The combination of Astragalus membranaceus and ligustrazine mitigates cerebral ischemia‐reperfusion injury via regulating NR2B‐ERK/CREB signaling
Abstract Background and purpose Cerebral ischemia‐reperfusion (I/R) injury is a major factor underlying the high mortality and morbidity rates in stroke patients. Our previous study found that the combination of Astragalus membranaceus extract and ligustrazine (Ast+Lig) treatment could protect brain...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2023-02-01
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| Series: | Brain and Behavior |
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| Online Access: | https://doi.org/10.1002/brb3.2867 |
| _version_ | 1811164238531526656 |
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| author | Xialing Tang Shanshan Xie Huajun Wang Yingbin Li Zhiyu Lai Shuangxi Sun Ruanhuan Pan Yan Huang Jun Cai |
| author_facet | Xialing Tang Shanshan Xie Huajun Wang Yingbin Li Zhiyu Lai Shuangxi Sun Ruanhuan Pan Yan Huang Jun Cai |
| author_sort | Xialing Tang |
| collection | DOAJ |
| description | Abstract Background and purpose Cerebral ischemia‐reperfusion (I/R) injury is a major factor underlying the high mortality and morbidity rates in stroke patients. Our previous study found that the combination of Astragalus membranaceus extract and ligustrazine (Ast+Lig) treatment could protect brain tissues against inflammation in rats with thrombolytic cerebral ischemia. Activation of N‐methyl‐D‐aspartate receptors (NMDAR) is implicated in brain damage induced by cerebral I/R injury. Methods We used in vivo and in vitro models of cerebral I/R injury for middle cerebral artery occlusion/reperfusion in mice and oxygen‐glucose deprivation/reoxygenation in primary rat cerebral cortical neurons to evaluate the protective effects of Ast+Lig on cerebral I/R injury, and whether the protective mechanism was related to the regulation of NMDAR‐ERK/CREB signaling. Results Treatment with Ast+Lig, or MK‐801 (an inhibitor of NMDAR) significantly ameliorated neurological deficits, decreased infarct volumes, suppressed neuronal damage and Ca2+ influx, and maintained the mitochondrial membrane potential in vivo and in vitro following cerebral I/R injury based on 2,3,5‐triphenyl tetrazolium chloride staining, immunohistochemistry, and immunofluorescent staining. Furthermore, treatment with Ast+Lig evidently prevented the upregulation of NR2B, but not NR2A, in vivo and in vitro following cerebral I/R injury based on western blotting and reverse transcription‐quantitative PCR analyses. Moreover, treatment with Ast+Lig significantly increased the phosphorylation of ERK and CREB, as well as increasing their mRNA expression levels in vivo and in vitro following cerebral I/R injury. Conclusions The overall results thus suggest that the Ast+Lig combination conferred neuroprotective properties against cerebral I/R injury via regulation of the NR2B‐ERK/CREB signaling pathway. |
| first_indexed | 2024-04-10T15:19:18Z |
| format | Article |
| id | doaj.art-4f5adde0c69e4880887a51996f56979b |
| institution | Directory Open Access Journal |
| issn | 2162-3279 |
| language | English |
| last_indexed | 2024-04-10T15:19:18Z |
| publishDate | 2023-02-01 |
| publisher | Wiley |
| record_format | Article |
| series | Brain and Behavior |
| spelling | doaj.art-4f5adde0c69e4880887a51996f56979b2023-02-14T16:52:41ZengWileyBrain and Behavior2162-32792023-02-01132n/an/a10.1002/brb3.2867The combination of Astragalus membranaceus and ligustrazine mitigates cerebral ischemia‐reperfusion injury via regulating NR2B‐ERK/CREB signalingXialing Tang0Shanshan Xie1Huajun Wang2Yingbin Li3Zhiyu Lai4Shuangxi Sun5Ruanhuan Pan6Yan Huang7Jun Cai8The Second Institute of Clinical Medicine Guangzhou University of Chinese Medicine Guangzhou ChinaThe Second Institute of Clinical Medicine Guangzhou University of Chinese Medicine Guangzhou ChinaThe Second Institute of Clinical Medicine Guangzhou University of Chinese Medicine Guangzhou ChinaThe Second Institute of Clinical Medicine Guangzhou University of Chinese Medicine Guangzhou