{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T03:24:34Z","timestamp":1782789874660,"version":"3.54.5"},"reference-count":43,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2022,3,3]],"date-time":"2022-03-03T00:00:00Z","timestamp":1646265600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Biochem &amp; Molecular Tox"],"published-print":{"date-parts":[[2022,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Prunetin (PRU) is an O\u2010methylated flavonoid that is present in various natural plants and a primary significant compound found in isoflavone. Liver cancer creates major carcinogenic death despite recently advanced therapies. Hepatocellular carcinoma (HCC) treatment and prognosis are better in people with secure liver function. In the present study, we evaluated the action of PRU on diethylnitrosamine (DEN) alone HCC in a rat model through inflammation\u2010mediated cell proliferative phosphoinositide 3\u2010kinase\/protein kinase B (PI3K\/AKT) pathway analysis. Male Wistar rats were divided\u00a0into four groups of six rats each. Group I, normal rats; Group II, DEN alone; Group III, DEN\u2009+\u2009PRU, and Group IV, PRU\u2010alone. All groups of rats carried out\u00a0hepatic cancer development by hypothesis antioxidant, biochemical, cell proliferative, apoptosis, cytokines protein, and gene expression status profiles. In tumor incidence DEN\u2009+\u2009PRU, 100% delayed the tumor growth disappearance of the lesion,\u00a0 and reversal of normal liver architecture was observed. Liver marker enzymes levels decreased when antioxidant levels (superoxidase dismutase, catalase, glutathione peroxidase, and glutathione reductase) were in Group III. Proinflammatory markers nuclear factor\u2010\u03baB, interleukin (IL)\u20106, IL\u20101\u03b2, and tumor necrosis factor \u03b1, were elevated in the rat's serum in Group III. Cell proliferative markers proliferating cell nuclear antigen and Cyclin\u2010D1 protein expressions were downregulated; in contrast, Bcl\u20102, Bax, caspase\u20103, and caspase\u20109 gene expressions were upregulated and then it followed that protein expression of PI3K\/AKT was\u00a0downregulated in PRU\u2010treated groups. PRU assisted reversal of liver damage, antioxidant enzyme restoration cytokine balance, protein, and gene expression to control levels. Taken together, PRU improves functions of the liver, and as such prevents HCC. PRU can be used together with chemopreventives for HCC.<\/jats:p>","DOI":"10.1002\/jbt.23016","type":"journal-article","created":{"date-parts":[[2022,3,3]],"date-time":"2022-03-03T14:03:09Z","timestamp":1646316189000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Involvement of NF\u2010\u03baB\/PI3K\/AKT signaling pathway in the protective effect of prunetin against a diethylnitrosamine induced hepatocellular carcinogenesis in rats"],"prefix":"10.1002","volume":"36","author":[{"given":"Guanghua","family":"Li","sequence":"first","affiliation":[{"name":"Department of Gastrointestinal Surgery, The Second Hospital, Cheeloo College of Medicine Shandong University Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Qi","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Binzhou People's Hospital Binzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Binzhou People's Hospital Binzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4773-2757","authenticated-orcid":false,"given":"Gendong","family":"Tian","sequence":"additional","affiliation":[{"name":"Department of Hepatobiliary Surgery, The Second Hospital, Cheeloo College of Medicine Shandong University Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,3,3]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1713263"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1177\/1756283X13498540"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.3390\/medicina55090526"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(18)30010-2"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1067\/j.cpradiol.2015.04.004"},{"key":"e_1_2_7_7_1","first-page":"136","volume":"10","author":"AlSalloom A. 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