Parthenolide alleviates cognitive dysfunction and neurotoxicity via regulation of AMPK/GSK3β(Ser9)/Nrf2 signaling pathway
Alzheimer's disease (AD) stands as the predominant age-related neurodegenerative disorder, for which efficacious treatment remains elusive. An auspicious avenue for this disease lies in natural compounds sourced from tranditional medicine and plant origins. Parthenolide (PTN) is a natural produ...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-12-01
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| Series: | Biomedicine & Pharmacotherapy |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0753332223017079 |
| _version_ | 1797404599955488768 |
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| author | Jinfeng Sun Liwei Li Li Xiong Fan Chen Lingyu She Hao Tang Yuqing Zeng Ying Duan Luyao Li Wei Wang Gao Li Xia Zhao Guang Liang |
| author_facet | Jinfeng Sun Liwei Li Li Xiong Fan Chen Lingyu She Hao Tang Yuqing Zeng Ying Duan Luyao Li Wei Wang Gao Li Xia Zhao Guang Liang |
| author_sort | Jinfeng Sun |
| collection | DOAJ |
| description | Alzheimer's disease (AD) stands as the predominant age-related neurodegenerative disorder, for which efficacious treatment remains elusive. An auspicious avenue for this disease lies in natural compounds sourced from tranditional medicine and plant origins. Parthenolide (PTN) is a natural product with multiple biological functionsand. Recent investigations have illuminated PTN's protective properties against neurological maladies; however, its potential therapeutic role against AD remains uncharted. This study aims to explore the role of PTN in treating AD. Our in vitro findings underscore PTN's bioactivity, as evidenced by its capacity to curtail apoptosis, reduce reactive oxygen species (ROS) production, and restore mitochondrial membrane potential in PC12 cells. Moreover, PTN treatment demonstrates a capacity to ameliorate deficits in spatial learning and memory in the 3 ×Tg-AD murine model. Notably, PTN's therapeutic efficacy surpasses that of a clinical agent, donepezil. Mechanistically, PTN's neuroprotective effects stem from its adept regulation of the AMPK/GSK3β(ser9)/Nrf2 signaling pathway and protection on neuronal cells from ROS-related apoptosis. Although the molecular target and the pre-clinical evaluations of PTN need to be further explored, this study indicates PTN as a potential agent or lead compound for the drug development against AD. |
| first_indexed | 2024-03-09T02:57:22Z |
| format | Article |
| id | doaj.art-b8f2c5b8e1b04eda91ba7460265a2144 |
| institution | Directory Open Access Journal |
| issn | 0753-3322 |
| language | English |
| last_indexed | 2024-03-09T02:57:22Z |
| publishDate | 2023-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Biomedicine & Pharmacotherapy |
| spelling | doaj.art-b8f2c5b8e1b04eda91ba7460265a21442023-12-05T04:14:46ZengElsevierBiomedicine & Pharmacotherapy0753-33222023-12-01169115909Parthenolide alleviates cognitive dysfunction and neurotoxicity via regulation of AMPK/GSK3β(Ser9)/Nrf2 signaling pathwayJinfeng Sun0Liwei Li1Li Xiong2Fan Chen3Lingyu She4Hao Tang5Yuqing Zeng6Ying Duan7Luyao Li8Wei Wang9Gao Li10Xia Zhao11Guang Liang12Department of Pharmacy and Institute of Inflammation, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, Zhejiang 310014, China; Zhejiang TCM Key Laboratory of Pharmacology and Translational Research of Natural Products, School of Pharmaceutical Sciences, Hangzhou Medical College, Hangzhou, Zhejiang 310014, China; Key Laboratory of Natural Medicines of the Changbai Mountain, Ministry of Education, College of Pharmacy, Yanbian University, Yanji, Jilin 133002, ChinaZhejiang TCM Key Laboratory of Pharmacology and Translational Research of Natural Products, School of Pharmaceutical Sciences, Hangzhou Medical College, Hangzhou, Zhejiang 310014, ChinaZhejiang TCM Key Laboratory of Pharmacology and Translational Research of Natural Products, School of Pharmaceutical Sciences, Hangzhou Medical College, Hangzhou, Zhejiang 310014, ChinaZhejiang TCM Key Laboratory of Pharmacology and Translational Research of Natural Products, School of Pharmaceutical Sciences, Hangzhou Medical College, Hangzhou, Zhejiang 310014, ChinaZhejiang TCM Key Laboratory of Pharmacology and Translational Research of Natural Products, School of Pharmaceutical Sciences, Hangzhou Medical College, Hangzhou, Zhejiang 310014, ChinaZhejiang TCM Key Laboratory of Pharmacology and Translational Research of Natural Products, School of Pharmaceutical Sciences, Hangzhou Medical College, Hangzhou, Zhejiang 310014, ChinaZhejiang TCM Key Laboratory of Pharmacology and Translational Research of Natural