دورية أكاديمية
Andrographolide Inhibits PI3K/AKT-Dependent NOX2 and iNOS Expression Protecting Mice against Hypoxia/Ischemia-Induced Oxidative Brain Injury
| العنوان: | Andrographolide Inhibits PI3K/AKT-Dependent NOX2 and iNOS Expression Protecting Mice against Hypoxia/Ischemia-Induced Oxidative Brain Injury |
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| المؤلفون: | Chern, C.M., Liou, K.T., Wang, Y.H., Liao, J.F., Yen, J.C., Shen, Y.C. |
| سنة النشر: | 2011 |
| المجموعة: | National Chung Hsing University Institutional Repository - NCHUIR / 國立中興大學 |
| مصطلحات موضوعية: | andrographolide, HIF-1 alpha, hypoxia, iNOS, gp91NADPH oxidase (NOX2), phosphatidylinositol-3-kinase (PI3K)/AKT, nf-kappa-b, hypoxia-inducible factor-1, cerebral-ischemia, reperfusion, injury, signaling pathway, nitric-oxide, activation, stroke, rat, lipopolysaccharide |
| الوصف: | This study aimed to explore the mechanisms by which andrographolide protects against hypoxia-induced oxidative/nitrosative brain injury provoked by cerebral ischemic/reperfusion (CI/R) injury in mice. Hypoxia in vitro was modeled using oxygen-glucose deprivation (OGD) followed by reoxygenation of BV-2 microglial cells. Our results showed that treatment of mice that have undergone CI/R injury with andrographolide (10-100 mu g/kg, i.v.) at 1 h after hypoxia ameliorated CI/R-induced oxidative/nitrosative stress, brain infarction, and neurological deficits in the mice, and enhanced their survival rate. CI/R induced a remarkable production in the mouse brains of reactive oxygen species (ROS) and a significant increase in protein nitrosylation ; this primarily resulted from enhanced expression of NADPH oxidase 2 (NOX2), inducible nitric oxide synthase (iNOS), and the infiltration of CD11b cells due to activation of nuclear factor-kappa B (NF-kappa B) and hypoxia-inducible factor 1-alpha (HIF-1 alpha). All these changes were significantly diminished by andrographolide. In BV-2 cells, OGD induced ROS and nitric oxide production by upregulating NOX2 and iNOS via the phosphatidylinositol-3-kinase (PI3K)/AKT-dependent NF-kappa B and HIF-1 alpha pathways, and these changes were suppressed by andrographolide and LY294002. Our results indicate that andrographolide reduces NOX2 and iNOS expression possibly by impairing PI3K/AKT-dependent NF-kappa B and HIF-1 alpha activation. This compromises microglial activation, which then, in turn, mediates andrographolide's protective effect in the CI/R mice. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| تدمد: | 0032-0943 |
| العلاقة: | #PLACEHOLDER_PARENT_METADATA_VALUE#; Planta Medica; Planta Medica, Volume 77, Issue 15, Page(s) 1669-1679.; http://dx.doi.org/10.1055/s-0030-1271019Test; http://hdl.handle.net/11455/71097Test |
| DOI: | 10.1055/s-0030-1271019 |
| الإتاحة: | https://doi.org/10.1055/s-0030-1271019Test http://hdl.handle.net/11455/71097Test |
| حقوق: | none |
| رقم الانضمام: | edsbas.8D5A723A |
| قاعدة البيانات: | BASE |
| تدمد: | 00320943 |
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| DOI: | 10.1055/s-0030-1271019 |