Polyphyllin VII ameliorates neuroinflammation and brain injury via modulating Treg/Th17 balance in a mouse model of cerebral ischemia-reperfusion injury

•Polyphyllin VII reduced infarct volume, ameliorated brain injury and neuroinflammation, and improved long-term functional recovery of MCAO mice.•Polyphyllin VII increased infiltration of Treg cells and suppressed infiltration of Th1/Th17 cells in ischemic brain.•Polyphyllin VII suppressed mTORC1 ac...

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Vydáno v:	International immunopharmacology Ročník 143; číslo Pt 2; s. 113423
Hlavní autoři:	Sang, Qiuling, Kang, Chunyang, Liu, Dingxi, Wang, Libo, Liu, Xiaoyang, Li, Jia
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	Netherlands Elsevier B.V 25.12.2024
Témata:	Animals Brain - drug effects Brain - metabolism Brain - pathology Brain Injuries - drug therapy Brain Ischemia - drug therapy Brain Ischemia - immunology Cerebral ischemia–reperfusion injury Disease Models, Animal Glycolytic metabolism Humans Infarction, Middle Cerebral Artery - drug therapy Infarction, Middle Cerebral Artery - immunology Male Mice Mice, Inbred C57BL mTORC1 Neuroinflammatory Diseases - drug therapy Neuroinflammatory Diseases - immunology Neuroprotective Agents - pharmacology Neuroprotective Agents - therapeutic use Polyphyllin VII Reperfusion Injury - drug therapy Reperfusion Injury - immunology Saponins - pharmacology Saponins - therapeutic use T-Lymphocytes, Regulatory - drug effects T-Lymphocytes, Regulatory - immunology Th17 Cells - drug effects Th17 Cells - immunology Treg/Th17 polarization Polyphyllin VII Treg/Th17 polarization Cerebral ischemia–reperfusion injury mTORC1 Glycolytic metabolism
ISSN:	1567-5769, 1878-1705, 1878-1705
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Abstract	•Polyphyllin VII reduced infarct volume, ameliorated brain injury and neuroinflammation, and improved long-term functional recovery of MCAO mice.•Polyphyllin VII increased infiltration of Treg cells and suppressed infiltration of Th1/Th17 cells in ischemic brain.•Polyphyllin VII suppressed mTORC1 activation to influence glycolytic metabolism and ROS generation of T cells. Dysregulation of Th17 and Treg cells contributes to the pathophysiology of cerebral ischemia. Metabolic changes of peripheral CD4+ T cells lead to the imbalance of Treg/Th17 polarization, which represents a promising strategy for post-stroke therapy. Polyphyllin VII (PVII), a steroidal saponin extracted from traditional Chinese herb Rhizoma Paridis, has multiple bioactivities, but the potential function of PVII in cerebral ischemia–reperfusion injury is not elucidated yet. In our study, a mouse transient middle cerebral artery occlusion (MCAO) model was constructed. TTC staining, H&E staining, TUNEL staining, ELISA assay, flow cytometry, western blot, RT-qPCR, Open-field test, Morris water maze test, hanging wire test, rotarod test and foot-fault test were performed to evaluate the potential function of PVII in MCAO mice. We found that PVII showed protective effects on cerebral ischemia–reperfusion injury by reducing infarct volume, ameliorating brain injury and neuroinflammation, and improving long-term functional recovery of MCAO mice. PVII promoted Treg infiltration and suppressed infiltration of Th1/Th17 cells in ischemic brain in vivo. Moreover, PVII impaired peripheral CD4+ T cell activation and modulated Treg/Th17 differentiation in vitro. Mechanistically, PVII suppressed mTORC1 activation to influence glycolytic metabolism and ROS generation of T cells, thus leads to the imbalance of Treg/Th17 polarization towards Treg skewed. Furthermore, reactivation of mTORC1 by MHY1485 abolished the influence of PVII on brain injury and neuroinflammation in MCAO mice. Our data provided a novel role of PVII in cerebral ischemia–reperfusion injury via manipulating Treg/Th17 imbalance.
