Icaritin Provides Neuroprotection in Parkinson’s Disease by Attenuating Neuroinflammation, Oxidative Stress, and Energy Deficiency
Neuroinflammation, oxidative stress, and mitochondrial dysfunction are all important pathogenic mechanisms underlying motor dysfunction and dopaminergic neuronal damage observed in patients with Parkinson’s disease (PD). However, despite extensive efforts, targeting inflammation and oxidative stress...
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| Format: | Article |
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MDPI AG
2021-03-01
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| Series: | Antioxidants |
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| Online Access: | https://www.mdpi.com/2076-3921/10/4/529 |
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| author | Hao Wu Xi Liu Ze-Yu Gao Ming Lin Xin Zhao Yi Sun Xiao-Ping Pu |
| author_facet | Hao Wu Xi Liu Ze-Yu Gao Ming Lin Xin Zhao Yi Sun Xiao-Ping Pu |
| author_sort | Hao Wu |
| collection | DOAJ |
| description | Neuroinflammation, oxidative stress, and mitochondrial dysfunction are all important pathogenic mechanisms underlying motor dysfunction and dopaminergic neuronal damage observed in patients with Parkinson’s disease (PD). However, despite extensive efforts, targeting inflammation and oxidative stress using various approaches has not led to meaningful clinical outcomes, and mitochondrial enhancers have also failed to convincingly achieve disease-modifying effects. We tested our hypothesis that treatment approaches in PD should simultaneously reduce neuroinflammation, oxidative stress, and improve alterations in neuronal energy metabolism using the flavonoid icaritin in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD. Using matrix-assisted laser desorption/ionization–mass spectrometry imaging (MALDI-MSI), coupled with biochemical analyses and behavioral tests, we demonstrate that icaritin improves PD by attenuating the the NOD-like receptor family pyrin domain-containing protein 3 (NLRP3) inflammasome activity and stabilizing mitochondrial function, based on our extensive analyses showing the inhibition of NLRP3 inflammasome, reduction of NLRP3-mediated IL-1β secretion, and improvements in the levels of antioxidant molecules. Our data also indicated that icaritin stabilized the levels of proteins related to mitochondrial function, such as voltage-dependent anion channel (VDAC) and ATP synthase subunit beta (ATP5B), as well as those of molecules related to energy metabolism, such as ATP and ADP, ultimately improving mitochondrial dysfunction. By employing molecular docking, we also discovered that icaritin can interact with NLRP3, VDAC, ATP5B, and several blood–brain barrier (BBB)-related proteins. These data provide insights into the promising therapeutic potential of icaritin in PD. |
| first_indexed | 2024-03-10T12:49:08Z |
| format | Article |
| id | doaj.art-301e1c1ad1854e5982f9aac410cc5e54 |
| institution | Directory Open Access Journal |
| issn | 2076-3921 |
| language | English |
| last_indexed | 2024-03-10T12:49:08Z |
| publishDate | 2021-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antioxidants |
| spelling | doaj.art-301e1c1ad1854e5982f9aac410cc5e542023-11-21T13:12:16ZengMDPI AGAntioxidants2076-39212021-03-0110452910.3390/antiox10040529Icaritin Provides Neuroprotection in Parkinson’s Disease by Attenuating Neuroinflammation, Oxidative Stress, and Energy DeficiencyHao Wu0Xi Liu1Ze-Yu Gao2Ming Lin3Xin Zhao4Yi Sun5Xiao-Ping Pu6National Key Research Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing 100191, ChinaNational Key Research Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing 100191, ChinaNational Key Research Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing 100191, ChinaNational Key Research Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing 100191, ChinaNational Key Research Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing 100191, ChinaNational Key Research Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing 100191, ChinaNational Key Research Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing 100191, ChinaNeuroinflammation, oxidative stress, and mitochondrial dysfunction are all important pathogenic mechanisms underlying motor dysfunction and dopaminergic neuronal damage observed in patients with Parkinson’s disease (PD). However, despite extensive efforts, targeting inflammation and oxidative stress using various approaches has not led to meaningful clinical outcomes, and mitochondrial enhancers have also failed to convincingly achieve disease-modifying effects. We tested our hypothesis that treatment approaches in PD should simultaneously reduce neuroinflammation, oxidative stress, and improve alterations in neuronal energy metabolism using the flavonoid icaritin in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD. Using matrix-assisted laser desorption/ionization–mass spectrometry imaging (MALDI-MSI), coupled with biochemical analyses and behavioral tests, we demonstrate that icaritin improves PD by attenuating the the NOD-like receptor family pyrin domain-containing protein 3 (NLRP3) inflammasome activity and stabilizing mitochondrial function, based on our extensive analyses showing the inhibition of NLRP3 inflammasome, reduction of NLRP3-mediated IL-1β secretion, and improvements in the levels of antioxidant molecules. Our data also indicated that icaritin stabilized the levels of proteins related to mitochondrial function, such as voltage-dependent anion channel (VDAC) and ATP synthase subunit beta (ATP5B), as well as those of molecules related to energy metabolism, such as ATP and ADP, ultimately improving mitochondrial dysfunction. By employing molecular docking, we also discovered that icaritin can interact with NLRP3, VDAC, ATP5B, and several blood–brain barrier (BBB)-related proteins. These data provide insights into the promising therapeutic potential of icaritin in PD.https://www.mdpi.com/2076-3921/10/4/529icaritinParkinson’s disease1-methyl-4-phenyl-1,2,3,6-tetrahydropyridineinflammationoxidative stressmitochondrial disfunction |
| spellingShingle | Hao Wu Xi Liu Ze-Yu Gao Ming Lin Xin Zhao Yi Sun Xiao-Ping Pu Icaritin Provides Neuroprotection in Parkinson’s Disease by Attenuating Neuroinflammation, Oxidative Stress, and Energy Deficiency Antioxidants icaritin Parkinson’s disease 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine inflammation oxidative stress mitochondrial disfunction |
| title | Icaritin Provides Neuroprotection in Parkinson’s Disease by Attenuating Neuroinflammation, Oxidative Stress, and Energy Deficiency |
| title_full | Icaritin Provides Neuroprotection in Parkinson’s Disease by Attenuating Neuroinflammation, Oxidative Stress, and Energy Deficiency |
| title_fullStr | Icaritin Provides Neuroprotection in Parkinson’s Disease by Attenuating Neuroinflammation, Oxidative Stress, and Energy Deficiency |
| title_full_unstemmed | Icaritin Provides Neuroprotection in Parkinson’s Disease by Attenuating Neuroinflammation, Oxidative Stress, and Energy Deficiency |
| title_short | Icaritin Provides Neuroprotection in Parkinson’s Disease by Attenuating Neuroinflammation, Oxidative Stress, and Energy Deficiency |
| title_sort | icaritin provides neuroprotection in parkinson s disease by attenuating neuroinflammation oxidative stress and energy deficiency |
| topic | icaritin Parkinson’s disease 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine inflammation oxidative stress mitochondrial disfunction |
| url | https://www.mdpi.com/2076-3921/10/4/529 |
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