Isorhamnetin Ameliorates Dry Eye Disease via CFTR Activation in Mice
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 targ...
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MDPI AG
2021-04-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/8/3954 |
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| author | Ho K. Lee Jinhong Park Bo-Rahm Kim Ikhyun Jun Tae-im Kim Wan Namkung |
| author_facet | Ho K. Lee Jinhong Park Bo-Rahm Kim Ikhyun Jun Tae-im Kim Wan Namkung |
| author_sort | Ho K. Lee |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-10T12:24:57Z |
| format | Article |
| id | doaj.art-42c6d522f21f4b5194bbce7cec3dd630 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T12:24:57Z |
| publishDate | 2021-04-01 |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-42c6d522f21f4b5194bbce7cec3dd6302023-11-21T15:08:14ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-04-01228395410.3390/ijms22083954Isorhamnetin Ameliorates Dry Eye Disease via CFTR Activation in MiceHo K. Lee0Jinhong Park1Bo-Rahm Kim2Ikhyun Jun3Tae-im Kim4Wan Namkung5College of Pharmacy and Yonsei Institute of Pharmaceutical Sciences, Yonsei University, 85 Songdogwahak-ro, Yeonsu-gu, Incheon 21983, KoreaCollege of Pharmacy and Yonsei Institute of Pharmaceutical Sciences, Yonsei University, 85 Songdogwahak-ro, Yeonsu-gu, Incheon 21983, KoreaDepartment of Ophthalmology, College of Medicine, Yonsei University, 50 Yonsei-ro, Seodaemoon-Gu, Seoul 03722, KoreaDepartment of Ophthalmology, College of Medicine, Yonsei University, 50 Yonsei-ro, Seodaemoon-Gu, Seoul 03722, KoreaDepartment of Ophthalmology, College of Medicine, Yonsei University, 50 Yonsei-ro, Seodaemoon-Gu, Seoul 03722, KoreaCollege of Pharmacy and Yonsei Institute of Pharmaceutical Sciences, Yonsei University, 85 Songdogwahak-ro, Yeonsu-gu, Incheon 21983, KoreaDry 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.https://www.mdpi.com/1422-0067/22/8/3954isorhamnetincystic fibrosis transmembrane conductance regulatordry eye |
| spellingShingle | Ho K. Lee Jinhong Park Bo-Rahm Kim Ikhyun Jun Tae-im Kim Wan Namkung Isorhamnetin Ameliorates Dry Eye Disease via CFTR Activation in Mice International Journal of Molecular Sciences isorhamnetin cystic fibrosis transmembrane conductance regulator dry eye |
| title | Isorhamnetin Ameliorates Dry Eye Disease via CFTR Activation in Mice |
| title_full | Isorhamnetin Ameliorates Dry Eye Disease via CFTR Activation in Mice |
| title_fullStr | Isorhamnetin Ameliorates Dry Eye Disease via CFTR Activation in Mice |
| title_full_unstemmed | Isorhamnetin Ameliorates Dry Eye Disease via CFTR Activation in Mice |
| title_short | Isorhamnetin Ameliorates Dry Eye Disease via CFTR Activation in Mice |
| title_sort | isorhamnetin ameliorates dry eye disease via cftr activation in mice |
| topic | isorhamnetin cystic fibrosis transmembrane conductance regulator dry eye |
| url | https://www.mdpi.com/1422-0067/22/8/3954 |
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