Senegenin Inhibits Aβ1-42-Induced PC12 Cells Apoptosis and Oxidative Stress via Activation of the PI3K/Akt Signaling Pathway.

Abstract

Background/AimApoptosis and oxidative stress have been considered as key events in the pathogenesis of Alzheimer’s disease (AD). Senegenin (Sen), the major and most effective ingredient of Radix Polygalae, which has anti-apoptotic and anti-oxidative effects. The aim of this study was to investigate the anti-apoptotic and anti-oxidant effects of Sen on Aβ1-42-induced PC12 cells apoptosis and oxidative stress as well as its possible signaling pathway.MethodsRat pheochromocytoma (PC12) cells were treated by 20 μM Aβ1-42 and then divided into 5 different treatment groups (Control; Aβ1-42 20 μM; Aβ1-42 20 μM + Sen 10 μM; Aβ1-42 20 μM + Sen 30 μM; Aβ1-42 20μM + Sen 60 μM). PC12 cells activity was detected by MTT assay. Colony formation assay was performed to assess the clonogenic ability of cells. The cell apoptosis was detected by Annexin-V/PI staining. The pro-apoptotic protein (Bax), anti-apoptotic protein (Bcl-2), anti-oxidative stress factor (HO-1, Nuclear Nrf2, Total Nrf2) and pathway-related protein (Akt, P-Akt, PI3K, P-PI3K) were tested by Western blot. The reactive oxygen species (ROS) level was assessed with a DCFH-DA probe.ResultsThe results indicated that Sen dose-dependently increased cell viability and reduced the number of apoptotic cells. The ratio of P-PI3K/PI3K and P-Akt/Akt increased in a dose-dependent manner under the treatment of Sen, suggesting that Sen might activate the PI3K/Akt signaling pathway. Moreover, Sen upregulates the ratio of Bcl-2/Bax. Further study revealed that Sen can play an antioxidant role in enhancing HO-1, promoting Nrf2 nuclear translocation and reducing ROS accumulation to reduce oxidative stress.ConclusionSen is effective in inhibiting apoptosis and oxidative stress in Aβ1-42-induced PC12 cells, which likely contribute to the development of novel therapies for AD.