmacological Society
British Journal of Pharmacology
Volume 152, Issue 8, pages 1272–1282, December 2007
How to Cite
Bas, E., Recio, M. C., Giner, R. M., Máñez, S., López-Ginés, C., Gil-Benso, R. and Ríos, J. L. (2007), Demethylnobiletin inhibits delayed-type hypersensitivity reactions, human lymphocyte proliferation and cytokine production. British Journal of Pharmacology, 152: 1272–1282. doi: 10.1038/sj.bjp.0707500
- Issue published online: 29 JAN 2009
- Article first published online: 29 JAN 2009
- (Received June 11, 2007, Revised July 24, 2007, Accepted August 2, 2007)
- delayed-type hypersensitivity;
- lymphocyte proliferation;
- tumour necrosis factor;
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.
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.
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 (IC50=1.63 μM), interleukin-4 (IC50=2.76 μM), tumour necrosis factor-α (IC50=0.66 μM), interferon-γ (IC50=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.
British Journal of Pharmacology (2007) 152, 1272–1282; doi:10.1038/sj.bjp.0707500; published online 15 October 2007