Multifaceted targets of cannabidiol in epilepsy: Modulating glutamate signaling and beyond.
Comput Biol Med
; 179: 108898, 2024 Sep.
Article
en En
| MEDLINE
| ID: mdl-39047503
ABSTRACT
Cannabidiol has been reported to interact with broad-spectrum biological targets with pleiotropic pharmacology including epilepsy although a cohesive mechanism is yet to be determined. Even though some studies propose that cannabidiol may manipulate glutamatergic signals, there is insufficient evidence to support cannabidiol direct effect on glutamate signaling, which is important in intervening epilepsy. Therefore, the present study aimed to analyze the epilepsy-related targets for cannabidiol, assess the differentially expressed genes with its treatment, and identify the possible glutamatergic signaling target. In this study, the epileptic protein targets of cannabidiol were identified using the Tanimoto coefficient and similarity index-based targets fishing which were later overlapped with the altered expression, epileptic biomarkers, and genetically altered proteins in epilepsy. The common proteins were then screened for possible glutamatergic signaling targets with differentially expressed genes. Later, molecular docking and simulation were performed using AutoDock Vina and GROMACS to evaluate binding affinity, ligand-protein stability, hydrophilic interaction, protein compactness, etc. Cannabidiol identified 30 different epilepsy-related targets of multiple protein classes including G-protein coupled receptors, enzymes, ion channels, etc. Glutamate receptor 2 was identified to be genetically varied in epilepsy which was targeted by cannabidiol and its expression was increased with its treatment. More importantly, cannabidiol showed a direct binding affinity with Glutamate receptor 2 forming a stable hydrophilic interaction and comparatively lower root mean squared deviation and residual fluctuations, increasing protein compactness with broad conformational changes. Based on the cheminformatic target fishing, evaluation of differentially expressed genes, molecular docking, and simulations, it can be hypothesized that cannabidiol may possess glutamate receptor 2-mediated anti-epileptic activities.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Cannabidiol
/
Transducción de Señal
/
Ácido Glutámico
/
Epilepsia
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Simulación del Acoplamiento Molecular
Límite:
Humans
Idioma:
En
Revista:
Comput Biol Med
Año:
2024
Tipo del documento:
Article
Pais de publicación:
Estados Unidos