Novel action of the chalcone isoliquiritigenin as a cystic fibrosis transmembrane conductance regulator (CFTR) inhibitor: Potential therapy for cholera and polycystic kidney disease
Overstimulation of cAMP-activated Cl - secretion can cause secretory diarrhea. Isoliquiritigenin (ISLQ) is a plant-derived chalcone that has a wide range of biological activities. The present study thus aimed to investigate the effect of ISLQ on cAMP-activated Cl - secretion in human intestinal...
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th-mahidol.138022018-06-11T12:24:14Z Novel action of the chalcone isoliquiritigenin as a cystic fibrosis transmembrane conductance regulator (CFTR) inhibitor: Potential therapy for cholera and polycystic kidney disease Chatchai Muanprasat Lalida Sirianant Sunhapas Soodvilai Ratchanaporn Chokchaisiri Apichart Suksamrarn Varanuj Chatsudthipong Mahidol University Ramkhamhaeng University Biochemistry, Genetics and Molecular Biology Pharmacology, Toxicology and Pharmaceutics Overstimulation of cAMP-activated Cl - secretion can cause secretory diarrhea. Isoliquiritigenin (ISLQ) is a plant-derived chalcone that has a wide range of biological activities. The present study thus aimed to investigate the effect of ISLQ on cAMP-activated Cl - secretion in human intestinal epithelium, especially the underlying mechanism and therapeutic application. Short-circuit current analysis of human intestinal epithelial (T84) cell monolayers revealed that ISLQ dose-dependently inhibited cAMP-activated Cl - secretion with an IC50 of approximately 20 μM. ISLQ had no effect on either basal short-circuit current or Ca 2+ -activated Cl - secretion. Apical Cl - current analysis of T84 cell monolayers indicated that ISLQ blocked mainly the cystic fibrosis transmembrane conductance regulator (CFTR) Cl - channels, but not other unidentified cAMPdependent Cl - channels. ISLQ did not affect intracellular cAMP levels or cell viability. ISLQ completely abolished the cholera toxin-induced transepithelial Cl - secretion in T84 cells and reduced the cholera toxin-induced intestinal fluid secretion in mouse closed loop models by 90%. Similarly, ISLQ completely inhibited the cAMP-activated apical Cl - current across monolayers of Madin-Darby Canine Kidney (MDCK) cells and retarded cyst growth in MDCK cyst models by 90%. This study reveals a novel action of ISLQ as a potent CFTR inhibitor with therapeutic potential for treatment of cholera and polycystic kidney disease. © The Japanese Pharmacological Society. 2018-06-11T04:39:20Z 2018-06-11T04:39:20Z 2012-02-08 Article Journal of Pharmacological Sciences. Vol.118, No.1 (2012), 82-91 10.1254/jphs.11153FP 13478648 13478613 2-s2.0-84856570690 https://repository.li.mahidol.ac.th/handle/123456789/13802 Mahidol University SCOPUS https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=84856570690&origin=inward |
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Biochemistry, Genetics and Molecular Biology Pharmacology, Toxicology and Pharmaceutics Chatchai Muanprasat Lalida Sirianant Sunhapas Soodvilai Ratchanaporn Chokchaisiri Apichart Suksamrarn Varanuj Chatsudthipong Novel action of the chalcone isoliquiritigenin as a cystic fibrosis transmembrane conductance regulator (CFTR) inhibitor: Potential therapy for cholera and polycystic kidney disease |
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Overstimulation of cAMP-activated Cl - secretion can cause secretory diarrhea. Isoliquiritigenin (ISLQ) is a plant-derived chalcone that has a wide range of biological activities. The present study thus aimed to investigate the effect of ISLQ on cAMP-activated Cl - secretion in human intestinal epithelium, especially the underlying mechanism and therapeutic application. Short-circuit current analysis of human intestinal epithelial (T84) cell monolayers revealed that ISLQ dose-dependently inhibited cAMP-activated Cl - secretion with an IC50 of approximately 20 μM. ISLQ had no effect on either basal short-circuit current or Ca 2+ -activated Cl - secretion. Apical Cl - current analysis of T84 cell monolayers indicated that ISLQ blocked mainly the cystic fibrosis transmembrane conductance regulator (CFTR) Cl - channels, but not other unidentified cAMPdependent Cl - channels. ISLQ did not affect intracellular cAMP levels or cell viability. ISLQ completely abolished the cholera toxin-induced transepithelial Cl - secretion in T84 cells and reduced the cholera toxin-induced intestinal fluid secretion in mouse closed loop models by 90%. Similarly, ISLQ completely inhibited the cAMP-activated apical Cl - current across monolayers of Madin-Darby Canine Kidney (MDCK) cells and retarded cyst growth in MDCK cyst models by 90%. This study reveals a novel action of ISLQ as a potent CFTR inhibitor with therapeutic potential for treatment of cholera and polycystic kidney disease. © The Japanese Pharmacological Society. |
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Mahidol University |
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Mahidol University Chatchai Muanprasat Lalida Sirianant Sunhapas Soodvilai Ratchanaporn Chokchaisiri Apichart Suksamrarn Varanuj Chatsudthipong |
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Chatchai Muanprasat Lalida Sirianant Sunhapas Soodvilai Ratchanaporn Chokchaisiri Apichart Suksamrarn Varanuj Chatsudthipong |
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Chatchai Muanprasat |
title |
Novel action of the chalcone isoliquiritigenin as a cystic fibrosis transmembrane conductance regulator (CFTR) inhibitor: Potential therapy for cholera and polycystic kidney disease |
title_short |
Novel action of the chalcone isoliquiritigenin as a cystic fibrosis transmembrane conductance regulator (CFTR) inhibitor: Potential therapy for cholera and polycystic kidney disease |
title_full |
Novel action of the chalcone isoliquiritigenin as a cystic fibrosis transmembrane conductance regulator (CFTR) inhibitor: Potential therapy for cholera and polycystic kidney disease |
title_fullStr |
Novel action of the chalcone isoliquiritigenin as a cystic fibrosis transmembrane conductance regulator (CFTR) inhibitor: Potential therapy for cholera and polycystic kidney disease |
title_full_unstemmed |
Novel action of the chalcone isoliquiritigenin as a cystic fibrosis transmembrane conductance regulator (CFTR) inhibitor: Potential therapy for cholera and polycystic kidney disease |
title_sort |
novel action of the chalcone isoliquiritigenin as a cystic fibrosis transmembrane conductance regulator (cftr) inhibitor: potential therapy for cholera and polycystic kidney disease |
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2018 |
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https://repository.li.mahidol.ac.th/handle/123456789/13802 |
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1763492552309211136 |