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Male SD rats (6 weeks old) underwent BDL followed by 15 days of orall administration of EFAX (12.5, 25 or 50\u2009mg\/kg) or ursodeoxycholic acid (25\u2009mg\/kg). BDL caused animal death, ascites formation, alterations in serum biochemistries and severe hepatic injury with excessive collagen deposition, whereas EFAX treatment significantly attenuated these effects. BDL markedly increased the pro-fibrogenic cytokines (TGF-\u03b2, PDGF-\u03b2 and CTGF) and the extracellular matrix indicators \u03b1-SMA, TIMP-1 and collagen type 1 in hepatic proteins and gene expression levels, which were notably normalized by EFAX treatment. EFAX also markedly normalized pro-fibrogenic signaling molecules including Smad2\/3, Smad7, Akt, p44\/42 and p38. We further explored EFAX mechanisms of actions using LX-2 cells (human derived hepatic stellate cell line). Pre-treatment with EFAX drastically attenuated the activation of \u03b1-SMA and Smad2\/3, which are downstream molecules of TGF-\u03b2. These findings suggest that EFAX may be a potent anti-hepatofibrotic agent and its corresponding mechanisms primarily involve the modulation of pro-fibrogenic cytokines.<\/jats:p>","DOI":"10.1038\/srep14531","type":"journal-article","created":{"date-parts":[[2015,9,28]],"date-time":"2015-09-28T09:20:46Z","timestamp":1443432046000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Ethyl acetate fraction of Amomum xanthioides improves bile duct ligation-induced liver fibrosis of rat model via modulation of pro-fibrogenic cytokines"],"prefix":"10.1038","volume":"5","author":[{"given":"Hyeong-Geug","family":"Kim","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jong-Min","family":"Han","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jin-Seok","family":"Lee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jong","family":"Suk Lee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chang-Gue","family":"Son","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2015,9,28]]},"reference":[{"key":"BFsrep14531_CR1","doi-asserted-by":"publisher","first-page":"1887","DOI":"10.1172\/JCI66028","volume":"123","author":"D Schuppan","year":"2013","unstructured":"Schuppan, D. & Kim, Y. 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