{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T04:52:30Z","timestamp":1771476750360,"version":"3.50.1"},"reference-count":79,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2025,7,4]],"date-time":"2025-07-04T00:00:00Z","timestamp":1751587200000},"content-version":"vor","delay-in-days":3,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T00:00:00Z","timestamp":1751328000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Biochem &amp;amp; Molecular Tox"],"published-print":{"date-parts":[[2025,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Diethylnitrosamine (DEN) is a highly toxic compound with teratogenic, mutagenic, and carcinogenic properties. Embelin, a natural benzoquinone derived from Embelia ribes, has shown potential therapeutic effects. This study evaluated embelin's impact on biochemical, histopathological, and gene expression changes in DEN\u2010induced liver injury. Twenty\u2010eight male Wistar albino rats were assigned to four groups: Sham, Embelin (E), DEN, and DEN\u2009+\u2009E. DEN groups received a single intraperitoneal dose of 200\u2009mg\/kg DEN, while E and DEN\u2009+\u2009E groups were administered 1.2\u2009mg\/kg embelin for 14 days. Liver enzyme levels, lipid profiles, total antioxidant status (TAS), and total oxidant status (TOS) were measured. RT\u2010PCR analysis was performed to assess sonic hedgehog (\n                    <jats:italic>Shh, Ptch1, Smo, Gli1<\/jats:italic>\n                    ), inflammatory (\n                    <jats:italic>TNF\u2010\u03b1, IL\u20106, IL\u20101\u03b2<\/jats:italic>\n                    ) and apoptotic (\n                    <jats:italic>Tp53, casp3, Bcl\u20102, Bax<\/jats:italic>\n                    ) gene expression in liver tissue. Histopathological examination showed that DEN induced fibrosis, congestion, apoptosis, and bile pigment accumulation, which were significantly mitigated by embelin. Embelin decreased liver enzyme and lipid levels, increased the activity of TAS, which is an antioxidant capacity, decreased the gene expression levels of pro\u2010inflammatory cytokines\n                    <jats:italic>TNF\u2010\u03b1, IL\u20106, IL\u20101\u03b2<\/jats:italic>\n                    , and the activation of the Shh signaling pathway. It also increased the expression of\n                    <jats:italic>Bcl\u20102<\/jats:italic>\n                    and decreased the gene expression levels of\n                    <jats:italic>Tp53, Casp3<\/jats:italic>\n                    ,\n                    <jats:italic>Bax<\/jats:italic>\n                    , and inhibited liver apoptosis. These results imply that embelin may have a therapeutic effect on DEN\u2010induced liver damage by preventing degenerative liver problems, regulating liver functions, suppressing oxidative stress, the inflammatory and apoptotic response, and modulating the Shh signaling pathways.\n                  <\/jats:p>","DOI":"10.1002\/jbt.70389","type":"journal-article","created":{"date-parts":[[2025,7,4]],"date-time":"2025-07-04T08:31:59Z","timestamp":1751617919000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Embelin Ameliorates Diethylnitrosamine\u2010Induced Liver Injury Through Down\u2010Regulation of Apoptosis, Oxidative Stress and Inflammation by Influencing the Shh\/Gli1 Signaling Pathways"],"prefix":"10.1002","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-5514-3326","authenticated-orcid":false,"given":"Ayd\u0131n","family":"Akcilar","sequence":"first","affiliation":[{"name":"Faculty of Medicine, Experimental Animal Research Center K\u00fctahya Health Sciences University K\u00fctahya Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2308-0811","authenticated-orcid":false,"given":"Hikmet","family":"Keles","sequence":"additional","affiliation":[{"name":"Department of Pathology Faculty of Veterinary Medicine Afyon Kocatepe University Afyonkarahisar Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4720-1945","authenticated-orcid":false,"given":"Raziye","family":"Akcilar","sequence":"additional","affiliation":[{"name":"Department of Physiology Faculty of Medicine K\u00fctahya Health Sciences University K\u00fctahya Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3819-6822","authenticated-orcid":false,"given":"Fatma Emel","family":"Kocak","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry Faculty of Medicine K\u00fctahya Health Sciences University K\u00fctahya Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,7,4]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-291X(80)90598-7"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1155\/2018\/9472939"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1590\/1519-6984.186565"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/ptr.2883"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.taap.2019.114611"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2021.111335"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.2174\/1389557519666191015202723"},{"key":"e_1_2_11_9_1","first-page":"16","article-title":"Histochemical Localization of Embelin in Fruits of Embellia Ribes Brum and Its Quantification","volume":"1","author":"Ferreria G. 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