Gastrodia elata Blume-Acorus tatarinowii Schott herb pair alleviates seizures and hippocampal injury in TLE rats with alterations in mitophagy and NLRP3 inflammasome pathways.

ETHNOPHARMACOLOGICAL RELEVANCE: Temporal lobe epilepsy (TLE) is the most common drug-resistant focal epilepsy, with its progression tightly linked to mitochondrial dysfunction, neuroinflammation and neuronal injury. The herbal pair Gastrodia elata Blume and Acorus tatarinowii Schott (GEAT) is traditionally used for convulsive disorders, but its anti-epileptic mechanisms remain unclear.

AIM OF THE STUDY: To investigate the therapeutic potential of GEAT in TLE and explore the potential mechanisms associated with its neuroprotective effects.

MATERIALS AND

METHODS

The components of GEAT were characterized by LC-MS/MS. A pilocarpine-induced TLE rat model was used. Seizure severity was scored using the Racine scale. Anxiety-like and memory behaviors were assessed using open-field and fear-conditioning tests. The therapeutic effects and mechanisms of GEAT were evaluated using histology, immunofluorescence, transmission electron microscopy, the JC-1 assay, and Western blotting.

RESULTS

GEAT reduced seizures and improved anxiety-like behavior and contextual memory impairment in TLE rats. GEAT also attenuated hippocampal neuronal injury, reduced glial reactivity and altered microglial phenotype-related markers, and improved mitochondrial ultrastructural abnormalities and membrane potential. Additionally, GEAT treatment was associated with increased expression of PINK1/Parkin-related proteins and lysosome-associated proteins, as well as changes in HMGB1/TLR4/NF-κB/NLRP3 inflammasome-related markers and apoptosis-/pyroptosis-related proteins.

CONCLUSIONS

Our findings show that GEAT alleviates seizures and hippocampal injury in TLE rats, accompanied by changes in mitophagy and lysosome-related proteins and HMGB1/TLR4/NF-κB/NLRP3 inflammasome markers, suggesting potential involvement of these pathways in its protective effects. This study provides evidence for the application of GEAT in TLE and a basis for further exploring the link between mitochondrial quality control and neuroinflammation in TLE.