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

Abstract

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.

• Authors: Lina Tariq Al Kury, Fazli Dayyan, Fawad Ali Shah, Zulkifal Malik, Atif Ali Khan Khalil, Abdullah Alattar, Reem Alshaman, Amjad Ali, Zahid Khan
• Journal: Molecules (Basel, Switzerland) (Molecules) Vol. 25 Issue 11 (May 29 2020) ISSN: 1420-3049 [Electronic] Switzerland
• PMID: 32486047 (Publication Type: Journal Article)

Chemical References

• Biomarkers
• Fatty Acids
• Plant Extracts
• Protective Agents
• Reactive Oxygen Species
• Tumor Necrosis Factor-alpha
• Ginkgo biloba extract
• MAP Kinase Kinase 4
• Casp3 protein, rat
• Caspase 3
• Oxygen
• Methotrexate

Topics

• Animals
• Apoptosis
• Biomarkers (metabolism)
• Caspase 3 (metabolism)
• Chemical and Drug Induced Liver Injury (drug therapy)
• Computational Biology
• Dose-Response Relationship, Drug
• Fatty Acids (chemistry)
• Ginkgo biloba
• Hydrogen Bonding
• Immunohistochemistry
• Inflammation
• Liver (drug effects, metabolism)
• MAP Kinase Kinase 4 (metabolism)
• Male
• Methotrexate (toxicity)
• Oxidative Stress
• Oxygen (metabolism)
• Plant Extracts (pharmacology)
• Protective Agents (pharmacology)
• Protein Binding
• Rats
• Rats, Sprague-Dawley
• Reactive Oxygen Species (metabolism)
• Tumor Necrosis Factor-alpha (metabolism)