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It is proven that methotrexate-induced hepatotoxicity occurs even at relatively low doses. It is known that garden cress has anti-inflammatory, antioxidant, and hepatoprotective properties. This study investigates the potential alleviating effect of garden cress oil (GCO) against MTX-induced hepatotoxicity in rats. The chemical composition of GCO was assessed using GC\/MS analysis. Liver damage was studied using hepatotoxicity biomarkers, molecular, and histological analysis. Also, the effects of GCO on TNF-\u03b1 and caspase-3 proteins were evaluated through molecular docking studies. The results demonstrated that MTX caused liver damage, as seen by elevated levels of the liver enzymes ALT, AST, and ALP. Likewise, MTX showed clear signs of apoptosis, such as increased mRNA expression levels of BAX, Caspase-3, and P53, and increased liver inflammation indicated by higher levels of TNF-\u03b1 expression. MTX exhibited significant liver damage, as demonstrated by histological examination. Treatment with GCO effectively alleviated the apoptotic effects of MTX, provided protection against inflammation, and restored histological alterations. GC\/MS metabolite profiling of garden cress oil revealed the presence of several phytoconstituents, including tocopherols, erucic acid, sesamolin, linoleic acid, vaccenic acid, oleic acid, stearic acid, and palmitic acid, that showed strong binding affinities toward TNF-\u03b1 and caspase-3 proteins in molecular docking studies, which could explain the anti-apoptotic and anti-inflammatory potential of GCO.<\/jats:p>","DOI":"10.1038\/s41598-025-89550-8","type":"journal-article","created":{"date-parts":[[2025,2,20]],"date-time":"2025-02-20T06:32:12Z","timestamp":1740033132000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["In vivo and in silico studies on the potential role of garden cress oil in attenuating methotrexate-induced inflammation and apoptosis in liver"],"prefix":"10.1038","volume":"15","author":[{"given":"Dalia M.","family":"Mabrouk","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Radwa H.","family":"El-Akad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed H.","family":"Afifi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hafiza A.","family":"Sharaf","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonia L.","family":"El-Sharkawy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aida I.","family":"El makawy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,2,20]]},"reference":[{"key":"89550_CR1","doi-asserted-by":"publisher","first-page":"115953","DOI":"10.1016\/j.biopha.2023.115953","volume":"170","author":"E Kalantari","year":"2024","unstructured":"Kalantari, E., Zolbanin, N. 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