Protective role of phenylethanoid glycosides, Torenoside�B and Savatiside A, in Alzheimer's disease

Abstract

The current study assessed the efficacy of two phenylethanoid glycosides (PhGs), Torenoside B (TB) and Savatiside A (SA), in the treatment of Alzheimer's disease (AD). The effects of TB and SA compounds were first assessed following amyloid beta (Aβ)(25-35) induction in SH-SY5Y cells at a range of concentrations. Their effects on cell viability and reactive oxygen species (ROS) were determined by performing MTT and dichlorofluorescin diacetate assays, respectively. The concentration of intracellular Ca(2+) was determined using Fluo-3AM to stain SH-SY5Y cells. SA and TB treatments were also assessed in Aβ(25-35)-induced mice. Y-maze and Morris water maze methods were utilized to assess murine learning and memory capability. The pathological changes of murine hippocampi was determined using H&E and Nissl staining. In addition, biochemical parameters associated with intracellular reactive oxygen pathways including Maleic dialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), acetylcholinesterase (AChE) and Calnexin were also assessed. TB and SA treatment in Aβ(25-35)-induced SH-SY5Y cells resulted in the restoration of cell morphology, an increase of SOD and GSH-Px activity, a decrease in ROS, Ca(2+) and MDA content, and a decrease in Calnexin expression. Furthermore, SA or TB treatment administered to Aβ(25-35)-induced mice improved their spatial/non-spatial learning and memory capabilities. The efficacy of treatment was also supported by a marked change in the morphological structure of pyramidal neurons in the CA1 areas of murine hippocampi, as well as an increase of SOD and GSH-Px activity. Treatment also resulted in a decrease in MDA content, AchE activity and Calnexin expression in murine hippocampal tissue. As potential AD treatment drugs, SA and TB compounds have been demonstrated to alleviate the oxidative stress induced by Aβ(25-35) via the regulation of intracellular calcium homeostasis and Calnexin, preventing AD development.