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Naunyn-Schmiedeberg's Archives of Pharmacology

, Volume 391, Issue 2, pp 159–168 | Cite as

Sarsasapogenin suppresses Aβ overproduction induced by high glucose in HT-22 cells

  • Meng-Ya Zhang
  • Yu Li
  • Shen-Yuan Yin
  • Li Kong
  • Xiao-Li Liu
  • Xiao-Xing YinEmail author
  • Yao-Wu LiuEmail author
Original Article
  • 202 Downloads

Abstract

The aim of this study is to investigate effects and potential mechanisms of sarsasapogenin (Sar), an active component purified from Rhizoma Anemarrhenae, on high glucose-induced amyloid-beta (Aβ) peptide overproduction in HT-22 cells. HT-22 cells were divided into normal glucose; high glucose (HG); HG co-treated with low, middle, and high concentration of Sar (1, 5, 25 μmol/L); and peroxisome proliferator-activated receptor γ (PPARγ) agonist (10 μmol/L pioglitazone). After treatment for 24 h, protein expression of Aβ and β-site Aβ precursor protein cleaving enzyme 1 (BACE1) and activated PPARγ level were determined by Western blot; Aβ42 levels were also measured by using both immunofluorescence and ELISA methods. BACE1 activity and mRNA level were assessed by fluorospectrophotometry and quantitative PCR, respectively. Cell viability was assayed with a CCK-8 kit. Elevated Aβ expression and Aβ42 level were found in HG-treated HT-22 cells, accompanied by increased BACE1 protein and mRNA levels as well as enzymatic activity, which was markedly attenuated by three concentrations of Sar and pioglitazone. Moreover, HG reduced nuclear PPARγ levels, which was reversed by middle and high concentrations of Sar as well as pioglitazone. PPARγ antagonist GW9662 (20 μmol/L) pretreatment reversed the effect of Sar on BACE1 protein expression in HG-cultured HT-22 cells. Additionally, Sar suppressed HG-induced decreases in cell viability of HT-22 cells. High glucose can induce an increase in Aβ levels and a decrease in cell viability in HT-22 cells, while co-treatment with Sar improves these results, which is mediated likely through activation of PPARγ and subsequent downregulation of BACE1.

Keywords

Amyloid-beta peptides β-Site Aβ precursor protein cleaving enzyme 1 High glucose Peroxisome proliferator-activated receptor γ Sarsasapogenin 

Notes

Funding information

The work was supported through funding from Qing Lan Project of Jiangsu Province (2014), China, and the Priority Academic Program Development of Jiangsu Higher Education Institutions, China.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2017

Authors and Affiliations

  1. 1.Jiangsu Key Laboratory of New Drug Research and Clinical PharmacyXuzhou Medical UniversityXuzhouChina
  2. 2.Department of Pharmacy, Affiliated Wuxi Children’s HospitalNanjing Medical UniversityWuxiChina
  3. 3.Department of Pharmacology, School of PharmacyXuzhou Medical UniversityXuzhouChina

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