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
References
Feb 20, 1992·The New England Journal of Medicine·W O SpitzerA S Rebuck
Nov 17, 1998·American Journal of Respiratory and Critical Care Medicine·M Johnson
Mar 10, 1999·The American Journal of Physiology·K HottaC A Hirshman
Apr 22, 1999·General Pharmacology·L Gamet-PayrastreB Payrastre
Mar 17, 2001·The Journal of Physiology·A V ShmigolS Wray
Aug 28, 2002·The Journal of Pharmacy and Pharmacology·Raffaele Capasso, Ignatius A Tavares
Feb 18, 2003·Fundamental & Clinical Pharmacology·M T KhayyalM M Khattab
Aug 20, 2003·The Journal of Clinical Investigation·Dennis W McGrawStephen B Liggett
May 19, 2004·Annals of Internal Medicine·Shelley R SalpeterEdwin E Salpeter
Sep 20, 2005·Life Sciences·Silvana MorelloCarla Cicala
Jan 21, 2006·Chest·Harold S NelsonUNKNOWN SMART Study Group
Apr 18, 2006·American Journal of Physiology. Lung Cellular and Molecular Physiology·Reinoud GosensAndrew J Halayko
Nov 3, 2006·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Hyo-Hyun ParkSang-Hyun Kim
May 15, 2007·Current Topics in Developmental Biology·Vera P Krymskaya, Reynold A Panettieri
Jan 22, 2008·American Journal of Physiology. Lung Cellular and Molecular Physiology·Kentaro MizutaCharles W Emala
Oct 26, 2011·Pediatrics·Ann W McMahonDianne Murphy
Apr 18, 2012·Pharmacology·Min WenHaitao Zhang
Oct 16, 2012·American Journal of Respiratory Cell and Molecular Biology·Elizabeth A TownsendCharles W Emala
Mar 29, 2013·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·Hui-Hun KimSang-Hyun Kim
May 10, 2013·American Journal of Respiratory and Critical Care Medicine·Bianca BeghèLeonardo M Fabbri
Jun 14, 2013·Evidence-based Complementary and Alternative Medicine : ECAM·Wang-Jian ZhaMao Huang
Jul 23, 2013·American Journal of Physiology. Lung Cellular and Molecular Physiology·Elizabeth A Townsend, Charles W Emala
Apr 20, 2014·Inflammation·Yu-Sheng ShuYa-Bing Zhu
Feb 13, 2015·Molecular Medicine Reports·Yuan-Hua LiuChun-Tao Liu
Jul 17, 2015·Anesthesiology·Jennifer DanielssonCharles W Emala
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
Feb 19, 2019·Frontiers in Pharmacology·Manish Bodas, Neeraj Vij
Oct 23, 2018·BioMed Research International·Zhiqiang PangFang Wang
Apr 30, 2019·Frontiers in Pharmacology·Shan RanYanquan Han