標題: Radix Scrophulariae extracts (harpagoside) suppresses hypoxia-induced microglial activation and neurotoxicity
作者: Sheu, Shiow-Yunn
Hong, Yi-Wen
Sun, Jui-Sheng
Liu, Man-Hai
Chen, Ching-Yun
Ke, Cherng-Jyh
智慧型仿生系統研究中心
Biomimetic Systems Research Center
關鍵字: Harpagoside;Hypoxia;Microglial cells;Activation;Anti-inflammation
公開日期: 14-Sep-2015
摘要: Background: Hypoxia could lead to microglia activation and inflammatory mediators' overproduction. These inflammatory molecules could amplify the neuroinflammatory process and exacerbate neuronal injury. The aim of this study is to find out whether harpagoside could reduce hypoxia-induced microglia activation. Methods: In this study, primary microglia cells harvested from neonatal ICR mice were activated by exposure to hypoxia (1 % O-2 for 3 h). Harpagoside had been shown to be no cytotoxicity on microglia cells by MTT assay. The scavenger effect of harpagoside on hypoxia-enhanced microglial cells proliferation, associated inflammatory genes expression (COX-II, IL-1 beta and IL-6 genes) and NO synthesis were also examined. Results: Hypoxia enhances active proliferation of microglial cells, while harpagoside can scavenge this effect. We find that harpagoside could scavenge hypoxia-enhanced inflammatory genes expression (COX-2, IL-1 beta and IL-6 genes) and NO synthesis of microglial cells. Under 3 h' hypoxic stimulation, the nuclear contents of p65 and hypoxia inducible factor-1 alpha (HIF-1 alpha) significantly increase, while the cytosol I kappa B-alpha content decreases; these effects can be reversed by 1 h's pre-incubation of 10(-8) M harpagoside. Harpagoside could decrease I kappa B-alpha protein phosphorylation and inhibit p65 protein translocation from the cytosol to the nucleus, thus suppress NF-kappa B activation and reduce the HIF-1 alpha generation. Conclusion: These results suggested that the anti-inflammatory mechanism of harpagoside might be associated with the NF-kappa B signaling pathway. Harpagoside protect against hypoxia-induced toxicity on microglial cells through HIF-alpha pathway.
URI: http://dx.doi.org/10.1186/s12906-015-0842-x
http://hdl.handle.net/11536/128278
ISSN: 1472-6882
DOI: 10.1186/s12906-015-0842-x
期刊: BMC COMPLEMENTARY AND ALTERNATIVE MEDICINE
Volume: 15
起始頁: 0
結束頁: 0
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