Neuroprotective effects of Kukoamine B against hydrogen peroxide-induced apoptosis and potential mechanisms in SH-SY5Y cells

Environ Toxicol Pharmacol. 2015 Jul;40(1):230-40. doi: 10.1016/j.etap.2015.06.017. Epub 2015 Jun 22.

Abstract

Oxidative stress mediates the cell damage in several neurodegenerative diseases, including multiple sclerosis, Alzheimer's disease (AD) and Parkinson's disease (PD). This study aimed at investigating the protective effects of Kukoamine B (KuB) against hydrogen peroxide (H2O2) induced cell injury and potential mechanisms in SH-SY5Y cells. Our results revealed that treatment with KuB prior to H2O2 exposure effectively increased the cell viability, and restored the mitochondria membrane potential (MMP). Furthermore, KuB enhanced the antioxidant enzyme activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) and decreased the malondialdehyde (MDA) content. Moreover, KuB minimized the ROS formation and inhibited mitochondria-apoptotic pathway, MAPKs (p-p38, p-JNK, p-ERK) pathways, but activated PI3K-AKT pathway. In conclusion, we believed that KuB may potentially serve as an agent for prevention of several human neurodegenerative and other disorders caused by oxidative stress.

Keywords: Hydrogen peroxide; Kukoamine B; Neuroprotection; Oxidative stress; SH-SY5Y cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects*
  • Caffeic Acids / pharmacology*
  • Caspase 3 / metabolism
  • Caspase 9 / metabolism
  • Catalase / metabolism
  • Cell Line, Tumor
  • Cytochromes c / metabolism
  • Glutathione Peroxidase / metabolism
  • Humans
  • Hydrogen Peroxide / toxicity*
  • Malondialdehyde / metabolism
  • Matrix Metalloproteinases / metabolism
  • Mitogen-Activated Protein Kinases / metabolism
  • Neuroprotective Agents / pharmacology*
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Reactive Oxygen Species / metabolism
  • Spermine / analogs & derivatives*
  • Spermine / pharmacology
  • Superoxide Dismutase / metabolism

Substances

  • Caffeic Acids
  • Neuroprotective Agents
  • Proto-Oncogene Proteins c-bcl-2
  • Reactive Oxygen Species
  • kukoamine B
  • Spermine
  • Malondialdehyde
  • Cytochromes c
  • Hydrogen Peroxide
  • Catalase
  • Glutathione Peroxidase
  • Superoxide Dismutase
  • Mitogen-Activated Protein Kinases
  • Caspase 3
  • Caspase 9
  • Matrix Metalloproteinases