Sodium tanshinone IIA sulfonate protects against Aβ1–42-induced cellular toxicity by modulating Aβ-degrading enzymes in HT22 cells

Abstract

β-Amyloid (Aβ) plays an important role in the pathogenesis of Alzheimer's disease (AD). However, there is still no effective Aβ-targeting drugs for AD treatment. In this study, we explored the effect and mechanism of Sodium Tanshinone IIA Sulfonate (STS) on AD. Aβ-treated HT22 cells, an immortalized mouse hippocampal neuronal cell line, were employed. Different dosages of STS (0.1, 1 and 10 μM) were selected. STS improved cell viability and protected against Aβ-induced apoptosis in a dose-dependent manner. Furthermore, the levels of reactive oxygen species (ROS) and malondialdehyde (MDA) were decreased, while the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were significantly increased after STS treatment. STS decreased the levels of phosphorylate PKR-like (p-PERK), phosphorylate eukaryotic initiation factor 2 (p-eIF2α), phosphorylate inositol-requiring enzyme (p-IRE1α), X-box binding protein 1 (XBP1) and binding immunoglobulin heavy chain protein (Bip), while increased protein disulfide isomerase (PDI) levels in Aβ-treated HT22 cells. In addition, the levels of insulin degrading enzymes (IDE) and Nepterrilysin (NEP) (or call it CD10) were significantly increased after STS treatment. Taken together, these results indicated that STS might be effective in treating AD via increasing the levels of Aβ-degrading enzymes.