{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T04:56:12Z","timestamp":1773032172819,"version":"3.50.1"},"reference-count":95,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2023,2,23]],"date-time":"2023-02-23T00:00:00Z","timestamp":1677110400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>NK-4 plays a key role in the treatment of various diseases, such as in hay fever to expect anti-allergic effects, in bacterial infections and gum abscesses to expect anti-inflammatory effects, in scratches, cuts, and mouth sores from bites inside the mouth for enhanced wound healing, in herpes simplex virus (HSV)-1 infections for antiviral effects, and in peripheral nerve disease that causes tingling pain and numbness in hands and feet, while NK-4 is used also to expect antioxidative and neuroprotective effects. We review all therapeutic directions for the cyanine dye NK-4, as well as the pharmacological mechanism of NK-4 in animal models of related diseases. Currently, NK-4, which is sold as an over-the-counter drug in drugstores, is approved for treating allergic diseases, loss of appetite, sleepiness, anemia, peripheral neuropathy, acute suppurative diseases, wounds, heat injuries, frostbite, and tinea pedis in Japan. The therapeutic effects of NK-4\u2019s antioxidative and neuroprotective properties in animal models are now under development, and we hope to apply these pharmacological effects of NK-4 to the treatment of more diseases. All experimental data suggest that different kinds of utility of NK-4 in the treatment of diseases can be developed based on the various pharmacological properties of NK-4. It is expected that NK-4 could be developed in more therapeutic strategies to treat many types of diseases, such as neurodegenerative and retinal degenerative diseases.<\/jats:p>","DOI":"10.3390\/ijms24054411","type":"journal-article","created":{"date-parts":[[2023,2,23]],"date-time":"2023-02-23T03:56:58Z","timestamp":1677124618000},"page":"4411","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Revisiting Cryptocyanine Dye, NK-4, as an Old and New Drug: Review and Future Perspectives"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4406-4183","authenticated-orcid":false,"given":"Shihui","family":"Liu","sequence":"first","affiliation":[{"name":"Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University, Okayama 700-8558, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6570-0030","authenticated-orcid":false,"given":"Toshihiko","family":"Matsuo","sequence":"additional","affiliation":[{"name":"Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University, Okayama 700-8558, Japan"},{"name":"Department of Ophthalmology, Okayama University Hospital, Okayama 700-8558, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1729-1097","authenticated-orcid":false,"given":"Takumi","family":"Abe","sequence":"additional","affiliation":[{"name":"Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama 700-8530, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1254\/fpj.89.1","article-title":"Immunopharmacological actions of lumin (I): Anti-allergic actions of lumin","volume":"89","author":"Sasaki","year":"1987","journal-title":"Nihon Yakurigaku Zasshi"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"14042","DOI":"10.18632\/oncotarget.24449","article-title":"Novel inhibitor candidates of TRPV2 prevent damage of dystrophic myocytes and ameliorate against dilated cardiomyopathy in a hamster model","volume":"9","author":"Iwata","year":"2018","journal-title":"Oncotarget"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/S0300-483X(00)00400-5","article-title":"Gell and Coombs\u2019s classification: Is it still valid?","volume":"15","author":"Descotes","year":"2001","journal-title":"Toxicology"},{"key":"ref_4","first-page":"985","article-title":"Treatment of Allergic Rhinitis","volume":"92","author":"Sur","year":"2015","journal-title":"Am. 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