AbstractList	•Polyphyllin VII reduced infarct volume, ameliorated brain injury and neuroinflammation, and improved long-term functional recovery of MCAO mice.•Polyphyllin VII increased infiltration of Treg cells and suppressed infiltration of Th1/Th17 cells in ischemic brain.•Polyphyllin VII suppressed mTORC1 activation to influence glycolytic metabolism and ROS generation of T cells. Dysregulation of Th17 and Treg cells contributes to the pathophysiology of cerebral ischemia. Metabolic changes of peripheral CD4+ T cells lead to the imbalance of Treg/Th17 polarization, which represents a promising strategy for post-stroke therapy. Polyphyllin VII (PVII), a steroidal saponin extracted from traditional Chinese herb Rhizoma Paridis, has multiple bioactivities, but the potential function of PVII in cerebral ischemia–reperfusion injury is not elucidated yet. In our study, a mouse transient middle cerebral artery occlusion (MCAO) model was constructed. TTC staining, H&E staining, TUNEL staining, ELISA assay, flow cytometry, western blot, RT-qPCR, Open-field test, Morris water maze test, hanging wire test, rotarod test and foot-fault test were performed to evaluate the potential function of PVII in MCAO mice. We found that PVII showed protective effects on cerebral ischemia–reperfusion injury by reducing infarct volume, ameliorating brain injury and neuroinflammation, and improving long-term functional recovery of MCAO mice. PVII promoted Treg infiltration and suppressed infiltration of Th1/Th17 cells in ischemic brain in vivo. Moreover, PVII impaired peripheral CD4+ T cell activation and modulated Treg/Th17 differentiation in vitro. Mechanistically, PVII suppressed mTORC1 activation to influence glycolytic metabolism and ROS generation of T cells, thus leads to the imbalance of Treg/Th17 polarization towards Treg skewed. Furthermore, reactivation of mTORC1 by MHY1485 abolished the influence of PVII on brain injury and neuroinflammation in MCAO mice. Our data provided a novel role of PVII in cerebral ischemia–reperfusion injury via manipulating Treg/Th17 imbalance. Dysregulation of Th17 and Treg cells contributes to the pathophysiology of cerebral ischemia. Metabolic changes of peripheral CD4+ T cells lead to the imbalance of Treg/Th17 polarization, which represents a promising strategy for post-stroke therapy. Polyphyllin VII (PVII), a steroidal saponin extracted from traditional Chinese herb Rhizoma Paridis, has multiple bioactivities, but the potential function of PVII in cerebral ischemia-reperfusion injury is not elucidated yet. In our study, a mouse transient middle cerebral artery occlusion (MCAO) model was constructed. TTC staining, H&E staining, TUNEL staining, ELISA assay, flow cytometry, western blot, RT-qPCR, Open-field test, Morris water maze test, hanging wire test, rotarod test and foot-fault test were performed to evaluate the potential function of PVII in MCAO mice. We found that PVII showed protective effects on cerebral ischemia-reperfusion injury by reducing infarct volume, ameliorating brain injury and neuroinflammation, and improving long-term functional recovery of MCAO mice. PVII promoted Treg infiltration and suppressed infiltration of Th1/Th17 cells in ischemic brain in vivo. Moreover, PVII impaired peripheral CD4+ T cell activation and modulated Treg/Th17 differentiation in vitro. Mechanistically, PVII suppressed mTORC1 activation to influence glycolytic metabolism and ROS generation of T cells, thus leads to the imbalance of Treg/Th17 polarization towards Treg skewed. Furthermore, reactivation of mTORC1 by MHY1485 abolished the influence of PVII on brain injury and neuroinflammation in MCAO mice. Our data provided a novel role of PVII in cerebral ischemia-reperfusion injury via manipulating Treg/Th17 imbalance.Dysregulation of Th17 and Treg cells contributes to the pathophysiology of cerebral ischemia. Metabolic changes of peripheral CD4+ T cells lead to the imbalance of Treg/Th17 polarization, which represents a promising strategy for post-stroke therapy. Polyphyllin VII (PVII), a steroidal saponin extracted from traditional Chinese herb Rhizoma Paridis, has multiple bioactivities, but the potential function of PVII in cerebral ischemia-reperfusion injury is not elucidated yet. In our study, a mouse transient middle cerebral artery occlusion (MCAO) model was constructed. TTC staining, H&E staining, TUNEL staining, ELISA assay, flow cytometry, western blot, RT-qPCR, Open-field test, Morris water maze test, hanging wire test, rotarod test and foot-fault test were performed to evaluate the potential function of PVII in MCAO mice. We found that PVII showed protective effects on cerebral ischemia-reperfusion injury by reducing infarct volume, ameliorating brain injury and neuroinflammation, and improving long-term functional recovery of MCAO mice. PVII promoted Treg infiltration and suppressed infiltration of Th1/Th17 cells in ischemic brain in vivo. Moreover, PVII impaired peripheral CD4+ T cell activation and modulated Treg/Th17 differentiation in vitro. Mechanistically, PVII suppressed mTORC1 activation to influence glycolytic