{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T11:06:16Z","timestamp":1783940776470,"version":"3.55.0"},"reference-count":22,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T00:00:00Z","timestamp":1783900800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Yunnan Provincial Undergraduate Universities\u2019 Association","award":["202301BA070001-048"],"award-info":[{"award-number":["202301BA070001-048"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["CIMB"],"abstract":"<jats:p>Hepatic fibrosis is characterized by excessive extracellular matrix deposition and progressive impairment of liver structure and function. Ellagic acid (EA) has been reported to have antioxidant and anti-inflammatory properties, but its role in hepatic fibrosis remains incompletely understood. A CCl4-induced mouse model of hepatic fibrosis was established. EA was administered by oral gavage at 30, 60, or 120 mg\/kg; colchicine was used as a positive control. Histopathological changes and collagen deposition were assessed using hematoxylin and eosin and Sirius Red staining, respectively. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), interleukin-6 (IL-6), and interleukin-10 (IL-10) concentrations, as well as hepatic malondialdehyde (MDA) and hydroxyproline (Hyp) contents and total superoxide dismutase (T-SOD) activity, were determined. Immunohistochemistry and Western blotting were used to assess fibrosis-associated, EMT-associated, and PI3K\/AKT-related proteins. Network pharmacology analysis was performed to identify candidate targets and pathways. EA treatment ameliorated histopathological injury and collagen deposition in CCl4-treated mice. EA, particularly at the high dose, reduced serum ALT and AST activities and hepatic MDA and Hyp contents while increasing hepatic T-SOD activity. EA treatment was also associated with lower serum IL-6 and higher IL-10 concentrations. In the EA-H group, \u03b1-SMA and collagen I (COL1A1) immunoreactivity were reduced; the abundance of N-cadherin, PI3K, and AKT was lower; and E-cadherin expression was higher. Network pharmacology identified PI3K\/AKT-related signaling as a candidate pathway associated with the anti-fibrotic effects of EA. EA attenuated CCl4-induced hepatic fibrosis and was associated with lower oxidative stress, inflammation, and HSC activation. Direct PI3K\/AKT inhibition was not established.<\/jats:p>","DOI":"10.3390\/cimb48070711","type":"journal-article","created":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T09:51:09Z","timestamp":1783936269000},"page":"711","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Ellagic Acid Attenuates CCl4-Induced Hepatic Fibrosis and Is Associated with Changes in PI3K\/AKT- and EMT-Related Protein Expression"],"prefix":"10.3390","volume":"48","author":[{"given":"Di","family":"Tan","sequence":"first","affiliation":[{"name":"Yunnan Key Laboratory of Insect Biomedical R&D, School of Pharmacy, Dali University, Dali 671000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengyi","family":"Qiao","sequence":"additional","affiliation":[{"name":"Yunnan Key Laboratory of Insect Biomedical R&D, School of Pharmacy, Dali University, Dali 671000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingqing","family":"Zhang","sequence":"additional","affiliation":[{"name":"Yunnan Key Laboratory of Insect Biomedical R&D, School of Pharmacy, Dali University, Dali 671000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chuan","family":"Wang","sequence":"additional","affiliation":[{"name":"Yunnan Key Laboratory of Insect Biomedical R&D, School of Pharmacy, Dali University, Dali 671000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xue","family":"Bai","sequence":"additional","affiliation":[{"name":"Yunnan Key Laboratory of Insect Biomedical R&D, School of Pharmacy, Dali University, Dali 671000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang","family":"Peng","sequence":"additional","affiliation":[{"name":"Yunnan Key Laboratory of Insect Biomedical R&D, School of Pharmacy, Dali University, Dali 671000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8707-8991","authenticated-orcid":false,"given":"Dingyu","family":"Wu","sequence":"additional","affiliation":[{"name":"Yunnan Key Laboratory of Insect Biomedical R&D, School of Pharmacy, Dali University, Dali 671000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Akk\u0131z, H., Gieseler, R.K., and Canbay, A. 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