Icaritin Provides Neuroprotection in Parkinson’s Disease by Attenuating Neuroinflammation, Oxidative Stress, and Energy Deficiency
Abstract
:1. Introduction
2. Materials and Methods
2.1. Reagents and Drugs
2.2. Animals Care
2.3. MPTP Mouse Model of PD
2.4. Behavioral Assessments
2.4.1. Open Field Test
2.4.2. Rotarod Test
2.4.3. Vertical Grid Test
2.5. Measurement of Serum IL-1β and TNF-α Levels
2.6. Measurement of Serotonin, DA, and the Metabolites in Striatum
2.7. Western Blotting Analysis
2.8. Molecular Docking
2.9. Matrix-Assisted Laser Desorption/Ionisation–Mass Spectrometry Imaging (MALDI-MSI)
2.10. Statistical Analysis
3. Results
3.1. Icaritin Improves Motor Dysfunction and Body Weight in PD Mice
3.2. Icaritin Reduced Dopaminergic Neuronal Damage by Inhibiting NLRP3 Inflammasome Activation
3.3. Icaritin Increases the Level of Antioxidant Molecules and Regulates Glutamate–Glutamine Cycle in the Substantia Nigra, a motor nucleus present in the midbrain
3.4. Icaritin Ameliorates Mitochondrial Function in the Substantia Nigra
3.5. Icaritin Might Interact with Blood–Brain Barrier Related Proteins to Improve PD Mice
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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ID | Molecules | Full Name of Target | Source | PDB ID 1 | Docking Score (kcal/mol) | Binding Free Energy (kcal/mol) |
---|---|---|---|---|---|---|
1 | icaritin | tyrosine hydroxylase | Homo | 2XSN | −7.749 | −156.926 |
2 | icaritin | voltage-dependent anion channel 1 | Mus | 3EMN | −5.8431 | −130.237 |
3 | icaritin | hypoxia-inducible factor-1α | Mus | 4ZPR | −5.3245 | −74.195 |
4 | icaritin | ATP synthase subunit 5 beta | Rat | 1mab | −7.082(ADP site) −10.803(ATP site) | −49.804(ADP site) −344.802(ATP site) |
5 | icaritin | succinate dehydrogenase subunit A | Homo | 6vax | −7.078 | −159.603 |
6 | icaritin | NLR family pyrin domain containing 3 | Homo | 6npy | −8.118 | −134.135 |
7 | icaritin | interleukin-1β | Mus | 2mib | −6.217(site 1 in Table S1) | −65.829(site 1 in Table S1) |
8 | icaritin | tumor necrosis factor-α | Mus | 2tnf | −7.440(site 1 in Table S2) | −52.203(site 1 in Table S2) |
9 | icaritin | 12-lipoxygenase | Homo | 3D3L | −4.83 | −24.365 |
10 | icaritin | 15-lipoxygenase | Homo | 1LOX | −8.67 | −44.408 |
11 | icaritin | occludin | Homo | 1XAW | −6.94 | −20.161 |
12 | icaritin | claudin-5 | Homo | 6OV2 | −6.10 | −32.464 |
13 | icaritin | zonula occludens-1 | Homo | 4OEO | −6.85 | −32.049 |
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Wu, H.; Liu, X.; Gao, Z.-Y.; Lin, M.; Zhao, X.; Sun, Y.; Pu, X.-P. Icaritin Provides Neuroprotection in Parkinson’s Disease by Attenuating Neuroinflammation, Oxidative Stress, and Energy Deficiency. Antioxidants 2021, 10, 529. https://doi.org/10.3390/antiox10040529
Wu H, Liu X, Gao Z-Y, Lin M, Zhao X, Sun Y, Pu X-P. Icaritin Provides Neuroprotection in Parkinson’s Disease by Attenuating Neuroinflammation, Oxidative Stress, and Energy Deficiency. Antioxidants. 2021; 10(4):529. https://doi.org/10.3390/antiox10040529
Chicago/Turabian StyleWu, Hao, Xi Liu, Ze-Yu Gao, Ming Lin, Xin Zhao, Yi Sun, and Xiao-Ping Pu. 2021. "Icaritin Provides Neuroprotection in Parkinson’s Disease by Attenuating Neuroinflammation, Oxidative Stress, and Energy Deficiency" Antioxidants 10, no. 4: 529. https://doi.org/10.3390/antiox10040529
APA StyleWu, H., Liu, X., Gao, Z. -Y., Lin, M., Zhao, X., Sun, Y., & Pu, X. -P. (2021). Icaritin Provides Neuroprotection in Parkinson’s Disease by Attenuating Neuroinflammation, Oxidative Stress, and Energy Deficiency. Antioxidants, 10(4), 529. https://doi.org/10.3390/antiox10040529