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.