Related Experiment Video
Updated: Sep 26, 2026
Pentylenetetrazole-Induced Kindling Mouse Model
Published on: June 12, 2018
Ganoderic Acid A Ameliorates Pentylenetetrazol-Induced Epilepsy in Mice via Activating KCNQ2
Yang Yao1,2,3, Zhujun Liu1,3, Xujiao Wang1
1Chongqing Key Laboratory of Development and Utilization of Genuine Medicinal Materials in Three Gorges Reservoir Area, Chongqing, China.
Trial Design:
This study aimed to explore the antiepileptic effect of Ganoderic acid A (GA-A) on pentylenetetrazol (PTZ)-induced epilepsy in mice and clarify its underlying mechanism, focusing on the KCNQ2 channel.
Methods:
C57BL/6 mice and hippocampal-specific KCNQ2 knockout mice were used to establish PTZ-induced acute epilepsy models. GA-A was pretreated for 7 days. Epileptic seizures were evaluated by the Racine score and electroencephalogram (EEG). Neuronal injury was detected by HE and TUNEL staining. Neuroinflammation and oxidative stress were assessed by measuring inflammatory factors and oxidative markers. The target interaction between GA-A and KCNQ2 was verified by protein chip, molecular docking, surface plasmon resonance (SPR), and electrophysiological recording.
Results:
GA-A dose-dependently reduced seizure severity, shortened epileptiform discharge duration, alleviated hippocampal neuronal loss and apoptosis, and inhibited neuroinflammation and oxidative stress in PTZ-treated mice. GA-A directly bound to KCNQ2 and activated KCNQ2/3 channels to generate M current. Hippocampal KCNQ2 knockout weakened the ameliorative effect of GA-A on EEG abnormalities and epilepsy-related anxiety- and depression-like behaviors, but did not affect its anti-inflammatory and antioxidant effects.
Conclusion:
GA-A attenuates PTZ-induced epilepsy in mice via activating the KCNQ2 channel to suppress neuronal hyperexcitability and independently inhibiting neuroinflammation and oxidative stress. GA-A is a promising KCNQ2 activator and lead compound for antiepileptic drug development.
