Sarsasapogenin Suppresses A Beta Overproduction Induced By High Glucose In Ht-22 Cells

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 (A beta) 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 mu mol/L); and peroxisome proliferator-activated receptor gamma (PPAR gamma) agonist (10 mu mol/L pioglitazone). After treatment for 24 h, protein expression of A beta and beta-site A beta precursor protein cleaving enzyme 1 (BACE1) and activated PPAR gamma level were determined by Western blot; A beta 42 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 A beta expression and A beta 42 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 PPAR gamma levels, which was reversed by middle and high concentrations of Sar as well as pioglitazone. PPAR gamma antagonist GW9662 (20 mu mol/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 A beta 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 PPAR gamma and subsequent downregulation of BACE1.