{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T05:59:53Z","timestamp":1783490393200,"version":"3.55.0"},"reference-count":48,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2021,4,12]],"date-time":"2021-04-12T00:00:00Z","timestamp":1618185600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2015R1D1A1A01057695"],"award-info":[{"award-number":["2015R1D1A1A01057695"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2018R1A6A1A03023718"],"award-info":[{"award-number":["2018R1A6A1A03023718"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2017R1A6A3A11031453"],"award-info":[{"award-number":["2017R1A6A3A11031453"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2020R1C1C1008332"],"award-info":[{"award-number":["2020R1C1C1008332"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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 \u2206F508-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)-1\u03b2, IL-8, and tumor necrosis factor (TNF)-\u03b1 in an experimental mouse model of dry eye. These data suggest that isorhamnetin may be used to treat dry eye disease.<\/jats:p>","DOI":"10.3390\/ijms22083954","type":"journal-article","created":{"date-parts":[[2021,4,12]],"date-time":"2021-04-12T03:04:06Z","timestamp":1618196646000},"page":"3954","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Isorhamnetin Ameliorates Dry Eye Disease via CFTR Activation in Mice"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1707-3217","authenticated-orcid":false,"given":"Ho K.","family":"Lee","sequence":"first","affiliation":[{"name":"College of Pharmacy and Yonsei Institute of Pharmaceutical Sciences, Yonsei University, 85 Songdogwahak-ro, Yeonsu-gu, Incheon 21983, Korea"},{"name":"Interdisciplinary Program of Integrated OMICS for Biomedical Science Graduate School, Yonsei University, Seoul 03722, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinhong","family":"Park","sequence":"additional","affiliation":[{"name":"College of Pharmacy and Yonsei Institute of Pharmaceutical Sciences, Yonsei University, 85 Songdogwahak-ro, Yeonsu-gu, Incheon 21983, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo-Rahm","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, College of Medicine, Yonsei University, 50 Yonsei-ro, Seodaemoon-Gu, Seoul 03722, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2160-1679","authenticated-orcid":false,"given":"Ikhyun","family":"Jun","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, College of Medicine, Yonsei University, 50 Yonsei-ro, Seodaemoon-Gu, Seoul 03722, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tae-im","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, College of Medicine, Yonsei University, 50 Yonsei-ro, Seodaemoon-Gu, Seoul 03722, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wan","family":"Namkung","sequence":"additional","affiliation":[{"name":"College of Pharmacy and Yonsei Institute of Pharmaceutical Sciences, Yonsei University, 85 Songdogwahak-ro, Yeonsu-gu, Incheon 21983, Korea"},{"name":"Interdisciplinary Program of Integrated OMICS for Biomedical Science Graduate School, Yonsei University, Seoul 03722, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,4,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1007\/s11882-004-0077-2","article-title":"Dry eye: Diagnosis and current treatment strategies","volume":"4","author":"Collum","year":"2004","journal-title":"Curr. 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