6-Gingerol, a Major Constituent of Zingiber officinale Rhizoma, Exerts Anticonvulsant Activity in the Pentylenetetrazole-Induced Seizure Model in Larval Zebrafish
| Autor: | Jolanta Parada-Turska, Lidia Czernicka, Kinga Gawel, Wirginia Kukula-Koch, Katarzyna M. Targowska-Duda, Camila V. Esguerra, Dorota Nieoczym, Nancy Saana Banono |
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| Rok vydání: | 2021 |
| Předmět: |
QH301-705.5
medicine.medical_treatment Pharmacology Inhibitory postsynaptic potential Catalysis Inorganic Chemistry 03 medical and health sciences 0302 clinical medicine neurotransmitter profiling medicine EEG Biology (General) Zingiber officinale Physical and Theoretical Chemistry Receptor QD1-999 Molecular Biology Zebrafish Spectroscopy seizures 030304 developmental biology 0303 health sciences biology pentylenetetrazole Chemistry Organic Chemistry molecular docking General Medicine Glutamic acid zebrafish biology.organism_classification Computer Science Applications Anticonvulsant biology.protein NMDA receptor GRIN2B anticonvulsant activity isolation 6-gingerol 030217 neurology & neurosurgery |
| Zdroj: | International Journal of Molecular Sciences Volume 22 Issue 14 International Journal of Molecular Sciences, Vol 22, Iss 7745, p 7745 (2021) |
| ISSN: | 1422-0067 |
| DOI: | 10.3390/ijms22147745 |
| Popis: | Zingiber officinale is one of the most frequently used medicinal herbs in Asia. Using rodent seizure models, it was previously shown that Zingiber officinale hydroethanolic extract exerts antiseizure activity, but the active constituents responsible for this effect have not been determined. In this paper, we demonstrated that Zingiber officinale methanolic extract exerts anticonvulsant activity in the pentylenetetrazole (PTZ)-induced hyperlocomotion assay in larval zebrafish. Next, we isolated 6-gingerol (6-GIN) – a major constituent of Zingiber officinale rhizoma. We observed that 6-GIN exerted potent dose-dependent anticonvulsant activity in the PTZ-induced hyperlocomotion seizure assay in zebrafish, which was confirmed electroencephalographically. To obtain further insight into the molecular mechanisms of 6-GIN antiseizure activity, we assessed the concentration of two neurotransmitters in zebrafish, i.e., inhibitory γ-aminobutyric acid (GABA) and excitatory glutamic acid (GLU), and their ratio after exposure to acute PTZ dose. Here, 6-GIN decreased GLU level and reduced the GLU/GABA ratio in PTZ-treated fish compared with only PTZ-bathed fish. This activity was associated with the decrease in grin2b, but not gabra1a, grin1a, gria1a, gria2a, and gria3b expression in PTZ-treated fish. Molecular docking to the human NR2B-containing N-methyl-D-aspartate (NMDA) receptor suggests that 6-GIN might act as an inhibitor and interact with the amino terminal domain, the glutamate-binding site, as well as within the ion channel of the NR2B-containing NMDA receptor. In summary, our study reveals, for the first time, the anticonvulsant activity of 6-GIN. We suggest that this effect might at least be partially mediated by restoring the balance between GABA and GLU in the epileptic brain however, more studies are needed to prove our hypothesis. |
| Databáze: | OpenAIRE |
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