{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T05:40:14Z","timestamp":1768282814273,"version":"3.49.0"},"reference-count":35,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2018,1,11]],"date-time":"2018-01-11T00:00:00Z","timestamp":1515628800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Chem Biol Drug Des"],"published-print":{"date-parts":[[2018,4]]},"abstract":"<jats:p>Liver fibrosis is a major health concern worldwide. Inhibitors of Signal Transducer and Activator of Transcription 3 (<jats:styled-content style=\"fixed-case\">STAT<\/jats:styled-content>3) have been reported to attenuate experimental liver fibrosis. Therefore, the aim of this study was to investigate the potential ameliorative effect of cucurbitacin\u2010B (Cucu\u2010B) against <jats:styled-content style=\"fixed-case\">CC<\/jats:styled-content>l<jats:sub>4<\/jats:sub>\u2010induced liver fibrosis in mice. Treatment with Cucu\u2010B (5\u00a0mg\/kg) preserved hepatocellular membrane integrity and amended the metabolic function as indicated by preventing the rise of serum liver function markers. This was confirmed histologically. <jats:styled-content style=\"fixed-case\">CC<\/jats:styled-content>l<jats:sub>4<\/jats:sub>\u2010induced oxidative stress was improved by Cucu\u2010B treatment (1 and 5\u00a0mg\/kg). Furthermore, Cucu\u2010B treatment ameliorated the fibrotic state as evidenced by inhibiting the rise of hydroxyproline liver content and mitigating the overexpressions of collagen\u20101\u03b1, \u03b1\u2010smooth muscle actin (\u03b1\u2010<jats:styled-content style=\"fixed-case\">SMA<\/jats:styled-content>) and transforming growth factor beta (<jats:styled-content style=\"fixed-case\">TGF<\/jats:styled-content>\u2010\u03b2) as well as the downexpression of matrix metalloproteinase\u20102 (<jats:styled-content style=\"fixed-case\">MMP<\/jats:styled-content>\u20102) <jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content>. Importantly, <jats:styled-content style=\"fixed-case\">STAT<\/jats:styled-content>3 activity was inhibited by Cucu\u2010B as confirmed by decreased phosphorylation of <jats:styled-content style=\"fixed-case\">STAT<\/jats:styled-content>3 without changing total <jats:styled-content style=\"fixed-case\">STAT<\/jats:styled-content>3 expression. This was substantiated by the reduced Bcl\u20102 together with increased Bax <jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content> expressions with subsequent elevation of Bax\/Bcl\u20102 ratio. In conclusion, Cucu\u2010B hampers <jats:styled-content style=\"fixed-case\">CC<\/jats:styled-content>l<jats:sub>4<\/jats:sub>\u2010induced liver fibrosis in mice. This can be attributed\u2014at least partly\u2014to inhibition of oxidative stress, inflammation and <jats:styled-content style=\"fixed-case\">STAT<\/jats:styled-content>3 signalling.<\/jats:p>","DOI":"10.1111\/cbdd.13160","type":"journal-article","created":{"date-parts":[[2017,12,18]],"date-time":"2017-12-18T02:06:39Z","timestamp":1513562799000},"page":"933-941","source":"Crossref","is-referenced-by-count":37,"title":["Cucurbitacin\u2010B attenuates <scp>CC<\/scp>l<sub>4<\/sub>\u2010induced hepatic fibrosis in mice through inhibition of <scp>STAT<\/scp>\u20103"],"prefix":"10.1111","volume":"91","author":[{"given":"Alaliaa M.","family":"Sallam","sequence":"first","affiliation":[{"name":"Department of Biochemistry Faculty of Pharmacy Ain Shams University  Abbasia, Cairo Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ahmed","family":"Esmat","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology Faculty of Pharmacy Ain Shams University  Abbasia, Cairo Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0400-9075","authenticated-orcid":false,"given":"Ashraf B.","family":"Abdel\u2010Naim","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology Faculty of Pharmacy Ain Shams University  Abbasia, Cairo Egypt"},{"name":"Department of Pharmacology and Toxicology Faculty of Pharmacy King Abdulaziz University  Jeddah Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2018,1,11]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-230X-10-40"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2008.03.003"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1586\/egh.11.92"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI24282"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.4103\/0973-1296.96553"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1097\/CAD.0b013e3283541384"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2007.09.075"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.3109\/08923973.2015.1085065"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmc.2012.03.001"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.3892\/mmr.2014.2581"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1158\/1940-6207.CAPR-14-0286"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0117794"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.12659\/MSM.900523"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.apjtm.2015.06.012"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.277.5332.1630"},{"key":"e_1_2_7_17_1","first-page":"93","volume-title":"Cancer Princ. 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