Multi-omics analysis reveals the neuroprotective effect of extract against Parkinson's disease in mouse.

OBJECTIVE: To assess Atractylodis Rhizoma Alba extract (ARE) neuroprotective function in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mice and related genes. METHODS: Examined mRNA-DNA methylation changes induced by ARE in MPTP-induced Parkinson's disease (PD) model's substantia nigra. RESULTS: ARE mitigated MPTP-induced motor impairment in rotarod and open field tests and preserved tyrosine hydroxylase-positive neuronal cells in substantia nigra and striatum. Genome RNA-Sequencing and Methyl-Sequencing in substantia nigra of vehicle/ARE-treated MPTP-induced PD mice showed 84 differentially expressed genes (DEGs) and 1804 differentially methylated regions (DMRs). Upregulated genes involved zinc ion homeostasis, cilium protein localization, and transcription; downregulated genes linked to ephrin receptor signaling, somitogenesis, and gene expression regulation. Hyper/hypomethylated DMRs post-ARE treatment associated with Wnt signaling, mitochondrial organization, dopamine biosynthesis, and hindbrain development. No significant correlation between DEGs and methylated genes related to PD pathogenesis. CONCLUSION: This research has identified the epigenetic targets of ARE's therapeutic action and gives insight on how ARE protects neurons in Parkinson's disease.