Panax notoginseng Flower Extract Attenuates Pentylenetetrazole Induced Epilepsy by Restoring Glutamate Homeostasis

摘要

Objective: The study aimed to investigate the neuroprotective and antiepileptic effects of Panax notoginseng Flower Extract(PNF) in a chronic pentylenetetrazole(PTZ)-kindled mouse model and to explore its potential mechanisms, with a focus on glutamate homeostasis. Methods: A chronic epilepsy model was established in ICR mice via repeated intraperitoneal injections of subconvulsive doses of PTZ. After successful kindling, the mice were orally administered PNF(1.5 g/kg or 3 g/kg) for 30 days. Seizure severity was assessed using Racine's scale. We further evaluated neuronal survival, systemic and cerebral cytokine levels, hippocampal glutamate concentrations(measured via in vivo microdialysis coupled with LC-MS/MS analysis), and the expression of key glutamate homeostasis-related proteins, including GLT-1, GLAST, and glutamine synthetase(GS). Results: PNF treatment significantly reduced seizure severity and preserved NeuN+ neurons in the cortex and hippocampal CA1 region of PTZ kindled mice. Furthermore, PNF alleviated systemic and neuroinflammation, as evidenced by reduced levels of IL-1β, IL-6, and TNF-α, alongside an increase in IL-10, in both the serum and brain homogenates. PNF reduced hippocampal glutamate accumulation and upregulated GLT-1, GLAST, and GS expression, which were altered by PTZ stimulation. Conclusion: PNF extract exhibits significant neuroprotective and antiepileptic effects in PTZ-kindled mice. These benefits are likely mediated through the restoration of glutamate homeostasis and suppression of inflammatory responses. Our findings support the therapeutic potential of PNF as a complementary agent for the management of epilepsy, warranting further clinical development.

关键词

epilepsy / Panax notoginseng flower(PNF) / neuroprotection / glutamate / neuroinflammation

基金资助

The Chinese Medicine Featured Education and Science Cooperation Project (90011662620002); the grant International Cooperation Project of Prevention and Treatment of Major Diseases with Chinese Medicine (0610-2240NF021548); the High end Experts Support Program from the Ministry of Science and Technology (DL 2021110001L and H20240747)