Logo Medical Science Monitor

Call: +1.631.470.9640
Mon - Fri 10:00 am - 02:00 pm EST

Contact Us

Logo Medical Science Monitor Logo Medical Science Monitor Logo Medical Science Monitor

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 LiuABDEF

DOI: 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

Add Comment 0 Comments

Editorial

01 July 2024 : Editorial  

Editorial: The Global Threats of Increasing Antimicrobial Resistance Require New Approaches to Drug Development, Including Molecular Antimicrobial Adjuvants

Dinah V. Parums

DOI: 10.12659/MSM.945583

Med Sci Monit 2024; 30:e945583

0:00

In Press

Database Analysis  

Local Government Initiatives: A Comprehensive Analysis of Infertility Diagnostic and Treatment Programs in ...

Med Sci Monit In Press; DOI: 10.12659/MSM.943976  

0:00

Clinical Research  

Gender-Specific Risk Factors for Asymmetric Bone Density in Adult Degenerative Lumbar Scoliosis: A Retrospe...

Med Sci Monit In Press; DOI: 10.12659/MSM.944137  

Review article  

Innovative Approaches to Enhance and Measure Medication Adherence in Chronic Disease Management: A Review

Med Sci Monit In Press; DOI: 10.12659/MSM.944605  

Clinical Research  

Effects of Ozone Disc Nucleolysis in Management of Herniated Lumbar Intervertebral Disc: A Retrospective Si...

Med Sci Monit In Press; DOI: 10.12659/MSM.944645  

Most Viewed Current Articles

17 Jan 2024 : Review article   3,694,697

Vaccination Guidelines for Pregnant Women: Addressing COVID-19 and the Omicron Variant

DOI :10.12659/MSM.942799

Med Sci Monit 2024; 30:e942799

0:00

14 Dec 2022 : Clinical Research   1,585,228

Prevalence and Variability of Allergen-Specific Immunoglobulin E in Patients with Elevated Tryptase Levels

DOI :10.12659/MSM.937990

Med Sci Monit 2022; 28:e937990

0:00

16 May 2023 : Clinical Research   690,866

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

0:00

01 Jan 2022 : Editorial   50,699

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

0:00

Your Privacy

We use cookies to ensure the functionality of our website, to personalize content and advertising, to provide social media features, and to analyze our traffic. If you allow us to do so, we also inform our social media, advertising and analysis partners about your use of our website, You can decise for yourself which categories you you want to deny or allow. Please note that based on your settings not all functionalities of the site are available. View our privacy policy.

Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750