PUBLICATION
Naturally Occurring HMGB1 Inhibitor, Glycyrrhizin, Modulates Chronic Seizures-Induced Memory Dysfunction in Zebrafish Model
- Authors
- Paudel, Y.N., Khan, S.U., Othman, I., Shaikh, M.F.
- ID
- ZDB-PUB-210901-4
- Date
- 2021
- Source
- ACS Chemical Neuroscience 12(18): 3288-3302 (Journal)
- Registered Authors
- Keywords
- High mobility group box 1, T-maze, adult zebrafish, behavior, cognitive decline, epilepsy, neuroinflammation
- MeSH Terms
-
- Animals
- Glycyrrhizic Acid*/pharmacology
- HMGB1 Protein*/metabolism
- Molecular Docking Simulation
- Seizures/chemically induced
- Seizures/drug therapy
- Signal Transduction
- Zebrafish/metabolism
- PubMed
- 34463468 Full text @ ACS Chem. Neurosci.
Citation
Paudel, Y.N., Khan, S.U., Othman, I., Shaikh, M.F. (2021) Naturally Occurring HMGB1 Inhibitor, Glycyrrhizin, Modulates Chronic Seizures-Induced Memory Dysfunction in Zebrafish Model. ACS Chemical Neuroscience. 12(18):3288-3302.
Abstract
Glycyrrhizin (GL) is a well-known pharmacological inhibitor of high mobility group box 1 (HMGB1) and is abundantly present in the licorice root (Glycyrrhiza radix). HMGB1 protein, a key mediator of neuroinflammation, has been implicated in several neurological disorders, including epilepsy. Epilepsy is a devastating neurological disorder with no effective disease-modifying treatment strategies yet, suggesting a pressing need for exploring novel therapeutic options. In the current investigation, using a second hit pentylenetetrazol (PTZ) induced chronic seizure model in adult zebrafish, regulated mRNA expression of HMGB1 was inhibited by pretreatment with GL (25, 50, and 100 mg/kg, ip). A molecular docking study suggests that GL establishes different binding interactions with the various amino acid chains of HMGB1 and Toll-like receptor-4 (TLR4). Our finding suggests that GL pretreatment reduces/suppresses second hit PTZ induced seizure, as shown by the reduction in the seizure score. GL also regulates the second hit PTZ induced behavioral impairment and rescued second hit PTZ related memory impairment as demonstrated by an increase in the inflection ratio (IR) at the 3 h and 24 h T-maze trial. GL inhibited seizure-induced neuronal activity as demonstrated by reduced C-fos mRNA expression. GL also modulated mRNA expression of BDNF, CREB-1, and NPY. The possible mechanism underlying the anticonvulsive effect of GL could be attributed to its anti-inflammatory activity, as demonstrated by the downregulated mRNA expression level of HMGB1, TLR4, NF-kB, and TNF-α. Overall, our finding suggests that GL exerts an anticonvulsive effect and ameliorates seizure-related memory disruption plausibly through regulating of the HMGB1-TLR4-NF-kB axis.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping