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 epithe...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2012-01-01
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| Series: | Journal of Pharmacological Sciences |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1347861319306012 |
| _version_ | 1818204464707796992 |
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| author | Chatchai Muanprasat Lalida Sirianant Sunhapas Soodvilai Ratchanaporn Chokchaisiri Apichart Suksamrarn Varanuj Chatsudthipong |
| author_facet | Chatchai Muanprasat Lalida Sirianant Sunhapas Soodvilai Ratchanaporn Chokchaisiri Apichart Suksamrarn Varanuj Chatsudthipong |
| author_sort | Chatchai Muanprasat |
| collection | DOAJ |
| description | 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 Ca2+-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 cAMP-dependent 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. Keywords:: isoliquiritigenin, chalcone, cystic fibrosis transmembrane conductance regulator (CFTR), cholera, polycystic kidney disease |
| first_indexed | 2024-12-12T03:41:39Z |
| format | Article |
| id | doaj.art-688f32689ee945d4ac7a6ac7abd6bb2c |
| institution | Directory Open Access Journal |
| issn | 1347-8613 |
| language | English |
| last_indexed | 2024-12-12T03:41:39Z |
| publishDate | 2012-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Pharmacological Sciences |
| spelling | doaj.art-688f32689ee945d4ac7a6ac7abd6bb2c2022-12-22T00:39:40ZengElsevierJournal of Pharmacological Sciences1347-86132012-01-0111818291Novel Action of the Chalcone Isoliquiritigenin as a Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Inhibitor: Potential Therapy for Cholera and Polycystic Kidney DiseaseChatchai Muanprasat0Lalida Sirianant1Sunhapas Soodvilai2Ratchanaporn Chokchaisiri3Apichart Suksamrarn4Varanuj Chatsudthipong5Department of Physiology and Bangkok 10400, Thailand; Corresponding author. scchatchai@mahidol.ac.thGraduate Program in Toxicology, Faculty of Science, Mahidol University, Bangkok 10400, ThailandDepartment of Physiology and Bangkok 10400, ThailandDepartment of Chemistry, Faculty of Science, Ramkamhaeng University, Bangkok 10240, ThailandDepartment of Chemistry, Faculty of Science, Ramkamhaeng University, Bangkok 10240, ThailandDepartment of Physiology and Bangkok 10400, ThailandOverstimulation 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 Ca2+-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 cAMP-dependent 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. Keywords:: isoliquiritigenin, chalcone, cystic fibrosis transmembrane conductance regulator (CFTR), cholera, polycystic kidney diseasehttp://www.sciencedirect.com/science/article/pii/S1347861319306012 |
| spellingShingle | 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 Journal of Pharmacological Sciences |
| 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_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_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_sort | novel action of the chalcone isoliquiritigenin as a cystic fibrosis transmembrane conductance regulator cftr inhibitor potential therapy for cholera and polycystic kidney disease |
| url | http://www.sciencedirect.com/science/article/pii/S1347861319306012 |
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