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Radix Scrophulariae extracts (harpagoside) suppresses hypoxia-induced microglial activation and neurotoxicity.

ABSTRACT: 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.In this study, primary microglia cells harvested from neonatal ICR mice were activated by exposure to hypoxia (1 % O2 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? and IL-6 genes) and NO synthesis were also examined.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? 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? (HIF-1?) significantly increase, while the cytosol I?B-? content decreases; these effects can be reversed by 1 h's pre-incubation of 10(-8) M harpagoside. Harpagoside could decrease I?B-? protein phosphorylation and inhibit p65 protein translocation from the cytosol to the nucleus, thus suppress NF-?B activation and reduce the HIF-1? generation.These results suggested that the anti-inflammatory mechanism of harpagoside might be associated with the NF-?B signaling pathway. Harpagoside protect against hypoxia-induced toxicity on microglial cells through HIF-? pathway.

SUBMITTER: Sheu SY

PROVIDER: S-EPMC4570756 | biostudies-literature | 2015 Sep

REPOSITORIES: biostudies-literature

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Radix Scrophulariae extracts (harpagoside) suppresses hypoxia-induced microglial activation and neurotoxicity.

Sheu Shiow-Yunn SY Hong Yi-Wen YW Sun Jui-Sheng JS Liu Man-Hai MH Chen Ching-Yun CY Ke Cherng-Jyh CJ

BMC complementary and alternative medicine 20150914

<h4>Background</h4>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.<h4>Methods</h4>In this study, primary microglia cells harvested from neonatal ICR mice were activated by exposure to hypoxia (1 % O2 for 3 h). Harpagoside had been shown to be no cy ...[more]

PMID: 26370415

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Dataset Information

Radix Scrophulariae extracts (harpagoside) suppresses hypoxia-induced microglial activation and neurotoxicity.

Publications

Radix Scrophulariae extracts (harpagoside) suppresses hypoxia-induced microglial activation and neurotoxicity.

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