Gentiopicroside Attenuated Dopaminergic Neurodegeneration via Inhibiting Neuroinflammatory Responses and Ferroptosis in Experimental Models of Parkinson's Disease
Corresponding Author
Fangling Sun
Department of Laboratory Animal Center, Xuanwu Hospital of Capital Medical University, Beijing Municipal Geriatric Medical Research Center, Beijing, China
Correspondence:
Fangling Sun ([email protected])
Wen Wang ([email protected])
Search for more papers by this authorYifu Ma
Department of Laboratory Animal Center, Xuanwu Hospital of Capital Medical University, Beijing Municipal Geriatric Medical Research Center, Beijing, China
Search for more papers by this authorDan Li
Department of Neurology, Xuanwu Hospital of Capital Medical University, Beijing, China
Search for more papers by this authorQianqian Yang
Department of Laboratory Animal Center, Xuanwu Hospital of Capital Medical University, Beijing Municipal Geriatric Medical Research Center, Beijing, China
Search for more papers by this authorTingwei Yuan
Department of Laboratory Animal Center, Xuanwu Hospital of Capital Medical University, Beijing Municipal Geriatric Medical Research Center, Beijing, China
Search for more papers by this authorTingting Liu
Department of Laboratory Animal Center, Xuanwu Hospital of Capital Medical University, Beijing Municipal Geriatric Medical Research Center, Beijing, China
Search for more papers by this authorXin Tian
Department of Laboratory Animal Center, Xuanwu Hospital of Capital Medical University, Beijing Municipal Geriatric Medical Research Center, Beijing, China
Search for more papers by this authorZixin Zhu
Department of Laboratory Animal Center, Xuanwu Hospital of Capital Medical University, Beijing Municipal Geriatric Medical Research Center, Beijing, China
Search for more papers by this authorWenrong Zheng
Department of Laboratory Animal Center, Xuanwu Hospital of Capital Medical University, Beijing Municipal Geriatric Medical Research Center, Beijing, China
Search for more papers by this authorYufeng Wang
Department of Laboratory Animal Center, Xuanwu Hospital of Capital Medical University, Beijing Municipal Geriatric Medical Research Center, Beijing, China
Search for more papers by this authorCorresponding Author
Wen Wang
Department of Laboratory Animal Center, Xuanwu Hospital of Capital Medical University, Beijing Municipal Geriatric Medical Research Center, Beijing, China
Correspondence:
Fangling Sun ([email protected])
Wen Wang ([email protected])
Search for more papers by this authorCorresponding Author
Fangling Sun
Department of Laboratory Animal Center, Xuanwu Hospital of Capital Medical University, Beijing Municipal Geriatric Medical Research Center, Beijing, China
Correspondence:
Fangling Sun ([email protected])
Wen Wang ([email protected])
Search for more papers by this authorYifu Ma
Department of Laboratory Animal Center, Xuanwu Hospital of Capital Medical University, Beijing Municipal Geriatric Medical Research Center, Beijing, China
Search for more papers by this authorDan Li
Department of Neurology, Xuanwu Hospital of Capital Medical University, Beijing, China
Search for more papers by this authorQianqian Yang
Department of Laboratory Animal Center, Xuanwu Hospital of Capital Medical University, Beijing Municipal Geriatric Medical Research Center, Beijing, China
Search for more papers by this authorTingwei Yuan
Department of Laboratory Animal Center, Xuanwu Hospital of Capital Medical University, Beijing Municipal Geriatric Medical Research Center, Beijing, China
Search for more papers by this authorTingting Liu
Department of Laboratory Animal Center, Xuanwu Hospital of Capital Medical University, Beijing Municipal Geriatric Medical Research Center, Beijing, China
Search for more papers by this authorXin Tian
Department of Laboratory Animal Center, Xuanwu Hospital of Capital Medical University, Beijing Municipal Geriatric Medical Research Center, Beijing, China
Search for more papers by this authorZixin Zhu
Department of Laboratory Animal Center, Xuanwu Hospital of Capital Medical University, Beijing Municipal Geriatric Medical Research Center, Beijing, China
Search for more papers by this authorWenrong Zheng
Department of Laboratory Animal Center, Xuanwu Hospital of Capital Medical University, Beijing Municipal Geriatric Medical Research Center, Beijing, China
Search for more papers by this authorYufeng Wang
Department of Laboratory Animal Center, Xuanwu Hospital of Capital Medical University, Beijing Municipal Geriatric Medical Research Center, Beijing, China
Search for more papers by this authorCorresponding Author
Wen Wang
Department of Laboratory Animal Center, Xuanwu Hospital of Capital Medical University, Beijing Municipal Geriatric Medical Research Center, Beijing, China
Correspondence:
Fangling Sun ([email protected])
Wen Wang ([email protected])
Search for more papers by this authorFunding: This study was funded by the National Natural Science Foundation of China (82173795) and Beijing Municipal Natural Science Foundation (No. 7242217).
Fangling Sun and Yifu Ma have contributed equally to this work and share first authorship.
BCPT recognizes the potential of Natural Product studies in the identification of new therapies but wishes to emphasize that findings based on uncharacterized mixtures of compounds are preliminary in nature and serve primarily as hypothesis-generating to form the basis for more elaborate investigations.
ABSTRACT
Along with the hallmark of α-synuclein deposition, neuroinflammation and iron accumulation have emerged as essential pathological features for dopaminergic neuron degeneration in PD patients and animal models. Preclinical studies have highlighted gentiopicroside's anti-inflammatory activities in treating arthritis, colitis and pancreatitis, and its neuroprotective effects on neurological diseases such as AD, chronic neuropathic pain and ischemia. However, the effects and mechanisms of gentiopicroside on PD-related conditions remain uncertain. Here, we evaluated the potential benefits of gentiopicroside using a unilateral 6-OHDA rat model and a MPP+-induced cell model. Our findings indicated that gentiopicroside improved motor deficits and restored nigral TH-positive neurons in vivo. Mechanistically, gentiopicroside ameliorated inflammatory responses of 6-OHDA-induced rats, decreased NF-κB and pro-inflammatory cytokines levels and reduced Iba-1-positive microglia in the substantia nigra. Furthermore, gentiopicroside regulated the levels of DMT1 and FPN1, thereby inhibiting iron accumulation in PD rats. In vitro, gentiopicroside preserved the viability of MPP+-treated SH-SY5Y cells and suppressed NF-κB activity and its downstream factors' levels. Meanwhile, gentiopicroside inhibited lipid peroxidation and ROS production, while it upregulated the expression of GPX4 in MPP+-treated cells. And these antiferroptosis effects were also linked to iron transporters regulation. Conclusively, gentiopicroside exhibits neuroprotective effects via alleviating neuroinflammation and iron-dependent ferroptosis, offering promise for PD treatment.
Conflicts of Interest
The authors declare no conflicts of interest.
Open Research
Data Availability Statement
The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.
Supporting Information
| Filename | Description |
|---|---|
| bcpt70036-sup-0001-FIGURES1.tifTIFF image, 2.7 MB |
FIGURE S1. Chemical structure and spatial structure of gentiopicroside. (A) Chemical structure of gentiopicroside mol. wt. 356.32. (B) Spatial structure of gentiopicroside. The red balls represent the oxygen atoms, grey balls represent carbon atoms, and white spheres represent hydrogen atoms. |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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