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https://irlib.pccu.edu.tw/handle/987654321/22936
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| 題名: | Andrographolide Inhibits PI3K/AKT-Dependent NOX2 and iNOS Expression Protecting Mice against Hypoxia/Ischemia-Induced Oxidative Brain Injury |
| 作者: | Chern, Chang-Ming
Liou, Kuo-Tong
Wang, Yea-Hwey
Liao, Jyh-Fei
Yen, Jiin-Cherng
Shen, Yuh-Chiang |
| 貢獻者: | 國術系 |
| 關鍵詞: | LIPOPOLYSACCHARIDE
NF-KAPPA-B
HYPOXIA-INDUCIBLE FACTOR-1
CEREBRAL-ISCHEMIA
REPERFUSION INJURY
SIGNALING PATHWAY
NITRIC-OXIDE;ACTIVATION
STROKE
RAT |
| 日期: | 2011-10 |
| 上傳時間: | 2012-09-06 15:51:34 (UTC+8) |
| 摘要: | 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. |
| 關聯: | Source: PLANTA MEDICA Volume: 77 Issue: 15 Pages: 1669-1679 |
| 顯示於類別: | [技擊運動暨國術學系] 期刊論文
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