Astragaloside IV attenuates the H2O2-induced apoptosis of neuronal cells by inhibiting α-synuclein expression via the p38 MAPK pathway.

Abstract

An oxidative stress insult is one of the principal causes of Parkinson's disease. Astragaloside IV (AS-IV), a constituent extracted from Astragalus membranaceus, has been demonstrated to exert antioxidant effects. However, the mechanisms responsible for the antioxidant properties and neuroprotective effects of AS-IV remain unclear. In this study, we examined the protective effects of AS-IV against the apoptosis of human neuronal cells (SH-SY5Y cells) induced by hydrogen peroxide (H2O2). The results revealed that AS-IV pre-treatment attenuated the H2O2‑induced loss of SH-SY5Y cells in a dose-dependent manner; AS-IV exerted significant protecitve effects by decreasing the apoptotic ratio and attenuating reactive oxygen species overproduction in H2O2-exposed SH-SY5Y cells. By means of immunofluorescence staining, AS-IV was found to decrease the expression of α-synuclein and to increase the expression of tyrosine hydroxylase (TH) in the cells, which had been increased and decreased, respectively by H2O2. As shown by western blot analysis, the protective effects of AS-IV against SH-SY5Y cell injury induced by H2O2 were also mediated via the downregulation of the ratio of Bax/Bcl-2. We found that the neuroprotective effects of AS-IV were associated with the inhibition of the expression of the α-synuclein via the p38 mitogen-activated protein kinase (MAPK) signalling pathway. On the whole, our results suggest that AS-IV exerts protective effects against neurodegenerative diseases by targeting α-synuclein or TH.

• Authors: Xiang Liu, Jun Zhang, Shibo Wang, Jinfu Qiu, Chao Yu
• Journal: International journal of molecular medicine (Int J Mol Med) Vol. 40 Issue 6 Pg. 1772-1780 (Dec 2017) ISSN: 1791-244X [Electronic] Greece
• PMID: 29039448 (Publication Type: Journal Article)

Chemical References

• Antioxidants
• Reactive Oxygen Species
• Saponins
• Triterpenes
• alpha-Synuclein
• astragaloside A
• Hydrogen Peroxide
• p38 Mitogen-Activated Protein Kinases

Topics

• Antioxidants (pharmacology)
• Apoptosis (drug effects)
• Cell Line
• Humans
• Hydrogen Peroxide (toxicity)
• Neurons (cytology, drug effects, metabolism)
• Oxidative Stress (drug effects)
• Reactive Oxygen Species (metabolism)
• Saponins (pharmacology)
• Triterpenes (pharmacology)
• alpha-Synuclein (metabolism)
• p38 Mitogen-Activated Protein Kinases (metabolism)