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Open AccessArticle

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

1
College of Natural and Health Sciences, Zayed University, Abu Dhabi 00000, UAE
2
Riphah Institute of Pharmaceutical Sciences, Riphah International University, Islamabad 44000, Pakistan
3
Department of Biological Sciences, National University of Medical Sciences, Rawalpindi 46000, Pakistan
4
Department of Pharmacology and Toxicology, Faculty of Pharmacy, University of Tabuk, 71491 Tabuk, Saudi Arabia
5
Department of Botany, University of Malakand, Khyber Pakhtunkhwa 18800, Pakistan
6
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; https://doi.org/10.3390/molecules25112540
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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