Products, School of Pharmaceutical Sciences, Hangzhou Medical College, Hangzhou, Zhejiang 310014, ChinaKey Laboratory of Natural Medicines of the Changbai Mountain, Ministry of Education, College of Pharmacy, Yanbian University, Yanji, Jilin 133002, ChinaZhejiang TCM Key Laboratory of Pharmacology and Translational Research of Natural Products, School of Pharmaceutical Sciences, Hangzhou Medical College, Hangzhou, Zhejiang 310014, ChinaAffiliated Yongkang First People's Hospital, Hangzhou Medical College, Hangzhou, Zhejiang 310012, ChinaKey Laboratory of Natural Medicines of the Changbai Mountain, Ministry of Education, College of Pharmacy, Yanbian University, Yanji, Jilin 133002, China; Corresponding author.Zhejiang TCM Key Laboratory of Pharmacology and Translational Research of Natural Products, School of Pharmaceutical Sciences, Hangzhou Medical College, Hangzhou, Zhejiang 310014, China; Affiliated Yongkang First People's Hospital, Hangzhou Medical College, Hangzhou, Zhejiang 310012, China; Corresponding authors at: Zhejiang TCM Key Laboratory of Pharmacology and Translational Research of Natural Products, School of Pharmaceutical Sciences, Hangzhou Medical College, Hangzhou, Zhejiang 310014, China.Department of Pharmacy and Institute of Inflammation, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, Zhejiang 310014, China; Zhejiang TCM Key Laboratory of Pharmacology and Translational Research of Natural Products, School of Pharmaceutical Sciences, Hangzhou Medical College, Hangzhou, Zhejiang 310014, China; Corresponding authors at: Zhejiang TCM Key Laboratory of Pharmacology and Translational Research of Natural Products, School of Pharmaceutical Sciences, Hangzhou Medical College, Hangzhou, Zhejiang 310014, China.Alzheimer's disease (AD) stands as the predominant age-related neurodegenerative disorder, for which efficacious treatment remains elusive. An auspicious avenue for this disease lies in natural compounds sourced from tranditional medicine and plant origins. Parthenolide (PTN) is a natural product with multiple biological functionsand. Recent investigations have illuminated PTN's protective properties against neurological maladies; however, its potential therapeutic role against AD remains uncharted. This study aims to explore the role of PTN in treating AD. Our in vitro findings underscore PTN's bioactivity, as evidenced by its capacity to curtail apoptosis, reduce reactive oxygen species (ROS) production, and restore mitochondrial membrane potential in PC12 cells. Moreover, PTN treatment demonstrates a capacity to ameliorate deficits in spatial learning and memory in the 3 ×Tg-AD murine model. Notably, PTN's therapeutic efficacy surpasses that of a clinical agent, donepezil. Mechanistically, PTN's neuroprotective effects stem from its adept regulation of the AMPK/GSK3β(ser9)/Nrf2 signaling pathway and protection on neuronal cells from ROS-related apoptosis. Although the molecular target and the pre-clinical evaluations of PTN need to be further explored, this study indicates PTN as a potential agent or lead compound for the drug development against AD.http://www.sciencedirect.com/science/article/pii/S0753332223017079Alzheimer’s diseaseParthenolideCell apoptosisCognitive deficitsAMPK |
| spellingShingle | Jinfeng Sun Liwei Li Li Xiong Fan Chen Lingyu She Hao Tang Yuqing Zeng Ying Duan Luyao Li Wei Wang Gao Li Xia Zhao Guang Liang Parthenolide alleviates cognitive dysfunction and neurotoxicity via regulation of AMPK/GSK3β(Ser9)/Nrf2 signaling pathway Biomedicine & Pharmacotherapy Alzheimer’s disease Parthenolide Cell apoptosis Cognitive deficits AMPK |
| title | Parthenolide alleviates cognitive dysfunction and neurotoxicity via regulation of AMPK/GSK3β(Ser9)/Nrf2 signaling pathway |
| title_full | Parthenolide alleviates cognitive dysfunction and neurotoxicity via regulation of AMPK/GSK3β(Ser9)/Nrf2 signaling pathway |
| title_fullStr | Parthenolide alleviates cognitive dysfunction and neurotoxicity via regulation of AMPK/GSK3β(Ser9)/Nrf2 signaling pathway |
| title_full_unstemmed | Parthenolide alleviates cognitive dysfunction and neurotoxicity via regulation of AMPK/GSK3β(Ser9)/Nrf2 signaling pathway |
| title_short | Parthenolide alleviates cognitive dysfunction and neurotoxicity via regulation of AMPK/GSK3β(Ser9)/Nrf2 signaling pathway |
| title_sort | parthenolide alleviates cognitive dysfunction and neurotoxicity via regulation of ampk gsk3β ser9 nrf2 signaling pathway |
| topic | Alzheimer’s disease Parthenolide Cell apoptosis Cognitive deficits AMPK |
| url | http://www.sciencedirect.com/science/article/pii/S0753332223017079 |
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