Mechanism of Gastrodin against neurotoxicity based on network pharmacology, molecular docking and experimental verification - 08/11/24
Abstract |
Background |
Disorders of glutamate metabolism and excessive release participat in multiple neuronal pathologies including ischemic stroke (IS), Alzheimer's disease (AD), or Parkinson's disease (PD). Recently, herbal medicines have been widely used and have shown satisfactory results in the treatment of neurological disorders. Gastrodin is a traditional Chinese medicine (TCM) used for the treatment of nerve injuries, spinal cord injuries, and some central nervous system diseases as well. This research examines the neuroprotective effects of Gastrodin against glutamate-induced neurotoxicity in neuronal cells.
Methods |
The HERB database was used to explore the active ingredients and target genes of Gastrodia Elata. The STRING database and Cytoscape software were used to screen and construct the Protein-Protein Interaction (PPI). Furthermore, we used molecular docking to predict the potential targets of Gastrodin. The effects of Gastrodin were revealed by western blot, calcium imaging, membrane clamp, CCK8 and flow cytometry. Neuronal oxidative stress and damage were assessed by measuring malondialdehyde (MDA) levels and superoxide dismutase (SOD) activity. Neuronal morphology was examined using Golgi-Cox staining. Finally, animal behavior was examined using novel object recognition and fear conditioning tests.
Results |
We have obtained 22 components such as TM10, TM17, TM25 (Gastrodin), and 281 targets such as AKT, EGFR, and CDK1 through network pharmacology. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses revealed these genes were significantly enriched in protein phosphorylation, protein serine/threonine/tyrosine kinase activity, apoptosis and HIF-1 signaling pathways, etc. A higher affinity between Gastrodin and AKT was revealed by PPI analysis and molecular docking. Further, Gastrodin significantly inhibited Ca2+ influxes and excitatory synaptic transmission in cortical neurons. In addition, Gastrodin effectively alleviated neuron apoptosis, oxidative stress and damage.
Conclusion |
Gastrodin has neuroprotective effects against glutamate-induced neurotoxicity.
El texto completo de este artículo está disponible en PDF.Graphical Abstract |
Gastrodin, a natural active compound derived from Gastrodia Elata, attenuates glutamate-induced neurotoxicity by inhibiting Ca2+ influx and excitatory synaptic transmission, thereby exerting neuroprotective effects.
Gastrodin, a natural active compound derived from Gastrodia Elata, attenuates glutamate-induced neurotoxicity by inhibiting Ca2+ influx and excitatory synaptic transmission, thereby exerting neuroprotective effects.El texto completo de este artículo está disponible en PDF.
Highlights |
• | Gastrodin, with notably high AKT affinity, was screened by network pharmacology. |
• | Gastrodin inhibits glutamate-induced neuronal calcium overload and neurotoxicity. |
• | Gastrodin provides neuroprotection by reducing neuronal oxidative stress and apoptosis. |
• | Gastrodin promotes neuronal development by reducing synaptic damage and spine loss. |
Abbreviations : AD, AUC, ANOVA, AP, [Ca2+]i, CDM, CFC, CNS, DMEM/F12, Glu, GO, IGluRs, IC50, IS, KEGG, Log FC, LTM, MDA, MEPSC, MF, MS, NMDA, NIH, OFT, ORT, PBS, PDL, PFC, PD, POCD, PPI, SOD, STM, TCM
Keywords : Glutamate, Gastrodin, Network pharmacology, Neurotoxicity, Oxidative stress
Esquema
Vol 180
Artículo 117611- novembre 2024 Regresar al número
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