ReferenceID 4394
Isorhamnetin Ameliorates Dry Eye Disease via CFTR Activation in Mice
Int J Mol Sci
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
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- Reference Id
- 4394
- Evidence Id
- 20984
- Core Evidence Id
- 20984
- Source Reference Id
- 2073
- Herb2 Reference Id
- HBREF002870
- Subject Paper Key
- HBIN008965_33921231
- Pubmed Id
- 33921231
- Doi
- 10.3390/ijms22083954
- Paper Title
- Isorhamnetin Ameliorates Dry Eye Disease via CFTR Activation in Mice
- Paper Abstract
- 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)-1beta, IL-8, and tumor necrosis factor (TNF)-alpha in an experimental mouse model of dry eye. These data suggest that isorhamnetin may be used to treat dry eye disease.
- Journal
- Int J Mol Sci
- Publish Year
- 2021
- Experiment Subject
- mouse
- Experiment Type
- Animal Experiment
- Phenotype Related
- Tumor; Cystic Fibrosis; Dry Eye Disease; Dry Eye; Aqueous Deficiency
- Paper Title Cn
- Paper Title En
- Isorhamnetin Ameliorates Dry Eye Disease via CFTR Activation in Mice
- Bilingual Status
- semi_complete