Astragaloside IV ameliorates endoplasmic reticulum stress‑induced apoptosis of Aβ25‑35‑treated PC12 cells by inhibiting the p38MAPK signaling pathway.

Abstract

Endoplasmic reticulum stress (ERS) serves a vital role in the pathological development of Alzheimer's disease (AD). ERS can promote programmed cell death (apoptosis) during AD; however, the specific molecular mechanisms that lead to ERS remain unclear. It is very important that a drug for the treatment of AD is identified. Our previous studies indicated that astragaloside IV (AST IV) has anti-inflammatory effects and helps cells resist oxidative stress. In the present study, western blotting and reverse transcription semi-quantitative polymerase chain reaction were used to detect protein and mRNA expression levels, flow cytometry was used to measure intracellular reactive oxygen species (ROS) levels, and superoxide dismutase (SOD) and malondialdehyde (MDA) activity was detected using commercially available kits. The results demonstrated that SOD activity was decreased, and MDA content, ROS levels, and the expression levels of p38 mitogen-activated protein kinase (MAPK) and ERS-associated proteins, including binding immunoglobulin protein/glucose-regulated protein and growth arrest- and DNA damage -inducible gene 153/C/EBP homologous protein, were increased in amyloid β (Aβ)25-35-treated PC12 cells. Furthermore, to investigate the role of p38 MAPK and the effects of AST IV in an in vitro model of AD, SB203580, a p38 MAPK signaling pathway inhibitor, and AST IV were administered to Aβ25-35-treated PC12 cells. The results revealed that AST IV protected the cells against AD. This effect may be caused by decreases in ROS levels, which may inhibit the p38 MAPK signaling pathway and thereby suppress ERS in Aβ25-35-treated PC12 cells.