Cargando…

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

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Al Kury, Lina Tariq, Dayyan, Fazli, Ali Shah, Fawad, Malik, Zulkifal, Khalil, Atif Ali Khan, Alattar, Abdullah, Alshaman, Reem, Ali, Amjad, Khan, Zahid
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7321289/
https://www.ncbi.nlm.nih.gov/pubmed/32486047
http://dx.doi.org/10.3390/molecules25112540
_version_ 1783551430103138304
author Al Kury, Lina Tariq
Dayyan, Fazli
Ali Shah, Fawad
Malik, Zulkifal
Khalil, Atif Ali Khan
Alattar, Abdullah
Alshaman, Reem
Ali, Amjad
Khan, Zahid
author_facet Al Kury, Lina Tariq
Dayyan, Fazli
Ali Shah, Fawad
Malik, Zulkifal
Khalil, Atif Ali Khan
Alattar, Abdullah
Alshaman, Reem
Ali, Amjad
Khan, Zahid
author_sort Al Kury, Lina Tariq
collection PubMed
description 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.
format Online
Article
Text
id pubmed-7321289
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-73212892020-06-29 Ginkgo biloba Extract Protects against Methotrexate-Induced Hepatotoxicity: A Computational and Pharmacological Approach Al Kury, Lina Tariq Dayyan, Fazli Ali Shah, Fawad Malik, Zulkifal Khalil, Atif Ali Khan Alattar, Abdullah Alshaman, Reem Ali, Amjad Khan, Zahid Molecules Article 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. MDPI 2020-05-29 /pmc/articles/PMC7321289/ /pubmed/32486047 http://dx.doi.org/10.3390/molecules25112540 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Al Kury, Lina Tariq
Dayyan, Fazli
Ali Shah, Fawad
Malik, Zulkifal
Khalil, Atif Ali Khan
Alattar, Abdullah
Alshaman, Reem
Ali, Amjad
Khan, Zahid
Ginkgo biloba Extract Protects against Methotrexate-Induced Hepatotoxicity: A Computational and Pharmacological Approach
title Ginkgo biloba Extract Protects against Methotrexate-Induced Hepatotoxicity: A Computational and Pharmacological Approach
title_full Ginkgo biloba Extract Protects against Methotrexate-Induced Hepatotoxicity: A Computational and Pharmacological Approach
title_fullStr Ginkgo biloba Extract Protects against Methotrexate-Induced Hepatotoxicity: A Computational and Pharmacological Approach
title_full_unstemmed Ginkgo biloba Extract Protects against Methotrexate-Induced Hepatotoxicity: A Computational and Pharmacological Approach
title_short Ginkgo biloba Extract Protects against Methotrexate-Induced Hepatotoxicity: A Computational and Pharmacological Approach
title_sort ginkgo biloba extract protects against methotrexate-induced hepatotoxicity: a computational and pharmacological approach
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7321289/
https://www.ncbi.nlm.nih.gov/pubmed/32486047
http://dx.doi.org/10.3390/molecules25112540
work_keys_str_mv AT alkurylinatariq ginkgobilobaextractprotectsagainstmethotrexateinducedhepatotoxicityacomputationalandpharmacologicalapproach
AT dayyanfazli ginkgobilobaextractprotectsagainstmethotrexateinducedhepatotoxicityacomputationalandpharmacologicalapproach
AT alishahfawad ginkgobilobaextractprotectsagainstmethotrexateinducedhepatotoxicityacomputationalandpharmacologicalapproach
AT malikzulkifal ginkgobilobaextractprotectsagainstmethotrexateinducedhepatotoxicityacomputationalandpharmacologicalapproach
AT khalilatifalikhan ginkgobilobaextractprotectsagainstmethotrexateinducedhepatotoxicityacomputationalandpharmacologicalapproach
AT alattarabdullah ginkgobilobaextractprotectsagainstmethotrexateinducedhepatotoxicityacomputationalandpharmacologicalapproach
AT alshamanreem ginkgobilobaextractprotectsagainstmethotrexateinducedhepatotoxicityacomputationalandpharmacologicalapproach
AT aliamjad ginkgobilobaextractprotectsagainstmethotrexateinducedhepatotoxicityacomputationalandpharmacologicalapproach
AT khanzahid ginkgobilobaextractprotectsagainstmethotrexateinducedhepatotoxicityacomputationalandpharmacologicalapproach