Protective effects of fraxin on cerebral ischemia-reperfusion injury by mediating neuroinflammation and oxidative stress through PPAR-γ/NF-κB pathway
Background: Inflammation and oxidative stress are associated with the pathogenesis of cerebral ischemia-reperfusion (I/R) injury. Fraxin, one of the primary active ingredients of Cortex Fraxini, may have potent anti-inflammatory activity. This study intended to investigate the function and mechanism...
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| Format: | Article |
| Language: | English |
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Elsevier
2022-09-01
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| Series: | Brain Research Bulletin |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0361923022001551 |
| _version_ | 1797366637869924352 |
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| author | Hongyan Yao Jianqiang Zhao XiaoYang Song |
| author_facet | Hongyan Yao Jianqiang Zhao XiaoYang Song |
| author_sort | Hongyan Yao |
| collection | DOAJ |
| description | Background: Inflammation and oxidative stress are associated with the pathogenesis of cerebral ischemia-reperfusion (I/R) injury. Fraxin, one of the primary active ingredients of Cortex Fraxini, may have potent anti-inflammatory activity. This study intended to investigate the function and mechanism of fraxin in a middle cerebral artery occlusion (MCAO) model. Methods: A middle cerebral artery occlusion (MCAO) rat model was engineered. Both in-vivo and in-vitro models were dealt with Fraxin. The profiles of inflammation-concerned cytokines, proteins and oxidative stress factors were determined by RT-PCR, western blot, and enzyme-linked immunosorbent assay (ELISA), and neuronal apoptosis and reactive oxygen species (ROS) levels were measured. The neurological functions of rats were evaluated by Morris water maze and modified neurological severity scores (mNSS). Results: The data revealed that fraxin abated the OGD/R-mediated release of inflammatory and oxidative stress mediators, enhanced “M2″-like BV2 microglia polarization, and mitigated HT22 cell apoptosis. Mechanistically, fraxin boosted PPAR-γ expression, activated the Nrf2/HO-1 pathway, and suppressed NF-κB, IKK-β，p38 MAPK, ERK1/2 and Keap1 in a dose-dependent manner. Furthermore, attenuating PPAR-γ through pharmacological treatment with GW9662 (a PPAR-γ antagonist) mainly weakened the neuroprotective and anti-inflammatory functions of fraxin. Conclusion: Fraxin could considerably ameliorate cerebral I/R damage by repressing oxidative stress, inflammatory response, and cell apoptosis through abrogating the PPARγ/ NF-κB pathway. |
| first_indexed | 2024-03-08T17:06:32Z |
| format | Article |
| id | doaj.art-10b5e97a509142c694952d9302913a41 |
| institution | Directory Open Access Journal |
| issn | 1873-2747 |
| language | English |
| last_indexed | 2024-03-08T17:06:32Z |
| publishDate | 2022-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Brain Research Bulletin |
| spelling | doaj.art-10b5e97a509142c694952d9302913a412024-01-04T04:36:12ZengElsevierBrain Research Bulletin1873-27472022-09-011874962Protective effects of fraxin on cerebral ischemia-reperfusion injury by mediating neuroinflammation and oxidative stress through PPAR-γ/NF-κB pathwayHongyan Yao0Jianqiang Zhao1XiaoYang Song2Nursing Department, The Affiliated Hospital of Xi'an Medical University, Shanxi, ChinaDepartment of Nephropathy and Hematology, The First Affiliated Hospital of Xi'an Medical University, Shanxi, ChinaOutpatient Department, The First Affiliated Hospital of Xi'an Medical University, Shanxi, China; Correspondence to: Outpatient Department, The First Affiliated Hospital of Xi'an Medical University, No.48 Fenghao West Road, Tumen Street, Lianhu District, Xi’an 710077, Shanxi, China.Background: Inflammation and oxidative stress are associated with the pathogenesis of cerebral ischemia-reperfusion (I/R) injury. Fraxin, one of the primary active ingredients of Cortex Fraxini, may have potent anti-inflammatory activity. This study intended to investigate the function and mechanism of fraxin in a middle cerebral artery occlusion (MCAO) model. Methods: A middle cerebral artery occlusion (MCAO) rat model was engineered. Both in-vivo and in-vitro models were dealt with Fraxin. The profiles of inflammation-concerned cytokines, proteins and oxidative stress factors were determined by RT-PCR, western blot, and enzyme-linked immunosorbent assay (ELISA), and neuronal apoptosis and reactive oxygen species (ROS) levels were measured. The neurological functions of rats were evaluated by Morris water maze and modified neurological severity scores (mNSS). Results: The data revealed that fraxin abated the OGD/R-mediated release of inflammatory and oxidative stress mediators, enhanced “M2″-like BV2 microglia polarization, and mitigated HT22 cell apoptosis. Mechanistically, fraxin boosted PPAR-γ expression, activated the Nrf2/HO-1 pathway, and suppressed NF-κB, IKK-β，p38 MAPK, ERK1/2 and Keap1 in a dose-dependent manner. Furthermore, attenuating PPAR-γ through pharmacological treatment with GW9662 (a PPAR-γ antagonist) mainly weakened the neuroprotective and anti-inflammatory functions of fraxin. Conclusion: Fraxin could considerably ameliorate cerebral I/R damage by repressing oxidative stress, inflammatory response, and cell apoptosis through abrogating the PPARγ/ NF-κB pathway.http://www.sciencedirect.com/science/article/pii/S0361923022001551FraxinIschemia-reperfusionInflammationOxidative stressApoptosisSignaling pathway |
| spellingShingle | Hongyan Yao Jianqiang Zhao XiaoYang Song Protective effects of fraxin on cerebral ischemia-reperfusion injury by mediating neuroinflammation and oxidative stress through PPAR-γ/NF-κB pathway Brain Research Bulletin Fraxin Ischemia-reperfusion Inflammation Oxidative stress Apoptosis Signaling pathway |
| title | Protective effects of fraxin on cerebral ischemia-reperfusion injury by mediating neuroinflammation and oxidative stress through PPAR-γ/NF-κB pathway |
| title_full | Protective effects of fraxin on cerebral ischemia-reperfusion injury by mediating neuroinflammation and oxidative stress through PPAR-γ/NF-κB pathway |
| title_fullStr | Protective effects of fraxin on cerebral ischemia-reperfusion injury by mediating neuroinflammation and oxidative stress through PPAR-γ/NF-κB pathway |
| title_full_unstemmed | Protective effects of fraxin on cerebral ischemia-reperfusion injury by mediating neuroinflammation and oxidative stress through PPAR-γ/NF-κB pathway |
| title_short | Protective effects of fraxin on cerebral ischemia-reperfusion injury by mediating neuroinflammation and oxidative stress through PPAR-γ/NF-κB pathway |
| title_sort | protective effects of fraxin on cerebral ischemia reperfusion injury by mediating neuroinflammation and oxidative stress through ppar γ nf κb pathway |
| topic | Fraxin Ischemia-reperfusion Inflammation Oxidative stress Apoptosis Signaling pathway |
| url | http://www.sciencedirect.com/science/article/pii/S0361923022001551 |
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