Rutaecarpine alleviates migraine in nitroglycerin-induced mice by regulating PTEN/PGK1 signaling pathway to activate NRF2 antioxidant system
Background: Due to its widespread prevalence, migraine is a common neurovascular condition that has a major impact on people's health and quality of life. Rutaecarpine (RUT) is one of the main effective components of Evodia rutaecarpa, which has a wide range of biological activities. However, t...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-10-01
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| Series: | Biomedicine & Pharmacotherapy |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0753332223010910 |
| _version_ | 1797686863554674688 |
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| author | Min Xu Zhenhua Shi Ziyang He Xiaoyang Ling Wenhua Wang Hua Liu Mingjie Gong |
| author_facet | Min Xu Zhenhua Shi Ziyang He Xiaoyang Ling Wenhua Wang Hua Liu Mingjie Gong |
| author_sort | Min Xu |
| collection | DOAJ |
| description | Background: Due to its widespread prevalence, migraine is a common neurovascular condition that has a major impact on people's health and quality of life. Rutaecarpine (RUT) is one of the main effective components of Evodia rutaecarpa, which has a wide range of biological activities. However, the exact mechanism by which RUT improves migraine remain unknown. Purpose: The purpose of this study was to investigate whether RUT improves migraine by inhibiting oxidative stress via activating the Nrf2 antioxidant system through the PTEN/PGK1 signaling pathway. Methods: In vivo, a mouse model of chronic migraine (CM) was established by repeated intraperitoneal injection of nitroglycerin (NTG). After treatment with RUT and Sumatriptan, behavioral tests were performed, followed by measurements of oxidative stress-related indicators in the trigeminal nucleus caudalis, expression of proteins associated with the Nrf2 antioxidant system, and the PTEN/PGK1 pathway. In vitro, PC12 cells were stimulated by 100 μM H2O2 for 24 h to induce oxidative stress, which was then treated with RUT. Furthermore, the role of PTEN in antioxidant stress of RUT was elucidated by knockout of the PTEN gene. Results: The results showed that RUT treatment improved NTG-induced migraine in mice by inhibiting oxidative stress. Importantly, RUT inhibited oxidative stress in NTG-induced mice or H2O2-induced PC12 cells via activating the Nrf2 antioxidant system by inhibiting PGK1 activity through PTEN. These results provide evidence that RUT improves migraine by activation of the Nrf2 antioxidant system through the PTEN/PGK1 pathway and provide new insights into the potential use of RUT as an effective drug development candidate for migraine. |
| first_indexed | 2024-03-12T01:11:48Z |
| format | Article |
| id | doaj.art-62e350ff39564075bab4055a81f539ba |
| institution | Directory Open Access Journal |
| issn | 0753-3322 |
| language | English |
| last_indexed | 2024-03-12T01:11:48Z |
| publishDate | 2023-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Biomedicine & Pharmacotherapy |
| spelling | doaj.art-62e350ff39564075bab4055a81f539ba2023-09-14T04:52:34ZengElsevierBiomedicine & Pharmacotherapy0753-33222023-10-01166115300Rutaecarpine alleviates migraine in nitroglycerin-induced mice by regulating PTEN/PGK1 signaling pathway to activate NRF2 antioxidant systemMin Xu0Zhenhua Shi1Ziyang He2Xiaoyang Ling3Wenhua Wang4Hua Liu5Mingjie Gong6Department of Neurosurgery, Kunshan Hospital of Traditional Chinese Medicine, Kunshan Affiliated Hospital of Nanjing University of Chinese Medicine, Kunshan 215300, Jiangsu Province, ChinaDepartment of Neurosurgery, Changshu No.2 People’s Hospital, The Affiliated Changshu Hospital of Nantong University, 215500 Jiangsu Province, ChinaDepartment of Neurosurgery, Kunshan Hospital of Traditional Chinese Medicine, Kunshan Affiliated Hospital of Nanjing University of Chinese Medicine, Kunshan 215300, Jiangsu Province, ChinaDepartment of