{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:46:02Z","timestamp":1786977962447,"version":"build-2736575974"},"reference-count":63,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2025,5,8]],"date-time":"2025-05-08T00:00:00Z","timestamp":1746662400000},"content-version":"vor","delay-in-days":7,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Biochem &amp;amp; Molecular Tox"],"published-print":{"date-parts":[[2025,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Methotrexate (MTX) has been widely implemented in managing several malignancies, inflammatory conditions such as rheumatic arthritis, and autoimmune illnesses. Hepatotoxicity is a significant side effect of MTX, characterized by increased oxidative stress (OS) and inflammation. Vinpocetine (Vinpo) is a prescription medication with a favorable safety profile. It exerts anti\u2010inflammatory and oxidant implications that might be novel candidates for protecting against MTX\u2010induced hepatotoxicity. This study investigates the therapeutic impact of Vinpo against MTX\u2010stimulated liver damage via the nuclear factor erythroid 2\u2010related factor 2 (Nrf2)\/heme oxygenase\u20101 (HO\u20101) and nuclear factor kappa\u2010light\u2010chain\u2010enhancer of activated B cells (NF\u2010\u03baB) pathways. Rats are allocated into three groups: (1) the Control (saline); (2) the MTX\u2010control (20\u2009mg\/kg; injected once i.p.), and (3) the Vinpo\u2009+\u2009MTX groups. Vinpo was administered orally for 7 days, during which MTX was given intraperitoneally once at the end of Day 3. The liver functions, OS markers, inflammatory mediators, Nrf2, HO\u20101, NF\u2010\u03baB, and apoptotic signals were estimated. Vinpo lead to enhancement in superoxide dismutase (SOD) enzyme activity, elevation in glutathione (GSH), and a hindrance in malondialdehyde (MDA). It also enhances Nrf2 and HO\u20101, inhibiting NF\u2010\u03baB (p65) expression and apoptotic markers. Moreover, Vinpo therapy, in conjunction with MTX, restores the normal histological structure of hepatic tissues. Our data suggested that Vinpo exerts a preventive effect against MTX\u2010induced toxicity through anti\u2010oxidative, anti\u2010inflammatory, and apoptotic activities, mediated via Nrf2\/HO\u20101\/Nf\u2010\u03baB and caspase\u20103\/Bax\/Bcl\u20102 pathways.<\/jats:p>","DOI":"10.1002\/jbt.70300","type":"journal-article","created":{"date-parts":[[2025,5,8]],"date-time":"2025-05-08T06:58:58Z","timestamp":1746687538000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Vinpocetine Mitigates Methotrexate\u2010Induced Liver Injury in Rats Through Modulating Intercellular Communication"],"prefix":"10.1002","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6980-4726","authenticated-orcid":false,"given":"Gellan Alaa Mohamed","family":"Kamel","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Toxicology, Faculty of Pharmacy (Girls) Al\u2010Azhar University Cairo Egypt"},{"name":"Department of Pharmacology &amp; Toxicology College of Pharmacy, Uruk University Baghdad Iraq"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaimaa","family":"Hussein","sequence":"additional","affiliation":[{"name":"Department of Pharmacology College of Pharmacy, Jouf University Sakaka Aljouf Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,5,8]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.7759\/cureus.34468"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbi.2017.04.009"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20205023"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11356-022-22020-0"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2024.137801"},{"key":"e_1_2_9_7_1","first-page":"543","article-title":"Therapeutic Potential of Virgin Coconut Oil in Mitigating Sodium Benzoate\u2010Model of Male Infertility: Role of Nrf2\/Hmox\u20101\/NF\u2010kB Signaling Pathway","volume":"27","author":"Ajibare A. 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