Anticonvulsant effect of Stachydrine on pentylenetetrazole-induced kindling seizure mouse model via Notch and NMDAR signaling pathways.

Ethnopharmacological Relevance: Stachydrine (STA), the principal bioactive alkaloid of Leonurus japonicus (Motherwort/"Yi Mu Cao"), may derive its ethnopharmacological relevance for epilepsy management from the botanical origin-Motherwort's documented traditional use in treating seizures and other neurological cardiovascular diseases.

Aim Of The Study: To validate STA's ethnomedicinal claim an anticonvulsant by mechanistically interrogating its dual modulation of Notch1-driven neuroinflammation and NMDA receptor-mediated excitotoxicity, which are two key hallmarks of chronic epileptogenesis.

Materials And Methods: Male C57BL/6 mice were divided into three groups to evaluate the neuroprotective and an anticonvulsant effects of STA in the PTZ-induced seizure model: Control group, PTZ group, and PTZ + STA group. Behavioral seizure scoring and cognitive tests were integrated with EEG recordings to assess neuronal synchronization. Molecular mechanisms were dissected via hippocampal immunohistochemistry and Western blotting.

Results: Our results showed that daily oral administration of STA for a duration of 25 days significantly reduced seizure scores. EEG recordings indicated that STA treatment resulted in a notable reduction in both total brainwave power and firing amplitude within the groups receiving STA. Furthermore, STA administration provided cognitive protection against kindling-associated deficits, as demonstrated by improved alteration behavior and recognition index in Y-maze and object recognition tests. STA administration reduced neuronal loss and glial cell activation. Additionally, significant downregulation of NMDA receptor subunits, CAMK2, caspase-3, Notch1, and Hes1 expression levels was observed following STA administration.

Conclusion: These findings suggest that STA provides neuroprotection against PTZ-induced epilepsy by modulating the Notch and NMDA receptor pathways, thus addressing neuroinflammation and apoptosis resulting from excitotoxicity.