metabolism and ROS generation of T cells, thus leads to the imbalance of Treg/Th17 polarization towards Treg skewed. Furthermore, reactivation of mTORC1 by MHY1485 abolished the influence of PVII on brain injury and neuroinflammation in MCAO mice. Our data provided a novel role of PVII in cerebral ischemia-reperfusion injury via manipulating Treg/Th17 imbalance. Dysregulation of Th17 and Treg cells contributes to the pathophysiology of cerebral ischemia. Metabolic changes of peripheral CD4 T cells lead to the imbalance of Treg/Th17 polarization, which represents a promising strategy for post-stroke therapy. Polyphyllin VII (PVII), a steroidal saponin extracted from traditional Chinese herb Rhizoma Paridis, has multiple bioactivities, but the potential function of PVII in cerebral ischemia-reperfusion injury is not elucidated yet. In our study, a mouse transient middle cerebral artery occlusion (MCAO) model was constructed. TTC staining, H&E staining, TUNEL staining, ELISA assay, flow cytometry, western blot, RT-qPCR, Open-field test, Morris water maze test, hanging wire test, rotarod test and foot-fault test were performed to evaluate the potential function of PVII in MCAO mice. We found that PVII showed protective effects on cerebral ischemia-reperfusion injury by reducing infarct volume, ameliorating brain injury and neuroinflammation, and improving long-term functional recovery of MCAO mice. PVII promoted Treg infiltration and suppressed infiltration of Th1/Th17 cells in ischemic brain in vivo. Moreover, PVII impaired peripheral CD4 T cell activation and modulated Treg/Th17 differentiation in vitro. Mechanistically, PVII suppressed mTORC1 activation to influence glycolytic metabolism and ROS generation of T cells, thus leads to the imbalance of Treg/Th17 polarization towards Treg skewed. Furthermore, reactivation of mTORC1 by MHY1485 abolished the influence of PVII on brain injury and neuroinflammation in MCAO mice. Our data provided a novel role of PVII in cerebral ischemia-reperfusion injury via manipulating Treg/Th17 imbalance.
ArticleNumber	113423
Author	Liu, Dingxi Kang, Chunyang Liu, Xiaoyang Wang, Libo Li, Jia Sang, Qiuling
Author_xml	– sequence: 1 givenname: Qiuling surname: Sang fullname: Sang, Qiuling organization: Department of Neuroelectrophysiology, China-Japan Union Hospital of Jilin University, Changchun 130000, China – sequence: 2 givenname: Chunyang surname: Kang fullname: Kang, Chunyang organization: Department of Neurology, China-Japan Union Hospital of Jilin University, Changchun 130000, China – sequence: 3 givenname: Dingxi surname: Liu fullname: Liu, Dingxi organization: Department of Clinical Medicine, Zunyi Medical University, Zhuhai 519041, China – sequence: 4 givenname: Libo surname: Wang fullname: Wang, Libo organization: Department of Neurology, China-Japan Union Hospital of Jilin University, Changchun 130000, China – sequence: 5 givenname: Xiaoyang surname: Liu fullname: Liu, Xiaoyang email: liuxy48@jlu.edu.cn organization: Department of Neurology, China-Japan Union Hospital of Jilin University, Changchun 130000, China – sequence: 6 givenname: Jia orcidid: 0000-0002-3422-2125 surname: Li fullname: Li, Jia email: lijia33233@jlu.edu.cn organization: Department of Neurology, China-Japan Union Hospital of Jilin University, Changchun 130000, China
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Keywords	Polyphyllin VII Treg/Th17 polarization Cerebral ischemia–reperfusion injury mTORC1 Glycolytic metabolism
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Snippet	•Polyphyllin VII reduced infarct volume, ameliorated brain injury and neuroinflammation, and improved long-term functional recovery of MCAO mice.•Polyphyllin... Dysregulation of Th17 and Treg cells contributes to the pathophysiology of cerebral ischemia. Metabolic changes of peripheral CD4 T cells lead to the imbalance... Dysregulation of Th17 and Treg cells contributes to the pathophysiology of cerebral ischemia. Metabolic changes of peripheral CD4+ T cells lead to the...
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SubjectTerms	Animals Brain - drug effects Brain - metabolism Brain - pathology Brain Injuries - drug therapy Brain Ischemia - drug therapy Brain Ischemia - immunology Cerebral ischemia–reperfusion injury Disease Models, Animal Glycolytic metabolism Humans Infarction, Middle Cerebral Artery - drug therapy Infarction, Middle Cerebral Artery - immunology Male Mice Mice, Inbred C57BL mTORC1 Neuroinflammatory Diseases - drug therapy Neuroinflammatory Diseases - immunology Neuroprotective Agents - pharmacology Neuroprotective Agents - therapeutic use Polyphyllin VII Reperfusion Injury - drug therapy Reperfusion Injury - immunology Saponins - pharmacology Saponins - therapeutic use T-Lymphocytes, Regulatory - drug effects T-Lymphocytes, Regulatory - immunology Th17 Cells - drug effects Th17 Cells - immunology Treg/Th17 polarization
Title	Polyphyllin VII ameliorates neuroinflammation and brain injury via modulating Treg/Th17 balance in a mouse model of cerebral ischemia-reperfusion injury
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