{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,25]],"date-time":"2026-10-25T11:41:12Z","timestamp":1792928472797,"version":"4.5.0"},"reference-count":44,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2023,5,30]],"date-time":"2023-05-30T00:00:00Z","timestamp":1685404800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2020R1A2C1004816"],"award-info":[{"award-number":["2020R1A2C1004816"]}],"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":["2021R1A2C2003277"],"award-info":[{"award-number":["2021R1A2C2003277"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Phytotherapy Research"],"published-print":{"date-parts":[[2023,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Though Honokiol was known to have anti\u2010inflammatory, antioxidant, anticancer, antithrombotic, anti\u2010viral, metabolic, antithrombotic, and neurotrophic activities, the underlying mechanisms of Honokiol on epithelial\u2013mesenchymal transition (EMT) mediated liver fibrosis still remain elusive so far. Anti\u2010EMT and antifibrotic effects of Honokiol were explored in murine AML\u201012 hepatocyte cells by 3\u2010(4,5\u2010dimethylthiazol\u20102\u2010yl)\u20102,5\u2010diphenyl\u20102H\u2010tetrazolium bromide (MTT) assay, wound healing assay, Western blotting and also in CCl4\u2010induced liver injury mouse model by immunohistochemistry. Honokiol significantly suppressed transforming growth factor \u03b21 (TGF\u2010\u03b21)\u2010induced EMT and migration of AML\u201012 cells along with decreased EMT phenotypes such as loss of cell adhesion and formation of fibroblast like mesenchymal cells in TGF\u2010\u03b21\u2010treated AML\u201012 cells. Consistently, Honokiol suppressed the expression of Snail and transmembrane protease serine 4 (TMPRSS4), but not p\u2010Smad3, and activated E\u2010cadherin in TGF\u2010\u03b21\u2010treated AML\u201012 cells. Additionally, Honokiol reduced the expression of \u03b2\u2010catenin, p\u2010AKT, p\u2010ERK, p\u2010p38 and increased phosphorylation of glycogen synthase kinase 3 beta (GSK3\u03b2) and JNK in TGF\u2010\u03b21\u2010treated AML\u201012 cells via TGF\u2010\u03b21\/nonSmad pathway. Conversely, GSK3\u03b2 inhibitor SB216763 reversed the ability of Honokiol to reduce Snail, \u03b2\u2010catenin and migration and activate E\u2010cadherin in TGF\u2010\u03b21\u2010treated AML\u201012 cells. Also, Honokiol suppressed hepatic steatosis and necrosis by reducing the expression of TGF\u2010\u03b21 and \u03b1\u2010SMA in liver tissues of CCl4 treated mice. These findings provide scientific evidence that Honokiol suppresses EMT and hepatic fibrosis via activation of E\u2010cadherin\/GSK3\u03b2\/JNK and inhibition of AKT\/ERK\/p38\/\u03b2\u2010catenin\/TMPRSS4 signaling axis.<\/jats:p>","DOI":"10.1002\/ptr.7871","type":"journal-article","created":{"date-parts":[[2023,5,30]],"date-time":"2023-05-30T22:39:22Z","timestamp":1685486362000},"page":"4092-4101","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Honokiol inhibits epithelial\u2013mesenchymal transition and hepatic fibrosis via activation of Ecadherin\/<scp>GSK3\u03b2<\/scp>\/<scp>JNK<\/scp> and inhibition of <scp>AKT<\/scp>\/<scp>ERK<\/scp>\/p38\/\u03b2\u2010catenin\/<scp>TMPRSS4<\/scp> signaling axis"],"prefix":"10.1002","volume":"37","author":[{"given":"Jae Hwa","family":"Seo","sequence":"first","affiliation":[{"name":"College of Korean Medicine Kyung Hee University  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyo\u2010Jung","family":"Lee","sequence":"additional","affiliation":[{"name":"College of Korean Medicine Kyung Hee University  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deok Yong","family":"Sim","sequence":"additional","affiliation":[{"name":"College of Korean Medicine Kyung Hee University  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji Eon","family":"Park","sequence":"additional","affiliation":[{"name":"College of Korean Medicine Kyung Hee University  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chi\u2010Hoon","family":"Ahn","sequence":"additional","affiliation":[{"name":"College of Korean Medicine Kyung Hee University  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Su\u2010Yeon","family":"Park","sequence":"additional","affiliation":[{"name":"College of Korean Medicine Kyung Hee University  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ah\u2010Reum","family":"Cho","sequence":"additional","affiliation":[{"name":"College of Korean Medicine Kyung Hee University  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinsuk","family":"Koo","sequence":"additional","affiliation":[{"name":"Division of Horticulture &amp; Medicinal Plant Andong National University  Andong Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bum Sang","family":"Shim","sequence":"additional","affiliation":[{"name":"College of Korean Medicine Kyung Hee University  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bonglee","family":"Kim","sequence":"additional","affiliation":[{"name":"College of Korean Medicine Kyung Hee University  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2423-1973","authenticated-orcid":false,"given":"Sung\u2010Hoon","family":"Kim","sequence":"additional","affiliation":[{"name":"College of Korean Medicine Kyung Hee University  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,5,30]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.joc.5b01772"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.5754\/hge11750"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/ptr.1757"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.24254"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.2011.01242.x"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1478-3231.2010.02205.x"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jchromb.2014.01.047"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2019.117096"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.3390\/v7092852"},{"issue":"3","key":"e_1_2_9_11_1","first-page":"673","article-title":"Anticancer activity of Honokiol against lymphoid malignant cells via activation of ROS\u2010JNK and attenuation of Nrf2 and NF\u2010kappaB","volume":"21","author":"Gao D. 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