{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T06:21:21Z","timestamp":1789021281758,"version":"build-2803163510"},"reference-count":41,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2020,5,29]],"date-time":"2020-05-29T00:00:00Z","timestamp":1590710400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Start-Up Research Grant Program (SRGP) ministry of Higher Education Commission (HEC) Pakistan","award":["21-1615\/SRGP\/HEC"],"award-info":[{"award-number":["21-1615\/SRGP\/HEC"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Ginkgo biloba extract possess several promising biological activities; currently, it is clinically employed in the management of several diseases. This research work aimed to extrapolate the antioxidant and anti-inflammatory effects of Ginkgo biloba (Gb) in methotrexate (MTX)-induced liver toxicity model. These effects were analyzed using different in vivo experimental approaches and by bioinformatics analysis. Male SD rats were grouped as follows: saline; MTX; Gb (pretreated for seven days with 60, 120, and 180 mg\/kg daily dose before MTX treatment); silymarin (followed by MTX treatment); Gb 180 mg\/kg daily only; and silymarin only. Histopathological results revealed that MTX induced marked hepatic injury, associated with a substantial surge in various hepatic enzymes such as alanine transaminase (ALT), aspartate transaminase (AST), and serum alkaline phosphatase (ALP). Furthermore, MTX caused the triggering of oxidative distress associated with a depressed antioxidant system. All these injury markers contributed to a significant release of apoptotic (caspase-3 and c-Jun N-terminal kinases (JNK)) and tumor necrosis factor (TNF-\u03b1)-like inflammatory mediators. Treatment with Gb counteracts MTX-mediated apoptosis and inflammation dose-dependently along with modulating the innate antioxidative mechanisms such as glutathione (GSH) and glutathione S-transferase (GST). These results were further supplemented by in silico study to analyze drug-receptor interactions (for several Gb constituents and target proteins) stabilized by a low energy value and with a good number of hydrogen bonds. These findings demonstrated that Gb could ameliorate MTX-induced elevated liver reactive oxygen species (ROS) and inflammation, possibly by JNK and TNF-\u03b1 modulation.<\/jats:p>","DOI":"10.3390\/molecules25112540","type":"journal-article","created":{"date-parts":[[2020,6,3]],"date-time":"2020-06-03T04:12:09Z","timestamp":1591157529000},"page":"2540","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":50,"title":["Ginkgo biloba Extract Protects against Methotrexate-Induced Hepatotoxicity: A Computational and Pharmacological Approach"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8338-7655","authenticated-orcid":false,"given":"Lina Tariq","family":"Al Kury","sequence":"first","affiliation":[{"name":"College of Natural and Health Sciences, Zayed University, Abu Dhabi 00000, UAE"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fazli","family":"Dayyan","sequence":"additional","affiliation":[{"name":"Riphah Institute of Pharmaceutical Sciences, Riphah International University, Islamabad 44000, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6565-2008","authenticated-orcid":false,"given":"Fawad","family":"Ali Shah","sequence":"additional","affiliation":[{"name":"Riphah Institute of Pharmaceutical Sciences, Riphah International University, Islamabad 44000, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zulkifal","family":"Malik","sequence":"additional","affiliation":[{"name":"Riphah Institute of Pharmaceutical Sciences, Riphah International University, Islamabad 44000, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1450-5635","authenticated-orcid":false,"given":"Atif Ali Khan","family":"Khalil","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, National University of Medical Sciences, Rawalpindi 46000, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdullah","family":"Alattar","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Faculty of Pharmacy, University of Tabuk, 71491 Tabuk, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reem","family":"Alshaman","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Faculty of Pharmacy, University of Tabuk, 71491 Tabuk, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amjad","family":"Ali","sequence":"additional","affiliation":[{"name":"Department of Botany, University of Malakand, Khyber Pakhtunkhwa 18800, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zahid","family":"Khan","sequence":"additional","affiliation":[{"name":"Department of Pharmacognosy, Faculty of Pharmacy, Federal Urdu University of Arts Science and Technology, Karachi 75300, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,5,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"8082","DOI":"10.3748\/wjg.v20.i25.8082","article-title":"Oxidative stress as a crucial factor in liver diseases","volume":"20","author":"Michalak","year":"2014","journal-title":"World J. 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