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

Shiow Yunn Sheu, Yi Wen Hong, Jui Sheng Sun, Man Hai Liu, Ching Yun Chen, Cherng Jyh Ke

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

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 % 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-1β 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-1β and IL-6 genes) and NO synthesis of microglial cells. Under 3 h' hypoxic stimulation, the nuclear contents of p65 and hypoxia inducible factor-1aα (HIF-1aα) significantly increase, while the cytosol IkB-aα content decreases; these effects can be reversed by 1 h's pre-incubation of 10-8 M harpagoside. Harpagoside could decrease IkB-aα protein phosphorylation and inhibit p65 protein translocation from the cytosol to the nucleus, thus suppress NF-kB activation and reduce the HIF-1aα generation. Conclusion: These results suggested that the anti-inflammatory mechanism of harpagoside might be associated with the NF-kB signaling pathway. Harpagoside protect against hypoxia-induced toxicity on microglial cells through HIF-aα pathway.

Original languageEnglish
Article number324
JournalBMC Complementary and Alternative Medicine
Volume15
Issue number1
DOIs
Publication statusPublished - Sep 14 2015

Fingerprint

Scrophularia
Microglia
NF-kappa B
Interleukin-1
Cytosol
Interleukin-6
Cell Proliferation
Gene Expression
Hypoxia
harpagoside
Inbred ICR Mouse
Protein Transport
Genes
Anti-Inflammatory Agents

Keywords

  • Activation
  • Anti-inflammation
  • Harpagoside
  • Hypoxia
  • Microglial cells

ASJC Scopus subject areas

  • Complementary and alternative medicine

Cite this

Radix Scrophulariae extracts (harpagoside) suppresses hypoxia-induced microglial activation and neurotoxicity. / Sheu, Shiow Yunn; Hong, Yi Wen; Sun, Jui Sheng; Liu, Man Hai; Chen, Ching Yun; Ke, Cherng Jyh.

In: BMC Complementary and Alternative Medicine, Vol. 15, No. 1, 324, 14.09.2015.

Research output: Contribution to journalArticle

Sheu, Shiow Yunn ; Hong, Yi Wen ; Sun, Jui Sheng ; Liu, Man Hai ; Chen, Ching Yun ; Ke, Cherng Jyh. / Radix Scrophulariae extracts (harpagoside) suppresses hypoxia-induced microglial activation and neurotoxicity. In: BMC Complementary and Alternative Medicine. 2015 ; Vol. 15, No. 1.
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abstract = "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 {\%} 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-1β 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-1β and IL-6 genes) and NO synthesis of microglial cells. Under 3 h' hypoxic stimulation, the nuclear contents of p65 and hypoxia inducible factor-1aα (HIF-1aα) significantly increase, while the cytosol IkB-aα content decreases; these effects can be reversed by 1 h's pre-incubation of 10-8 M harpagoside. Harpagoside could decrease IkB-aα protein phosphorylation and inhibit p65 protein translocation from the cytosol to the nucleus, thus suppress NF-kB activation and reduce the HIF-1aα generation. Conclusion: These results suggested that the anti-inflammatory mechanism of harpagoside might be associated with the NF-kB signaling pathway. Harpagoside protect against hypoxia-induced toxicity on microglial cells through HIF-aα pathway.",
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N2 - 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 % 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-1β 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-1β and IL-6 genes) and NO synthesis of microglial cells. Under 3 h' hypoxic stimulation, the nuclear contents of p65 and hypoxia inducible factor-1aα (HIF-1aα) significantly increase, while the cytosol IkB-aα content decreases; these effects can be reversed by 1 h's pre-incubation of 10-8 M harpagoside. Harpagoside could decrease IkB-aα protein phosphorylation and inhibit p65 protein translocation from the cytosol to the nucleus, thus suppress NF-kB activation and reduce the HIF-1aα generation. Conclusion: These results suggested that the anti-inflammatory mechanism of harpagoside might be associated with the NF-kB signaling pathway. Harpagoside protect against hypoxia-induced toxicity on microglial cells through HIF-aα pathway.

AB - 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 % 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-1β 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-1β and IL-6 genes) and NO synthesis of microglial cells. Under 3 h' hypoxic stimulation, the nuclear contents of p65 and hypoxia inducible factor-1aα (HIF-1aα) significantly increase, while the cytosol IkB-aα content decreases; these effects can be reversed by 1 h's pre-incubation of 10-8 M harpagoside. Harpagoside could decrease IkB-aα protein phosphorylation and inhibit p65 protein translocation from the cytosol to the nucleus, thus suppress NF-kB activation and reduce the HIF-1aα generation. Conclusion: These results suggested that the anti-inflammatory mechanism of harpagoside might be associated with the NF-kB signaling pathway. Harpagoside protect against hypoxia-induced toxicity on microglial cells through HIF-aα pathway.

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