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Open AccessArticle

Ginkgo biloba Extract Protects against Methotrexate-Induced Hepatotoxicity: A Computational and Pharmacological Approach

College of Natural and Health Sciences, Zayed University, Abu Dhabi 00000, UAE
Riphah Institute of Pharmaceutical Sciences, Riphah International University, Islamabad 44000, Pakistan
Department of Biological Sciences, National University of Medical Sciences, Rawalpindi 46000, Pakistan
Department of Pharmacology and Toxicology, Faculty of Pharmacy, University of Tabuk, 71491 Tabuk, Saudi Arabia
Department of Botany, University of Malakand, Khyber Pakhtunkhwa 18800, Pakistan
Department of Pharmacognosy, Faculty of Pharmacy, Federal Urdu University of Arts Science and Technology, Karachi 75300, Pakistan
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Academic Editor: Anna Andolfi
Molecules 2020, 25(11), 2540;
Received: 27 April 2020 / Revised: 21 May 2020 / Accepted: 24 May 2020 / Published: 29 May 2020
(This article belongs to the Special Issue Natural Secondary Metabolites)
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-α)-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-α modulation. View Full-Text
Keywords: Ginkgo biloba; hepatotoxicity; TNF-α; IL-1β; JNK; caspase-3; drug-protein interaction Ginkgo biloba; hepatotoxicity; TNF-α; IL-1β; JNK; caspase-3; drug-protein interaction
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Al Kury, L.T.; Dayyan, F.; Ali Shah, F.; Malik, Z.; Khalil, A.A.K.; Alattar, A.; Alshaman, R.; Ali, A.; Khan, Z. Ginkgo biloba Extract Protects against Methotrexate-Induced Hepatotoxicity: A Computational and Pharmacological Approach. Molecules 2020, 25, 2540.

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