Optimized Preparation of Gastrodiae elata Extract Enhances Antiepileptic Effects by Regulating Neuroinflammation,...

Epilepsy is a common chronic neurological disorder characterized by recurrent seizures. Gastrodia elata, the dried tuber of G. elata Bl. (Orchidaceae), is a valuable medicinal and edible botanical resource. This study optimized the preparation of Yellow Rice Wine-Processed G. elata (YPGE) and investigated its antiepileptic effects and underlying mechanisms in a pentylenetetrazol (PTZ)-kindled rat model. Processing parameters were optimized using single-factor experiments combined with an analytic hierarchy process (AHP)-entropy weight method (EWM) weighting strategy and Box-Behnken design-response surface methodology. The optimal parameters were determined as 18% alcohol by volume, 72 °C drying temperature, and 32 h drying time. Compared with unprocessed G. elata (GE), YPGE exhibited 0.54-, 0.13-, 1.87-, and 3.58-fold increases in the contents of gastrodin (GAS), G. elata polysaccharides (GEPs), p-hydroxybenzyl alcohol (p-HBA), and total parishins (TP), respectively, and demonstrated significantly enhanced in vitro antioxidant activity (IC50 values of 2.604, 2.719, and 4.046 mg/mL for DPPH, ABTS, and hydroxyl radicals). In vivo, both GE and YPGE significantly reduced seizure severity, decreased inflammatory cytokines (TNF-α, IL-1β), alleviated oxidative stress (increased SOD and GSH-Px, decreased MDA), and modulated neurotransmitter balance (reduced Glu, increased GABA) in brain tissues. YPGE also upregulated P-glycoprotein expression and reduced neuronal apoptosis in the hippocampal CA1 region by upregulating Bcl-2 and downregulating Bax. These findings suggest that YPGE exerts multi-target antiepileptic effects through synergistic anti-inflammatory, antioxidant, and anti-apoptotic actions, providing experimental evidence for the development of novel antiepileptic therapies based on processed G. elata.