{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T14:50:59Z","timestamp":1784731859283,"version":"3.55.0"},"reference-count":48,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2013,6,30]],"date-time":"2013-06-30T00:00:00Z","timestamp":1372550400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Hepatology Research"],"published-print":{"date-parts":[[2014,4]]},"abstract":"<jats:sec><jats:title>Aim<\/jats:title><jats:p>Liver fibrosis is a common pathway leading to cirrhosis. Cilostazol, a clinically available oral phosphodiesterase\u20103 inhibitor, has been shown to have antifibrotic potential in experimental non\u2010alcoholic fatty liver disease. However, the detailed mechanisms of the antifibrotic effect and its efficacy in a different experimental model remain elusive.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Male C57BL\/6J mice were assigned to five groups: mice fed a normal diet (groups 1 and 2); 0.1% or 0.3% cilostazol\u2010containing diet (groups 3 and 4, respectively); and 0.125% clopidogrel\u2010containing diet (group 5). Two weeks after feeding, groups 2\u20135 were intraperitoneally administered carbon tetrachloride (<jats:styled-content style=\"fixed-case\">CCl<\/jats:styled-content><jats:sub>4<\/jats:sub>) twice a week for 6 weeks, while group 1 was treated with the vehicle alone. To investigate the effects of cilostazol on hepatic cells, <jats:italic>in vitro<\/jats:italic> studies were conducted using primary hepatic stellate cells (<jats:styled-content style=\"fixed-case\">HSC<\/jats:styled-content>), Kupffer cells and hepatocytes with cilostazol supplementation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Sirius red staining revealed that groups 3 and 4 exhibited a lesser fibrotic area (2.49\u2009\u00b1\u20090.43% and 2.31\u2009\u00b1\u20090.30%, respectively) than group 2 (3.17\u2009\u00b1\u20090.67%, <jats:italic>P<\/jats:italic>\u2009&lt;\u20090.05 and <jats:italic>P<\/jats:italic>\u2009&lt;\u20090.001, respectively). <jats:italic>In vitro<\/jats:italic> studies showed cilostazol dose\u2010dependently suppressed HSC activation (assessed by morphological change, cell proliferation, and the expression of <jats:styled-content style=\"fixed-case\">HSC<\/jats:styled-content> activation markers), suggesting the therapeutic effect of cilostazol is mediated by its direct action on <jats:styled-content style=\"fixed-case\">HSC<\/jats:styled-content>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Cilostazol could alleviate <jats:styled-content style=\"fixed-case\">CCl<\/jats:styled-content><jats:sub>4<\/jats:sub>\u2010induced hepatic fibrogenesis <jats:italic>in vivo<\/jats:italic>, presumably due, at least partly, to its direct effect to suppress <jats:styled-content style=\"fixed-case\">HSC<\/jats:styled-content> activation. Given its clinical availability and safety, it may be a novel therapeutic intervention for chronic liver diseases.<\/jats:p><\/jats:sec>","DOI":"10.1111\/hepr.12140","type":"journal-article","created":{"date-parts":[[2013,4,19]],"date-time":"2013-04-19T08:20:40Z","timestamp":1366359640000},"page":"460-473","source":"Crossref","is-referenced-by-count":21,"title":["Cilostazol attenuates hepatic stellate cell activation and protects mice against carbon tetrachloride\u2010induced liver fibrosis"],"prefix":"10.1111","volume":"44","author":[{"given":"Shunichi","family":"Saito","sequence":"first","affiliation":[{"name":"Department of Surgery Division of Hepato\u2010Pancreato\u2010Biliary Surgery and Transplantation Graduate School of Medicine Kyoto University  Kyoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koichiro","family":"Hata","sequence":"additional","affiliation":[{"name":"Department of Surgery Division of Hepato\u2010Pancreato\u2010Biliary Surgery and 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