Quercetin acutely relaxes airway smooth muscle and potentiates β-agonist-induced relaxation via dual phosphodiesterase inhibition of PLCβ and PDE4
TLDR
Novel data show that the natural PDE4-selective inhibitor quercetin may provide therapeutic relief of asthma symptoms and decrease reliance on short-acting β-agonists.Abstract:
Asthma is a disease of the airways with symptoms including exaggerated airway narrowing and airway inflammation. Early asthma therapies used methylxanthines to relieve symptoms, in part, by inhibiting cyclic nucleotide phosphodiesterases (PDEs), the enzyme responsible for degrading cAMP. The classification of tissue-specific PDE subtypes and the clinical introduction of PDE-selective inhibitors for chronic obstructive pulmonary disease (i.e., roflumilast) have reopened the possibility of using PDE inhibition in the treatment of asthma. Quercetin is a naturally derived PDE4-selective inhibitor found in fruits, vegetables, and tea. We hypothesized that quercetin relaxes airway smooth muscle via cAMP-mediated pathways and augments β-agonist relaxation. Tracheal rings from male A/J mice were mounted in myographs and contracted with acetylcholine (ACh). Addition of quercetin (100 nM-1 mM) acutely and concentration-dependently relaxed airway rings precontracted with ACh. In separate studies, pretreatment with quercetin (100 μM) prevented force generation upon exposure to ACh. In additional studies, quercetin (50 μM) significantly potentiated isoproterenol-induced relaxations. In in vitro assays, quercetin directly attenuated phospholipase C activity, decreased inositol phosphate synthesis, and decreased intracellular calcium responses to Gq-coupled agonists (histamine or bradykinin). Finally, nebulization of quercetin (100 μM) in an in vivo model of airway responsiveness significantly attenuated methacholine-induced increases in airway resistance. These novel data show that the natural PDE4-selective inhibitor quercetin may provide therapeutic relief of asthma symptoms and decrease reliance on short-acting β-agonists.read more
Citations
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Quercetin and Its Anti-Allergic Immune Response
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Airway smooth muscle in airway reactivity and remodeling: what have we learned?
TL;DR: This perspective highlights recent discoveries that reveal the central role of ASM in this regard and helps set the stage for future research toward understanding the pathways regulating ASM and, in turn, the influence of ASm on airway structure and function.
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Structure-Activity Association of Flavonoids in Lung Diseases
João Henrique G. Lago,Alessandra Choqueta de Toledo-Arruda,Marcia Mernak,Kaidu H. Barrosa,Milton A. Martins,Iolanda F.L.C. Tibério,Carla Máximo Prado +6 more
TL;DR: The effects of different flavonoids in the control of lung inflammation in some disorders such as asthma, lung emphysema and acute respiratory distress syndrome are discussed and some structure-activity relationships between this biological potential and chemical profile of these compounds are established.
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A minireview of quercetin: from its metabolism to possible mechanisms of its biological activities
Hande Gül Ulusoy,Nevin Sanlier +1 more
TL;DR: Quercetin is known as an antioxidant, anti-inflammatory, cardioprotective, and anti-obesity compound, thought to be beneficial against cardiovascular diseases, cancer, diabetes, neurological diseases, obesity, allergy asthma, and atopic diseases.
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Emerging concepts in smooth muscle contributions to airway structure and function: implications for health and disease
TL;DR: This review emphasizes established and recent discoveries that underline the central role of ASM and sets the stage for future research toward understanding how ASM plays a central role by being both upstream and downstream in the many interactive processes that determine airway structure and function in health and disease.
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