111614
论文已发表
注册即可获取德孚的最新动态
IF 收录期刊
- 3.4 Breast Cancer (Dove Med Press)
- 3.2 Clin Epidemiol
- 2.6 Cancer Manag Res
- 2.9 Infect Drug Resist
- 3.7 Clin Interv Aging
- 5.1 Drug Des Dev Ther
- 3.1 Int J Chronic Obstr
- 6.6 Int J Nanomed
- 2.6 Int J Women's Health
- 2.9 Neuropsych Dis Treat
- 2.8 OncoTargets Ther
- 2.0 Patient Prefer Adher
- 2.2 Ther Clin Risk Manag
- 2.5 J Pain Res
- 3.0 Diabet Metab Synd Ob
- 3.2 Psychol Res Behav Ma
- 3.4 Nat Sci Sleep
- 1.8 Pharmgenomics Pers Med
- 2.0 Risk Manag Healthc Policy
- 4.1 J Inflamm Res
- 2.0 Int J Gen Med
- 3.4 J Hepatocell Carcinoma
- 3.0 J Asthma Allergy
- 2.2 Clin Cosmet Investig Dermatol
- 2.4 J Multidiscip Healthc
已发表论文
大黄素缓解 MPTP 诱导神经毒性作用的探索性研究：聚焦于 p53-铁死亡信号通路
Authors Chen Y, Zhao Y, Wang Q, Chen Q, Chen X, Yang K
Received 8 March 2025
Accepted for publication 24 July 2025
Published 1 December 2025 Volume 2025:19 Pages 10645—10660
DOI https://doi.org/10.2147/DDDT.S522381
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 3
Editor who approved publication: Dr Tuo Deng
Yujun Chen,1,2,* Yuhang Zhao,1,2,* Qing Wang,1,2 Qiuchi Chen,3 Xiqun Chen,1,2 Kai Yang1,2
1Department of Integrative Medicine, Huashan Hospital, Fudan University, Shanghai, People’s Republic of China; 2Institute of Integrative Medicine, Fudan University, Shanghai, People’s Republic of China; 3Department of Radiology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, 210029, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Xiqun Chen, Department of Integrative Medicine, Huashan Hospital, Fudan University, Shanghai, People’s Republic of China, Email chen_xiqun@fudan.edu.cn Kai Yang, Department of Integrative Medicine, Huashan Hospital, Fudan University, Shanghai, People’s Republic of China, Email kyang19@fudan.edu.cn
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 blotting, qPCR, immunofluorescence, and flow cytometry.
Results: Enrichment analysis revealed that the shared targets of the PD and EMD gene sets were involved in iron metabolism, with TP53 being the most connected protein in the PPI network. Molecular docking analysis suggested that EMD formed a stable complex with p53 or TfR1. Molecular Dynamics Simulation further confirmed that the interactions between EMD and p53 remained stable over time. In vivo studies demonstrated the beneficial effects of EMD in an MPTP mouse model of PD. This action was achieved by inhibiting p53 expression and mitigating ferroptosis signaling in the substantia nigra (SN). EMD similarly attenuated cell injury and ferroptosis in SH-SY5Y cells by inhibiting p53-ferroptosis signaling. In contrast, pharmacological enhancement of p53 nullified these effects in the MPP+-treated SH-SY5Y cells.
Conclusion: These preliminary results indicate that EMD could exert neuroprotective effects against MPTP-induced toxicity, possibly via modulating p53-ferroptosis signaling.
Keywords: emodin, neurodegeneration, MPTP, Parkinson’s disease, ferroptosis, p53
1Department of Integrative Medicine, Huashan Hospital, Fudan University, Shanghai, People’s Republic of China; 2Institute of Integrative Medicine, Fudan University, Shanghai, People’s Republic of China; 3Department of Radiology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, 210029, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Xiqun Chen, Department of Integrative Medicine, Huashan Hospital, Fudan University, Shanghai, People’s Republic of China, Email chen_xiqun@fudan.edu.cn Kai Yang, Department of Integrative Medicine, Huashan Hospital, Fudan University, Shanghai, People’s Republic of China, Email kyang19@fudan.edu.cn
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 blotting, qPCR, immunofluorescence, and flow cytometry.
Results: Enrichment analysis revealed that the shared targets of the PD and EMD gene sets were involved in iron metabolism, with TP53 being the most connected protein in the PPI network. Molecular docking analysis suggested that EMD formed a stable complex with p53 or TfR1. Molecular Dynamics Simulation further confirmed that the interactions between EMD and p53 remained stable over time. In vivo studies demonstrated the beneficial effects of EMD in an MPTP mouse model of PD. This action was achieved by inhibiting p53 expression and mitigating ferroptosis signaling in the substantia nigra (SN). EMD similarly attenuated cell injury and ferroptosis in SH-SY5Y cells by inhibiting p53-ferroptosis signaling. In contrast, pharmacological enhancement of p53 nullified these effects in the MPP+-treated SH-SY5Y cells.
Conclusion: These preliminary results indicate that EMD could exert neuroprotective effects against MPTP-induced toxicity, possibly via modulating p53-ferroptosis signaling.
Keywords: emodin, neurodegeneration, MPTP, Parkinson’s disease, ferroptosis, p53