Salvianolic acid B attenuates mitochondrial stress against Aβ toxicity in primary cultured mouse neurons

Biochem Biophys Res Commun. 2018 Apr 15;498(4):1066-1072. doi: 10.1016/j.bbrc.2018.03.119. Epub 2018 Mar 19.

Abstract

Mitochondrial dysfunction is a featured pathology underlying synaptic injury and neuronal stress in Alzheimer's disease (AD). In recent years, the vicious cycle between mitochondrial deficits and intra-neuronal Redox state imbalance has received considerable attention. In this regard, it is of great interest to determine whether antioxidants could alleviate mitochondrial dysfunction in AD-related conditions. Salvianolic acid B (SalB), a bioactive component of alvia miltiorrhiza Bge, is a potent antioxidant. Here we have determined the protective effect of SalB against Aβ-induced mitochondrial abnormalities. Our results showed that the application of SalB substantially alleviated intra-neuronal glutathione (GSH) and lipid oxidation and suppressed excess mitochondrial superoxide generation in Aβ-insulted neurons. Moreover, SalB has demonstrated strong protection on mitochondrial bioenergetics against Aβ toxicity evidenced by preserved mitochondrial membrane potential and ATP production, as well as rescued enzymatic activities of cytochrome C oxidase and F1Fo ATP synthase. In addition, Aβ-induced axonal mitochondrial fragmentation and increased dynamin-like protein 1 phosphorylation at Ser 616 were substantially mitigated by SalB. Lastly, the application of SalB restored synaptic density in Aβ-exposed neurons. The most parsimonious interpretation of the results is that intra-neuronal oxidative stress promotes mitochondrial dysfunction in AD-relevant pathological settings, and SalB has the potential to be a promising agent for AD therapy.

Keywords: Alzheimer's disease; Amyloid beta; Mitochondrial dysfunction; Natural antioxidant; Salvianolic acid B.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / drug therapy
  • Amyloid beta-Peptides / toxicity*
  • Animals
  • Benzofurans / pharmacology*
  • Cells, Cultured
  • Mice
  • Mitochondria / metabolism*
  • Neurons / drug effects
  • Neurons / metabolism*
  • Neurons / ultrastructure
  • Oxidative Stress / drug effects*
  • Protective Agents / pharmacology

Substances

  • Amyloid beta-Peptides
  • Benzofurans
  • Protective Agents
  • salvianolic acid B