{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T23:02:55Z","timestamp":1792623775702,"version":"4.5.0"},"reference-count":36,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2021,12,12]],"date-time":"2021-12-12T00:00:00Z","timestamp":1639267200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000646","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["19K07377"],"award-info":[{"award-number":["19K07377"]}],"id":[{"id":"10.13039\/501100000646","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP19fk0210059"],"award-info":[{"award-number":["JP19fk0210059"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP18fk0210027"],"award-info":[{"award-number":["JP18fk0210027"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP19fk0210040"],"award-info":[{"award-number":["JP19fk0210040"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP18fk0210040"],"award-info":[{"award-number":["JP18fk0210040"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Chronic liver injury may result in hepatic fibrosis, which can progress to cirrhosis and eventually liver failure. There are no drugs that are specifically approved for treating hepatic fibrosis. The natural product honokiol (HNK), a bioactive compound extracted from Magnolia grandiflora, represents a potential tool in the management of hepatic fibrosis. Though HNK has been reported to exhibit suppressive effects in a rat fibrosis model, the mechanisms accounting for this suppression remain unclear. In the present study, the anti-fibrotic effects of HNK on the liver were evaluated in vivo and in vitro. In vivo studies utilized a murine liver fibrosis model, in which fibrosis is induced by treatment with carbon tetrachloride (CCl4). For in vitro studies, LX-2 human hepatic stellate cells (HSCs) were treated with HNK, and expression of markers of fibrosis, cell viability, the transforming growth factor-\u03b2 (TGF-\u03b21)\/SMAD signaling pathway, and autophagy were analyzed. HNK was well tolerated and significantly attenuated CCl4-induced liver fibrosis in vivo. Moreover, HNK decreased HSC activation and collagen expression by downregulating the TGF-\u03b21\/SMAD signaling pathway and autophagy. These results suggest that HNK is a new potential candidate for the treatment of hepatic fibrosis through suppressing both TGF-\u03b21\/SMAD signaling and autophagy in HSCs.<\/jats:p>","DOI":"10.3390\/ijms222413354","type":"journal-article","created":{"date-parts":[[2021,12,13]],"date-time":"2021-12-13T01:28:11Z","timestamp":1639358891000},"page":"13354","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Honokiol Acts as a Potent Anti-Fibrotic Agent in the Liver through Inhibition of TGF-\u03b21\/SMAD Signaling and Autophagy in Hepatic Stellate Cells"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9347-5766","authenticated-orcid":false,"given":"Seita","family":"Kataoka","sequence":"first","affiliation":[{"name":"Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kamigyo-ku, Kyoto 602-8566, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atsushi","family":"Umemura","sequence":"additional","affiliation":[{"name":"Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kamigyo-ku, Kyoto 602-8566, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keiichiro","family":"Okuda","sequence":"additional","affiliation":[{"name":"Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kamigyo-ku, Kyoto 602-8566, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1033-2642","authenticated-orcid":false,"given":"Hiroyoshi","family":"Taketani","sequence":"additional","affiliation":[{"name":"Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kamigyo-ku, Kyoto 602-8566, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3658-5894","authenticated-orcid":false,"given":"Yuya","family":"Seko","sequence":"additional","affiliation":[{"name":"Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kamigyo-ku, Kyoto 602-8566, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taichiro","family":"Nishikawa","sequence":"additional","affiliation":[{"name":"Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kamigyo-ku, Kyoto 602-8566, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kanji","family":"Yamaguchi","sequence":"additional","affiliation":[{"name":"Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kamigyo-ku, Kyoto 602-8566, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michihisa","family":"Moriguchi","sequence":"additional","affiliation":[{"name":"Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kamigyo-ku, Kyoto 602-8566, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshihiro","family":"Kanbara","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Saiseikai Suita Hospital, Suita 564-0013, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6798-6383","authenticated-orcid":false,"given":"Jack L.","family":"Arbiser","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Emory University School of Medicine, Atlanta, GA 30322, USA"},{"name":"Veterans Affairs Medical Center, Decatur, GA 30322, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4120-9121","authenticated-orcid":false,"given":"Toshihide","family":"Shima","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Saiseikai Suita Hospital, Suita 564-0013, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2390-3400","authenticated-orcid":false,"given":"Takeshi","family":"Okanoue","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Saiseikai Suita Hospital, Suita 564-0013, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9890-3635","authenticated-orcid":false,"given":"Yoshito","family":"Itoh","sequence":"additional","affiliation":[{"name":"Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kamigyo-ku, Kyoto 602-8566, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,12,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Mokdad, A., Lopez, A.D., Shahraz, S., Lozano, R., Stanaway, J., Murray, C.J.L., and Naghavi, M. 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