Suppression of neuropeptide production by quercetin in allergic rhinitis model rats.

BACKGROUND: Quercetin, a dietary flavonoid found in many fruits, red wine and onion, among others, has been reported to have potent anti-oxidant, anti-viral and anti-cancer effects. Although quercetin is also reported to have anti-inflammatory and anti-allergic effects, the precise mechanisms by which quercetin favorably modify the clinical conditions of allergic diseases such as allergic rhinitis (AR). The present study was designed to examine the influence of quercetin on the development of AR by using AR model rats. METHODS: Sprague-Dawley (SD) rats were sensitized with toluene 2,4-diisocyanate (TDI) by intranasal instillation of a 10 % TDI in ethyl acetate in a volume of 5 µl once a day for 5 consecutive days. This sensitization procedure was repeated after a 2-day interval. After 5 days of the second sensitization, rats were treated with various doses of quercetin once a day for 2 to 7 days. Nasal allergy-like symptoms, which were induced by bilateral application of 5 µl of 10 % TDI in ethyl acetate, were assessed by counting sneezing and nasal rubbing behaviors for 10 min just after TDI nasal challenge. The levels of substance P (SP), calcitonin gene-related peptide (CGRP) and nerve growth factor (NGF) in nasal lavage fluids obtained 6 h after TDI nasal challenge was examined by ELISA. RESULTS: Oral administration of quercetin for 5 and 7 days, but not 2 and 3 days, could inhibit sneezing and nasal rubbing movements, which were increased by TDI nasal challenge. The minimum dose that caused significant inhibition was 25 mg/kg. Oral administration of quercetin at more than 25 mg/kg for 5 days significantly inhibited the increase in SP, CGRP and NGF contents in nasal lavage fluids induced by TDI nasal challenge. CONCLUSION: The present results strongly suggested that quercetin will be a good candidate for the supplement on the management and treatment of allergic diseases, especially AR.

Suppressive Activity of Quercetin on Periostin Functions In Vitro.

Periostin, a 90-kDa extracellular matrix protein, has been attracting attention as a novel biomarker of airway inflammatory diseases such as allergic rhinitis (AR) and asthma. Although oral administration of quercetin to patients with AR can favorably modify the clinical condition of this disease, the influence of quercetin on periostin functions is not well understood. The present study was, therefore, undertaken to examine the influence of quercetin on the production of both periostin and periostin-induced eosinophil chemoattractants from human nasal epithelial cells (HNEpC) in vitro. HNEpC were stimulated with 15.0 ng/ml interleukin (IL)-4 in the absence or presence of quercetin for 72 h. Periostin levels in the culture supernatants were measured using enzyme-linked immunosorbent assay (ELISA). Addition of 4.0 µM quercetin into cell cultures suppressed periostin production from HNEpC that was induced by IL-4 stimulation through inhibitation of signal transducer and activator of transcription 6 (STAT6) activation. We then examined whether quercetin could inhibit production of the periostin-induced eosinophil chemoattractants, regulated on activation, normal T-cell expressed and secreted (RANTES) and eotaxin, from HNEpC. HNEpC were stimulated with 2.0 ng/ml periostin in the absence or presence of quercetin for 72 h. RANTES and eotaxin levels in culture supernatants were examined using ELISA. Treatment of HNEpC with quercetin at a concentration of 4.0 µM suppressed the ability of cells to produce RANTES and eotaxin. This suppression was mediated through suppression of activation of the transcription factor nuclear factor-kappa B (NF-κB) p65, as measured using ELISA, and of chemokine mRNA expression, as measured using reverse transcriptase-polymerase chain reaction (RT-PCR). These results strongly suggest that quercetin suppresses the production of both periostin and periostin-induced eosinophil chemoattractants from HNEpC and results in improvement of the clinical condition of AR.

Suppressive activity of quercetin on the production of eosinophil chemoattractants from eosinophils in vitro.

Quercetin, a flavonoid found in a wide variety of plants, has been studied for possible health benefits, and it has been found to have potent anti-oxidant, anti-viral and anticancer effects. Although quercetin is also reported to act as an antihistamine and an anti-inflammatory through the suppression of mast cell activation, the influence of quercetin on eosinophil activation is not fully understood. The present study, therefore, was undertaken to examine the influence of quercetin on eosinophil activation, especially chemokine production by using an in vitro cell culture technique. Eosinophils (5×10(5) cells/ml) obtained from Mesocestoides corti-infected mice were stimulated with 200 ng/ml stem cell factor in the presence of different concentrations of quercetin for 24 h. Chemokine, eotaxin, regulated on activation normal T cell expressed and secreted and macrophage inflammatory protein-1ß, levels in culture supernatants were examined by enzyme-linked immunosorbent assay (ELISA). We also examined the influence of quercetin on chemokine mRNA expression and transcription factor, nuclear factor kappa B and activator protein 1, activation by real-time reverse transcription polymerase chain reaction and ELISA, respectively. Treatment of eosinophils with quercetin at more than 4.5 µM caused a significant decrease in chemokine levels in culture supernatants. Quercetin also suppressed transcription factor activation in 4 h-cultured cells and mRNA expression of chemokine in 12 h-cultured cells, which were increased by stem cell factor stimulation. These results may suggest that quercetin inhibits eosinophil activation, especially chemokine production, and results in inhibition of the development of eosinophilic inflammatory responses.

Inhibitory action of quercetin on eosinophil activation in vitro.

The influence of quercetin on eosinophil functions was examined in vitro and in vivo. The first set of experiments was undertaken to examine whether quercetin could suppress eosinophilia and IgE hyperproduction induced by Mesocestoides corti infection in BALB/c mice. The number of peripheral blood eosinophils and IgE levels were examined 21 days after infection. Oral administration of quercetin for 21 days could not suppress both peripheral blood eosinophilia and IgE hyperproduction, even when 20.0 mg/kg quercetin was used for treatment. The second part of the experiment was designed to examine the influence of quercetin on eosinophil activation induced by SCF stimulation in vitro. Eosinophils were obtained from M. corti-infected mice and stimulated with SCF in the presence of various concentrations of quercetin for 24 h. The addition of quercetin into cell cultures could suppress eosinophil activation induced by SCF stimulation as assessed by measuring the contents of RANTES, MIP-1 ß , ECP, and MBP in culture supernatants. The minimum concentration of quercetin which caused significant suppression of factor secretion was 5.0 µ M. These results may suggest that quercetin will be a good candidate for the supplement on the management of eosinophil-mediated diseases, such as allergic rhinitis and asthma.