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.