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Eur J Nutr. 2017 Jun;56(4):1609-1620. doi: 10.1007/s00394-016-1207-z. Epub 2016 Mar 28.

Citrus peel polymethoxyflavones nobiletin and tangeretin suppress LPS- and IgE-mediated activation of human intestinal mast cells.

Author information

1
Department of Nutritional Medicine, University of Hohenheim, Fruwirthstraße 12, 70593, Stuttgart, Germany.
2
Clinic for Visceral Surgery, Katharinenhospital, Kriegsbergstraße 60, 70174, Stuttgart, Germany.
3
Department of General, Visceral, and Thorax Surgery, Marienhospital, Böheimstraße 37, 70199, Stuttgart, Germany.
4
Department of Nutritional Medicine, University of Hohenheim, Fruwirthstraße 12, 70593, Stuttgart, Germany. Lorentz@uni-hohenheim.de.

Abstract

PURPOSE:

Allergic diseases with mast cells (MC) as main effector cells show an increased prevalence. MC also play an essential role in other inflammatory conditions. Therapeutical use of anti-inflammatory nutraceuticals directly targeting MC activation could be of interest for afflicted patients. Nobiletin and tangeretin are citrus peel polymethoxyflavones, a group of citrus flavonoids, possessing anticancer, antimetastatic, and anti-inflammatory activities. Here, we analyzed the effects of nobiletin/tangeretin on LPS- and IgE-mediated stimulation of human intestinal mast cells (hiMC).

METHODS:

MC isolated from human intestinal tissue were treated with different concentrations of nobiletin or tangeretin prior to stimulation via LPS/sCD14 or IgE-dependently. Degranulation, pro-inflammatory cytokine expression and phosphorylation of ERK1/2 were examined.

RESULTS:

Expression of CXCL8, CCL3, CCL4 and IL-1β in response to LPS-mediated stimulation was inhibited by nobiletin/tangeretin. hiMC activated IgE-dependently showed a reduced release of β-hexosaminidase and cysteinyl LTC4 in response to nobiletin, but not in response to tangeretin. Expression of CXCL8, CCL2, CCL3, CCL4 and TNF in IgE-dependently activated hiMC was decreased in a dose-dependent manner following treatment with nobiletin/tangeretin. IL-1β expression was only reduced by tangeretin. Compared to treatment with NF-κB inhibitor BMS345541 or MEK-inhibitor PD98059, nobiletin and tangeretin showed similar effects on mediator production. Phosphorylation of ERK1/2 upon IgE-mediated antigen stimulation was significantly suppressed by nobiletin and tangeretin.

CONCLUSIONS:

Nobiletin and, to a lesser extent, tangeretin could be considered as anti-inflammatory nutraceuticals by reducing release and production of proinflammatory mediators in MC.

KEYWORDS:

Allergy; Citrus fruits; Flavonoids; Mast cells; Nutraceuticals

PMID:
27021766
DOI:
10.1007/s00394-016-1207-z
[Indexed for MEDLINE]

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