标题：Garcinol Upregulates GABA(A) and GAD65 Expression, Modulates BDNF-TrkB Pathway to Reduce Seizures in Pentylenetetrazole (PTZ)-Induced Epilepsy
作者：Hao, Fang; Jia, Li-Hua; Li, Xiao-Wan; Zhang, Ying-Rui; Liu, Xue-Wu
作者机构：[Hao, Fang; Liu, Xue-Wu] Shandong Univ, Qilu Hosp, Dept Neurol, Jinan, Shandong, Peoples R China.; [Hao, Fang; Jia, Li-Hua; Li, Xiao-Wan; Zhang, Yin 更多
通讯作者地址：[Liu, XW]Shandong Univ, Qilu Hosp, Dept Neurol, Jinan, Shandong, Peoples R China.
来源：MEDICAL SCIENCE MONITOR
关键词：Garcinia Cambogia; Pentylenetetrazole; Receptor, trkB; Receptors, GABA
摘要：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 GABA A in the brain during epilepsy. Thus, drugs that could modulate BDNF-TrkB signal and expression of GAD65 and GABA A 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/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, GABA A, 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 GABA A and GAD65 expression. Garcinol significantly enhanced GABA A 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/GABA A expressions and also enhanced cognition and memory of the mice.