Bimodal action of the flavonoid quercetin on basophil function: an investigation of the putative biochemical targets

Quercetin inhibited the expression of CD63 and CD203c and the histamine release in basophils activated with anti-IgE or with the ionophore: the IC50 in the anti-IgE model was higher than in the ionophore model and the effects were more pronounced for CD63 than for CD203c. Nanomolar concentrations of quercetin were able to prime both markers expression and histamine release in the fMLP activation model while no effect of quercetin was observed when basophils were activated with PMA. The specific phosphoinositide-3 kinase (PI3K) inhibitor wortmannin exhibited the same behavior of quercetin in anti-IgE and fMLP activation, thus suggesting a role for PI3K involvement in the priming mechanism.These results rule out a possible role of protein kinase C in the complex response of basophil to quercetin, while indirectly suggest PI3K as the major intracellular target of this compound also in human basophils.Flavonoids include a large group of low molecular weight polyphenolic secondary plant metabolites which can be found in fruits and vegetables, and plant derived beverages such as tea, wine and coffee [1-3]. More recently, these natural compounds have been recognized to exert antioxidant [4], anti-bacterial and anti-viral activity, in addition to anti-allergic effects [5-7], and exert anti-inflammatory [8], anti-angiogenic, analgesic, cardiovascular-protective [9], anti-hypertensive [10], hepatoprotective [11], cytostatic, cancer preventive [12], apoptotic [13], estrogenic and even anti-estrogenic properties [14]. Quercetin (2-(3,4- dihydroxyphenyl)- 3,5,7- trihydroxy- 4H- chromen- 4-one) is the most abundant of the flavonoids and is commonly used as a food supplement [15], but evidence-based data regarding its clinical efficacy are quite scanty [16]. As well as many other flavonols, quercetin exerts many effects on inflammation and allergic responses. In this context quercetin is known mainly as a strong inhibitor of many effector functions of leukocytes and mast cells at