17 November 2016 : Animal Research
Garcinol Upregulates GABAA and GAD65 Expression, Modulates BDNF-TrkB Pathway to Reduce Seizures in Pentylenetetrazole (PTZ)-Induced Epilepsy
Fang HaoABCDEF, Li-Hua JiaABCDEF, Xiao-Wan LiBCDF, Ying-Rui ZhangBDF, Xue-Wu LiuABDEFDOI: 10.12659/MSM.897579
Med Sci Monit 2016; 22:4415-4425
Abstract
BACKGROUND: Epilepsy is the most predominant neurological disorder characterized by recurrent seizures. Despite treatment with antiepileptic drugs, epilepsy still is a challenge to treat, due to the associated adverse effects of the drugs. Previous investigations have shown critical roles of BDNF-TrkB signalling and expression of glutamic acid decarboxylase 65 (GAD65) and GABAA in the brain during epilepsy. Thus, drugs that could modulate BDNF-TrkB signal and expression of GAD65 and GABAA could aid in therapy. Recent experimental data have focussed on plant-derived compounds in treatments. Garcinol (camboginol), is a polyisoprenylated benzophenone derived from the fruit of Garcinia indica. We investigated the effects of garcinol in pentylenetetrazole (PTZ)-induced epileptic models.
MATERIAL AND METHODS: Seizure scores were measured in epilepsy kindled mice. Neuronal degeneration and apoptosis were assessed by Nissl staining, TUNEL assay, and Fluoro-Jade B staining. Immunohistochemistry was performed to evaluate cleaved caspase-3 expressions. Expression of BDNF, TrkB, GABAA, GAD65, Bad, Bcl-2, Bcl-xL, and Bax were determined by western blots.
RESULTS: Significantly reduced seizure scores and mortality rates were observed with pretreatment with garcinol. Elevated expression of apoptotic proteins and caspase-3 in kindled mice were effectively downregulated by garcinol. Epileptogenic mice presented increased BDNF and TrkB with considerably decreased GABAA and GAD65 expression. Garcinol significantly enhanced GABAA and GAD65 while it suppressed BDNF and TrkB. Garcinol enhanced the performance of mice in Morris water maze tests.
CONCLUSIONS: Garcinol exerts neuroprotective effects via supressing apoptosis and modulating BDNF-TrkB signalling and GAD65/GABAA expressions and also enhanced cognition and memory of the mice.
Keywords: Anticonvulsants - pharmacology, Brain-Derived Neurotrophic Factor - metabolism, Epilepsy - metabolism, Glutamate Decarboxylase - metabolism, Memory - drug effects, Neuroprotective Agents - metabolism, Pentylenetetrazole, Receptor, trkB - metabolism, Receptors, GABA-A - metabolism, Signal Transduction - physiology, Terpenes - pharmacology, Up-Regulation - drug effects
Editorial
01 April 2024 : Editorial
Editorial: Forty Years of Waiting for Prevention and Cure of HIV Infection – Ongoing Challenges and Hopes for Vaccine Development and Overcoming Antiretroviral Drug ResistanceDOI: 10.12659/MSM.944600
Med Sci Monit 2024; 30:e944600
In Press
06 Mar 2024 : Clinical Research
Prevalence and Variation of Medical Comorbidities in Oral Surgery Patients: A Retrospective Study at Jazan ...Med Sci Monit In Press; DOI: 10.12659/MSM.943884
08 Mar 2024 : Clinical Research
Evaluation of Foot Structure in Preschool Children Based on Body MassMed Sci Monit In Press; DOI: 10.12659/MSM.943765
15 Apr 2024 : Laboratory Research
The Role of Copper-Induced M2 Macrophage Polarization in Protecting Cartilage Matrix in OsteoarthritisMed Sci Monit In Press; DOI: 10.12659/MSM.943738
07 Mar 2024 : Clinical Research
Knowledge of and Attitudes Toward Clinical Trials: A Questionnaire-Based Study of 179 Male Third- and Fourt...Med Sci Monit In Press; DOI: 10.12659/MSM.943468
Most Viewed Current Articles
17 Jan 2024 : Review article
Vaccination Guidelines for Pregnant Women: Addressing COVID-19 and the Omicron VariantDOI :10.12659/MSM.942799
Med Sci Monit 2024; 30:e942799
14 Dec 2022 : Clinical Research
Prevalence and Variability of Allergen-Specific Immunoglobulin E in Patients with Elevated Tryptase LevelsDOI :10.12659/MSM.937990
Med Sci Monit 2022; 28:e937990
16 May 2023 : Clinical Research
Electrophysiological Testing for an Auditory Processing Disorder and Reading Performance in 54 School Stude...DOI :10.12659/MSM.940387
Med Sci Monit 2023; 29:e940387
01 Jan 2022 : Editorial
Editorial: Current Status of Oral Antiviral Drug Treatments for SARS-CoV-2 Infection in Non-Hospitalized Pa...DOI :10.12659/MSM.935952
Med Sci Monit 2022; 28:e935952