Journal Article

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

Malik, Zulkifal, Al Kury, Lina Tariq, Alshaman, Reem, Khan, Zahid, Ali, Amjad, Khalil, Atif Ali Khan, Alattar, Abdullah, Ali Shah, Fawad, Dayyan, Fazli

2020

Overview

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.

• Publisher: MDPI,MDPI AG
• Subject: 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