Exploratory Study on the Role of Emodin in Alleviating MPTP-Induced Neurotoxicity: A Focus on p53-Ferroptosis Signaling

作者：Yujun Chen, Yuhang Zhao, Qing Wang, Qiuchi Chen, Xiqun Chen, Kai Yang · 发表于：Drug Design Development and Therapy · 年份：2025 · DOI：10.2147/dddt.s522381 · 被引用次数：4 · 研究领域：Ferroptosis and cancer prognosis、Mast cells and histamine、Synthesis of Organic Compounds

Background: Parkinson’s disease (PD) is a common neurodegenerative disorder. Emodin (EMD), which is derived from multiple Chinese medicinal herbs, has been reported to possess anti-inflammatory, anti-ferroptosis, and neuroprotective effects. However, the mechanisms underlying the regulation of PD-related ferroptosis remain unclear. Objective: To investigate whether EMD protects dopaminergic neurons in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced models of PD and to elucidate its underlying mechanisms. Methods: Potential EMD targets were predicted using SEA and Swiss databases. The PD targets were identified using the OMIM and GeneCards databases. Overlapping genes were introduced to construct protein-protein interactions (PPI) and perform Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. Molecular docking was used to ascertain the possibility of the binding of EMD to p53 and TfR1. The stability of EMD-p53 complex was validated by using molecular dynamics simulations using the YASARA. To validate these mechanisms, we used an MPTP-induced mouse model to investigate the beneficial effects of EMD. Motor function was assessed using the open field and rotarod tests. Malondialdehyde (MDA) and iron contents in the midbrain were determined. SH-SY5Y cells were subjected with 1-methyl-4-phenyl-pyridinium (MPP + ) or ferroptosis inducer. Ferroptosis signaling, iron metabolism, and mitochondrial superoxide levels were investigated using Western...