Attenuation of airway smooth muscle contractility via flavonol-mediated inhibition of phospholipase-Cβ

American Journal of Physiology. Lung Cellular and Molecular Physiology
Amy BrownGeorge Gallos

Abstract

Enhanced contractility of airway smooth muscle (ASM) is a major pathophysiological characteristic of asthma. Expanding the therapeutic armamentarium beyond β-agonists that target ASM hypercontractility would substantially improve treatment options. Recent studies have identified naturally occurring phytochemicals as candidates for acute ASM relaxation. Several flavonoids were evaluated for their ability to acutely relax human and murine ASM ex vivo and murine airways in vivo and were evaluated for their ability to inhibit procontractile signaling pathways in human ASM (hASM) cells. Two members of the flavonol subfamily, galangin and fisetin, significantly relaxed acetylcholine-precontracted murine tracheal rings ex vivo (n = 4 and n = 5, respectively, P < 0.001). Galangin and fisetin also relaxed acetylcholine-precontracted hASM strips ex vivo (n = 6-8, P < 0.001). Functional respiratory in vivo murine studies demonstrated that inhaled galangin attenuated the increase in lung resistance induced by inhaled methacholine (n = 6, P < 0.01). Both flavonols, galangin and fisetin, significantly inhibited purified phosphodiesterase-4 (PDE4) (n = 7, P < 0.05; n = 7, P < 0.05, respectively), and PLCβ enzymes (n = 6, P < 0.001 and n = 6, ...Continue Reading

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Citations

Oct 16, 2016·American Journal of Physiology. Lung Cellular and Molecular Physiology·Y S Prakash
Dec 12, 2019·Critical Reviews in Food Science and Nutrition·Dinh-Chuong PhamBharath Kumar Velmurugan
Mar 27, 2020·American Journal of Physiology. Lung Cellular and Molecular Physiology·Kentaro MizutaCharles W Emala

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