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

• Published in: Molecules (Basel, Switzerland) Switzerland), 2020-05, Vol.25 (11), p.2540
• Main Authors: Al Kury, Lina Tariq, Dayyan, Fazli, Ali Shah, Fawad, Malik, Zulkifal, Khalil, Atif Ali Khan, Alattar, Abdullah, Alshaman, Reem, Ali, Amjad, Khan, Zahid
• Format: Article
• Language: English
• Subjects: Animals; Apoptosis; Biomarkers - metabolism; Caspase 3 - metabolism; caspase-3; Chemical and Drug Induced Liver Injury - drug therapy; Computational Biology; Dose-Response Relationship, Drug; Fatty Acids - chemistry; Ginkgo biloba; hepatotoxicity; Hydrogen Bonding; IL-1β; Immunohistochemistry; Inflammation; JNK; Liver - drug effects; Liver - metabolism; Male; MAP Kinase Kinase 4 - metabolism; Methotrexate - toxicity; Oxidative Stress; Oxygen - metabolism; Plant Extracts - pharmacology; Protective Agents - pharmacology; Protein Binding; Rats; Rats, Sprague-Dawley; Reactive Oxygen Species - metabolism; TNF-α; Tumor Necrosis Factor-alpha - metabolism
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules25112540

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 (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