Eclalbasaponin I from Aralia elata (Miq.) Seem. reduces oxidative stress-induced neural cell death by autophagy activation

Biomed Pharmacother. 2018 Jan:97:152-161. doi: 10.1016/j.biopha.2017.10.106. Epub 2017 Nov 6.

Abstract

Oxidative stress has been proposed to contribute to DNA damage and is involved in many neurodegenerative diseases. It has been reported that Aralia elata (Miq.) Seem. (A. elata) exhibits an anti-oxidative effect but the mechanisms underlying this protective effect are still unclear. In this study, six known triterpene saponins were isolated from the buds of A. elata, a well-known medicinal and edible plant in Northeast China. Subsequently, the anti-oxidative effects of all six triterpene saponins were screened by H2O2-induced damage in human neuronblastoma SH-SY5Y cells. Compound 6, also known as Eclalbasaponin I (EcI), was the most potent. Furthermore, the mechanism by which EcI combats H2O2-induced oxidative stress was investigated. The data suggested that EcI could down-regulate apoptosis induction and the generation of reactive oxygen species (ROS) induced by 200μM H2O2 in SH-SY5Y cells. Moreover, EcI increased the activities of antioxidant enzymes such as superoxide dismutase (SOD) and glutathione peroxides (GSH-Px), reduced the levels of malondialdehyde (MDA) to restore the antioxidant defense system, and activated the nuclear factor E2-related factor (Nrf2)/heme oxygenase 1 (HO-1) pathway to combat oxidative stress. In addition, EcI also promoted autophagy during this process. Interestingly, the protective effect was remarkably reversed by autophagy inhibitors, bafilomycin A1 (Baf) or 3-Methyladenine (3-MA). These results demonstrate that autophagy is contribute to the protective effect of EcI. Collectively, our findings provide a new insight into the potential protective effect of EcI by focusing on the role of autophagy.

Keywords: Apoptosis; Oxidative stress; Protective autophagy; Triterpene saponins.

MeSH terms

  • Aralia*
  • Autophagy / drug effects*
  • Autophagy / physiology
  • Cell Death / drug effects
  • Cell Death / physiology
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Cell Survival / physiology
  • Dose-Response Relationship, Drug
  • Humans
  • Neurons / drug effects*
  • Neurons / metabolism
  • Oxidative Stress / drug effects*
  • Oxidative Stress / physiology
  • Plant Components, Aerial
  • Saponins / isolation & purification
  • Saponins / pharmacology*

Substances

  • Saponins
  • eclalbasaponin I