Targeting excitatory/inhibitory neurotransmission by wogonin: integrated In Silico and In Vivo evidence in Parkinson's disease model.

Aim: The present study aimed to investigate neuroprotective potential of wogonin in rotenone-induced PD, with particular focus on modulation of excitatory/inhibitory (E/I) neurotransmission and other pathological factors, including oxidative stress, neuroinflammation, and apoptosis.

Methods: In-silico molecular docking and molecular dynamics simulation (MDS) were employed to assess binding affinity and stability of wogonin. Wistar rats were divided into six groups (n = 8) and treated with vehicle (1% DMSO), rotenone (2 mg/kg), wogonin (5, 10, and 20 mg/kg), and standard treatment for 21 days. Behavioral assessments were conducted weekly. On day 22, brain tissues were collected for analysis. Oxidative stress markers (MDA, GSH, and LDH) and Ca²⁺ levels were measured using chemical assays. IL-6, caspase-3/9, parvalbumin, and c-FOS were quantified by ELISA and dopamine levels by HPLC-ECD. Western blotting was performed for GABA-A, gephyrin, MAO-B, and α-synuclein, while tyrosine hydroxylase (TH) expression and neuronal integrity were evaluated histologically.

Results: Docking and MDS suggested stable drug-target interactions. Rotenone-induced motor deficits, elevated MDA, LDH, IL-6, caspase-3/9, Ca²⁺, and c-FOS level and reduced GSH, dopamine, gephyrin, GABA-A, and TH expression. Wogonin dose-dependently attenuated these changes and preserved striatal histoarchitecture.

Conclusion: Wogonin modulated the markers related to E/I neurotransmission and exhibited neuroprotection, highlighting its multitarget therapeutic potential in PD.