The protective effects of coumestrol against amyloid-beta peptide- and lipopolysaccharide-induced toxicity on mice astrocytes

Man Hai Liu, Fon Yih Tsuang, Shiow Yunn Sheu, Jui Sheng Sun, Chi Ming Shih

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Objectives: Estrogen replacement therapy can decrease the risk of developing Alzheimer's disease. Phytoestrogens have been proposed as potential alternatives to estrogen replacement therapy. The purpose of this study was to evaluate the in vitro protective effects of coumestrol on mice astrocytes. Methods: Different concentrations of coumestrol were tested for their protective efficacy against two toxic insults, lipopolysaccharide (LPS) and amyloid-beta peptide, on astrocytes. The mitochondrial activity of astrocytes was determined, and the protective efficacy and pathway were examined by their specific gene expression and protein change. Results: The results showed that coumestrol induced a modest but significant increase in viability of astrocytes, while the viability of astrocytes was reduced following exposure to LPS and amyloid-beta peptide. The addition of coumestrol could reverse the toxic effect induced by LPS and amyloid-beta peptide. Both the LPS and amyloid-beta peptide enhanced interleukin 1, interleukin 6, and tumor necrosis factor-alpha synthesis and these effects were inhibited by 10 -9M coumestrol. This effect was more obvious on the LPS-induced inflammation. The estrogen receptor expression was upregulated by coumestrol, while the effect was more obvious on estrogen receptor-beta (ER-beta). These effects can be inhibited by extracellular signal-regulated kinase and c-Jun N-terminal kinase inhibitors but not p38 inhibitor. Discussion: The current data support a possible role for astrocytes in the mediation of neuroprotection by coumestrol. An indirect extracellular signal-regulated kinase/c-Jun N-terminal kinase signaling pathway to downregulate the expression of interleukin 1, interleukin 6, and the tumor necrosis factor-alpha cytotoxic effect may act in concert with the proposed direct ER-beta biosynethsis pathway to achieve a widespread, global protection of ER-beta positive neurons.

Original languageEnglish
Pages (from-to)663-672
Number of pages10
JournalNeurological Research
Volume33
Issue number6
DOIs
Publication statusPublished - Jul 2011

Fingerprint

Coumestrol
Amyloid beta-Peptides
Astrocytes
Lipopolysaccharides
Estrogen Receptor beta
Estrogen Replacement Therapy
JNK Mitogen-Activated Protein Kinases
Poisons
Extracellular Signal-Regulated MAP Kinases
Interleukin-1
Interleukin-6
Tumor Necrosis Factor-alpha
Phytoestrogens
Estrogen Receptors
Alzheimer Disease
Down-Regulation
Inflammation
Gene Expression
Neurons

Keywords

  • Amyloid-beta peptide
  • Astrocyts
  • Coumestrol
  • Lipopolysaccharide

ASJC Scopus subject areas

  • Clinical Neurology
  • Neurology

Cite this

The protective effects of coumestrol against amyloid-beta peptide- and lipopolysaccharide-induced toxicity on mice astrocytes. / Liu, Man Hai; Tsuang, Fon Yih; Sheu, Shiow Yunn; Sun, Jui Sheng; Shih, Chi Ming.

In: Neurological Research, Vol. 33, No. 6, 07.2011, p. 663-672.

Research output: Contribution to journalArticle

Liu, Man Hai ; Tsuang, Fon Yih ; Sheu, Shiow Yunn ; Sun, Jui Sheng ; Shih, Chi Ming. / The protective effects of coumestrol against amyloid-beta peptide- and lipopolysaccharide-induced toxicity on mice astrocytes. In: Neurological Research. 2011 ; Vol. 33, No. 6. pp. 663-672.
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abstract = "Objectives: Estrogen replacement therapy can decrease the risk of developing Alzheimer's disease. Phytoestrogens have been proposed as potential alternatives to estrogen replacement therapy. The purpose of this study was to evaluate the in vitro protective effects of coumestrol on mice astrocytes. Methods: Different concentrations of coumestrol were tested for their protective efficacy against two toxic insults, lipopolysaccharide (LPS) and amyloid-beta peptide, on astrocytes. The mitochondrial activity of astrocytes was determined, and the protective efficacy and pathway were examined by their specific gene expression and protein change. Results: The results showed that coumestrol induced a modest but significant increase in viability of astrocytes, while the viability of astrocytes was reduced following exposure to LPS and amyloid-beta peptide. The addition of coumestrol could reverse the toxic effect induced by LPS and amyloid-beta peptide. Both the LPS and amyloid-beta peptide enhanced interleukin 1, interleukin 6, and tumor necrosis factor-alpha synthesis and these effects were inhibited by 10 -9M coumestrol. This effect was more obvious on the LPS-induced inflammation. The estrogen receptor expression was upregulated by coumestrol, while the effect was more obvious on estrogen receptor-beta (ER-beta). These effects can be inhibited by extracellular signal-regulated kinase and c-Jun N-terminal kinase inhibitors but not p38 inhibitor. Discussion: The current data support a possible role for astrocytes in the mediation of neuroprotection by coumestrol. An indirect extracellular signal-regulated kinase/c-Jun N-terminal kinase signaling pathway to downregulate the expression of interleukin 1, interleukin 6, and the tumor necrosis factor-alpha cytotoxic effect may act in concert with the proposed direct ER-beta biosynethsis pathway to achieve a widespread, global protection of ER-beta positive neurons.",
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