Isorhamnetin Ameliorates Dry Eye Disease via CFTR Activation in Mice
| Autor: | Tae Im Kim, Jinhong Park, Ho K. Lee, Ikhyun Jun, Bo Rahm Kim, Wan Namkung |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Epithelial sodium channel congenital hereditary and neonatal diseases and abnormalities hERG Interleukin-1beta Pharmacology Catalysis Article Inorganic Chemistry ANO1 lcsh:Chemistry 03 medical and health sciences chemistry.chemical_compound Mice dry eye 0302 clinical medicine Animals Humans Physical and Theoretical Chemistry Molecular Biology lcsh:QH301-705.5 Spectroscopy Isorhamnetin biology Tumor Necrosis Factor-alpha cystic fibrosis transmembrane conductance regulator Organic Chemistry Interleukin-8 Wild type Interleukin Epithelial Cells General Medicine Cystic fibrosis transmembrane conductance regulator eye diseases Computer Science Applications Disease Models Animal 030104 developmental biology chemistry lcsh:Biology (General) lcsh:QD1-999 Gene Expression Regulation isorhamnetin 030221 ophthalmology & optometry biology.protein Tumor necrosis factor alpha Dry Eye Syndromes Quercetin |
| Zdroj: | International Journal of Molecular Sciences Volume 22 Issue 8 International Journal of Molecular Sciences, Vol 22, Iss 3954, p 3954 (2021) |
| ISSN: | 1422-0067 |
| DOI: | 10.3390/ijms22083954 |
| Popis: | Dry eye disease is one of the most common diseases, with increasing prevalence in many countries, but treatment options are limited. Cystic fibrosis transmembrane conductance regulator (CFTR) is a major ion channel that facilitates fluid secretion in ocular surface epithelium and is a potential target of therapeutic agent for the treatment of dry eye disease. In this study, we performed a cell-based, high-throughput screening for the identification of novel natural products that activate CFTR and restore the aqueous deficiency in dry eye. Screening of 1000 natural products revealed isorhamnetin, a flavonol aglycone, as a novel CFTR activator. Electrophysiological studies showed that isorhamnetin significantly increased CFTR chloride current, both wild type and ∆F508-CFTR. Isorhamnetin did not alter intracellular cAMP levels and the activity of other ion channels, including ANO1, ENaC, and hERG. Notably, application of isorhamnetin on mouse ocular surface induced CFTR activation and increased tear volume. In addition, isorhamnetin significantly reduced ocular surface damage and expression of interleukin (IL)-1β, IL-8, and tumor necrosis factor (TNF)-α in an experimental mouse model of dry eye. These data suggest that isorhamnetin may be used to treat dry eye disease. |
| Databáze: | OpenAIRE |
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