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...
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Elsevier,
2012-01-01T00:00:00Z.
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| 001 | doaj_688f32689ee945d4ac7a6ac7abd6bb2c | ||
| 042 | |a dc | ||
| 100 | 1 | 0 | |a Chatchai Muanprasat |e author |
| 700 | 1 | 0 | |a Lalida Sirianant |e author |
| 700 | 1 | 0 | |a Sunhapas Soodvilai |e author |
| 700 | 1 | 0 | |a Ratchanaporn Chokchaisiri |e author |
| 700 | 1 | 0 | |a Apichart Suksamrarn |e author |
| 700 | 1 | 0 | |a Varanuj Chatsudthipong |e author |
| 245 | 0 | 0 | |a Novel Action of the Chalcone Isoliquiritigenin as a Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Inhibitor: Potential Therapy for Cholera and Polycystic Kidney Disease |
| 260 | |b Elsevier, |c 2012-01-01T00:00:00Z. | ||
| 500 | |a 1347-8613 | ||
| 500 | |a 10.1254/jphs.11153FP | ||
| 520 | |a 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 | ||
| 546 | |a EN | ||
| 690 | |a Therapeutics. Pharmacology | ||
| 690 | |a RM1-950 | ||
| 655 | 7 | |a article |2 local | |
| 786 | 0 | |n Journal of Pharmacological Sciences, Vol 118, Iss 1, Pp 82-91 (2012) | |
| 787 | 0 | |n http://www.sciencedirect.com/science/article/pii/S1347861319306012 | |
| 787 | 0 | |n https://doaj.org/toc/1347-8613 | |
| 856 | 4 | 1 | |u https://doaj.org/article/688f32689ee945d4ac7a6ac7abd6bb2c |z Connect to this object online. |