ChinaThe Second Institute of Clinical Medicine Guangzhou University of Chinese Medicine Guangzhou ChinaThe Second Institute of Clinical Medicine Guangzhou University of Chinese Medicine Guangzhou ChinaThe Second Institute of Clinical Medicine Guangzhou University of Chinese Medicine Guangzhou ChinaThe Second Institute of Clinical Medicine Guangzhou University of Chinese Medicine Guangzhou ChinaThe Second Institute of Clinical Medicine Guangzhou University of Chinese Medicine Guangzhou ChinaAbstract Background and purpose Cerebral ischemia‐reperfusion (I/R) injury is a major factor underlying the high mortality and morbidity rates in stroke patients. Our previous study found that the combination of Astragalus membranaceus extract and ligustrazine (Ast+Lig) treatment could protect brain tissues against inflammation in rats with thrombolytic cerebral ischemia. Activation of N‐methyl‐D‐aspartate receptors (NMDAR) is implicated in brain damage induced by cerebral I/R injury. Methods We used in vivo and in vitro models of cerebral I/R injury for middle cerebral artery occlusion/reperfusion in mice and oxygen‐glucose deprivation/reoxygenation in primary rat cerebral cortical neurons to evaluate the protective effects of Ast+Lig on cerebral I/R injury, and whether the protective mechanism was related to the regulation of NMDAR‐ERK/CREB signaling. Results Treatment with Ast+Lig, or MK‐801 (an inhibitor of NMDAR) significantly ameliorated neurological deficits, decreased infarct volumes, suppressed neuronal damage and Ca2+ influx, and maintained the mitochondrial membrane potential in vivo and in vitro following cerebral I/R injury based on 2,3,5‐triphenyl tetrazolium chloride staining, immunohistochemistry, and immunofluorescent staining. Furthermore, treatment with Ast+Lig evidently prevented the upregulation of NR2B, but not NR2A, in vivo and in vitro following cerebral I/R injury based on western blotting and reverse transcription‐quantitative PCR analyses. Moreover, treatment with Ast+Lig significantly increased the phosphorylation of ERK and CREB, as well as increasing their mRNA expression levels in vivo and in vitro following cerebral I/R injury. Conclusions The overall results thus suggest that the Ast+Lig combination conferred neuroprotective properties against cerebral I/R injury via regulation of the NR2B‐ERK/CREB signaling pathway.https://doi.org/10.1002/brb3.2867Astragalus membranaceuscerebral ischemia‐reperfusion injuryligustrazineN‐methyl‐D‐aspartate receptorsstroke |
| spellingShingle | Xialing Tang Shanshan Xie Huajun Wang Yingbin Li Zhiyu Lai Shuangxi Sun Ruanhuan Pan Yan Huang Jun Cai The combination of Astragalus membranaceus and ligustrazine mitigates cerebral ischemia‐reperfusion injury via regulating NR2B‐ERK/CREB signaling Brain and Behavior Astragalus membranaceus cerebral ischemia‐reperfusion injury ligustrazine N‐methyl‐D‐aspartate receptors stroke |
| title | The combination of Astragalus membranaceus and ligustrazine mitigates cerebral ischemia‐reperfusion injury via regulating NR2B‐ERK/CREB signaling |
| title_full | The combination of Astragalus membranaceus and ligustrazine mitigates cerebral ischemia‐reperfusion injury via regulating NR2B‐ERK/CREB signaling |
| title_fullStr | The combination of Astragalus membranaceus and ligustrazine mitigates cerebral ischemia‐reperfusion injury via regulating NR2B‐ERK/CREB signaling |
| title_full_unstemmed | The combination of Astragalus membranaceus and ligustrazine mitigates cerebral ischemia‐reperfusion injury via regulating NR2B‐ERK/CREB signaling |
| title_short | The combination of Astragalus membranaceus and ligustrazine mitigates cerebral ischemia‐reperfusion injury via regulating NR2B‐ERK/CREB signaling |
| title_sort | combination of astragalus membranaceus and ligustrazine mitigates cerebral ischemia reperfusion injury via regulating nr2b erk creb signaling |
| topic | Astragalus membranaceus cerebral ischemia‐reperfusion injury ligustrazine N‐methyl‐D‐aspartate receptors stroke |
| url | https://doi.org/10.1002/brb3.2867 |
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