Neurosurgery, Kunshan Hospital of Traditional Chinese Medicine, Kunshan Affiliated Hospital of Nanjing University of Chinese Medicine, Kunshan 215300, Jiangsu Province, ChinaDepartment of Neurosurgery, Kunshan Hospital of Traditional Chinese Medicine, Kunshan Affiliated Hospital of Nanjing University of Chinese Medicine, Kunshan 215300, Jiangsu Province, ChinaDepartment of Neurosurgery, Affiliated Kunshan Hospital of Jiangsu University, Kunshan 215300, Jiangsu Province, China; Corresponding authors.Department of Neurosurgery, Changshu No.2 People’s Hospital, The Affiliated Changshu Hospital of Nantong University, 215500 Jiangsu Province, China; Corresponding authors.Background: Due to its widespread prevalence, migraine is a common neurovascular condition that has a major impact on people's health and quality of life. Rutaecarpine (RUT) is one of the main effective components of Evodia rutaecarpa, which has a wide range of biological activities. However, the exact mechanism by which RUT improves migraine remain unknown. Purpose: The purpose of this study was to investigate whether RUT improves migraine by inhibiting oxidative stress via activating the Nrf2 antioxidant system through the PTEN/PGK1 signaling pathway. Methods: In vivo, a mouse model of chronic migraine (CM) was established by repeated intraperitoneal injection of nitroglycerin (NTG). After treatment with RUT and Sumatriptan, behavioral tests were performed, followed by measurements of oxidative stress-related indicators in the trigeminal nucleus caudalis, expression of proteins associated with the Nrf2 antioxidant system, and the PTEN/PGK1 pathway. In vitro, PC12 cells were stimulated by 100 μM H2O2 for 24 h to induce oxidative stress, which was then treated with RUT. Furthermore, the role of PTEN in antioxidant stress of RUT was elucidated by knockout of the PTEN gene. Results: The results showed that RUT treatment improved NTG-induced migraine in mice by inhibiting oxidative stress. Importantly, RUT inhibited oxidative stress in NTG-induced mice or H2O2-induced PC12 cells via activating the Nrf2 antioxidant system by inhibiting PGK1 activity through PTEN. These results provide evidence that RUT improves migraine by activation of the Nrf2 antioxidant system through the PTEN/PGK1 pathway and provide new insights into the potential use of RUT as an effective drug development candidate for migraine.http://www.sciencedirect.com/science/article/pii/S0753332223010910MigraineRutaecarpineOxidative stressNrf2PTEN/PGK1 |
| spellingShingle | Min Xu Zhenhua Shi Ziyang He Xiaoyang Ling Wenhua Wang Hua Liu Mingjie Gong Rutaecarpine alleviates migraine in nitroglycerin-induced mice by regulating PTEN/PGK1 signaling pathway to activate NRF2 antioxidant system Biomedicine & Pharmacotherapy Migraine Rutaecarpine Oxidative stress Nrf2 PTEN/PGK1 |
| title | Rutaecarpine alleviates migraine in nitroglycerin-induced mice by regulating PTEN/PGK1 signaling pathway to activate NRF2 antioxidant system |
| title_full | Rutaecarpine alleviates migraine in nitroglycerin-induced mice by regulating PTEN/PGK1 signaling pathway to activate NRF2 antioxidant system |
| title_fullStr | Rutaecarpine alleviates migraine in nitroglycerin-induced mice by regulating PTEN/PGK1 signaling pathway to activate NRF2 antioxidant system |
| title_full_unstemmed | Rutaecarpine alleviates migraine in nitroglycerin-induced mice by regulating PTEN/PGK1 signaling pathway to activate NRF2 antioxidant system |
| title_short | Rutaecarpine alleviates migraine in nitroglycerin-induced mice by regulating PTEN/PGK1 signaling pathway to activate NRF2 antioxidant system |
| title_sort | rutaecarpine alleviates migraine in nitroglycerin induced mice by regulating pten pgk1 signaling pathway to activate nrf2 antioxidant system |
| topic | Migraine Rutaecarpine Oxidative stress Nrf2 PTEN/PGK1 |
| url | http://www.sciencedirect.com/science/article/pii/S0753332223010910 |
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