LB068 - PROTEOMIC ANALYSIS OF THE NEUROPROTECTIVE EFFECTS OF GASTRODIA ELATA BLUME IN THE SUBSTANTIA NIGRA OF A PARKINSON'S DISEASE MOUSE MODEL

LB068

PROTEOMIC ANALYSIS OF THE NEUROPROTECTIVE EFFECTS OF GASTRODIA ELATA BLUME IN THE SUBSTANTIA NIGRA OF A PARKINSON'S DISEASE MOUSE MODEL

S. Kim^1,*, C.-H. Bae², J. E. Seo¹, W. Xu¹, H.-Y. Kim³

¹Department of Korean Medical Science, Pusan National University, Yangsan, ²Herbal Medicine Resources Research Center, Korean Institute of Oriental Medicine, Naju, ³Reserch Institute for Korean Medicine, Pusan National University, Yangsan, Korea, Republic Of

Rationale: Recent studies suggest that Gastrodia elata Blume (GE) and its active compound gastrodin have neuroprotective effects in Parkinson’s disease (PD) models. This study examined the protective effects of GE on dopaminergic neurons in an 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mouse model and analyzed proteomic changes in the substantia nigra using two-dimensional gel electrophoresis.

Methods: Dried Gastrodia elata rhizomes (100 g) were extracted twice with 70% ethanol using ultrasonication and overnight incubation, followed by filtration, vacuum concentration, and freeze-drying (yield: 5.5%). Male C57BL/6 mice (n = 27) were randomly divided into three groups: Saline, MPTP, and MPTP+GEB. MPTP (30 mg/kg) was administered intraperitoneally once daily for 5 consecutive days, and GEB extract (800 mg/kg) was administered orally for 12 days. Dopaminergic neuron survival in the substantia nigra was evaluated by tyrosine hydroxylase (TH) immunostaining. For proteomic analysis, substantia nigra tissues were collected and lysed in a urea-thiourea buffer. Proteins were separated by two-dimensional gel electrophoresis (2-DE), stained with Coomassie Brilliant Blue, and analyzed using PDQuest software. Differentially expressed protein spots were excised and identified using MALDI-TOF mass spectrometry and MASCOT database searches. Statistical analyses were performed using one-way ANOVA followed by Bonferroni post hoc tests, with statistical significance set at p < 0.05.

Results: TH immunostaining revealed a significant loss of dopaminergic neurons in the MPTP group compared to the Saline group, whereas the MPTP+GEB group showed significantly increased neuron survival compared to the Saline group. Proteomic analysis identified 378 protein spots, among which 11 showed statistically significant expression changes. MALDI-TOF MS analysis revealed altered expression of proteins such as thimet oligopeptidase, T-complex protein 1 subunit alpha, and ubiquitin carboxyl-terminal hydrolase L1, which are involved in the neuroprotective effects of GE by reducing oxidative stress, promoting autophagy, and enhancing ubiquitin-mediated protein degradation, respectively.

Conclusion: These findings suggest that GEB exerts neuroprotective effects against MPTP-induced dopaminergic neuronal loss by reducing oxidative stress, preventing protein misfolding and aggregation, promoting autophagy, and preserving cytoskeletal and synaptic integrity. These multifaceted mechanisms highlight the therapeutic potential of GEB in Parkinson’s disease.

Disclosure of Interest: None declared