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

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 intraneuronal 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 Sa1B against AP-induced mitochondrial abnormalities. Our results showed that the application of Sa1B substantially alleviated intra-neuronal glutathione (GSH) and lipid oxidation and suppressed excess mitochondrial superoxide generation in AP-insulted neurons. Moreover, Sa1B has demonstrated strong protection on mitochondrial bioenergetics against AP toxicity evidenced by preserved mitochondrial membrane potential and ATP production, as well as rescued enzymatic activities of cytochrome C oxidase and F1 Fo ATP synthase. In addition, AP-induced axonal mitochondrial fragmentation and increased dynamin-like protein 1 phosphorylation at Ser 616 were substantially mitigated by SaIB. Lastly, the application of SalB restored synaptic density in AP-exposed neurons. The most parsimonious interpretation of the results is that intra-neuronal oxidative stress promotes mitochondrial dysfunction in AD-relevant pathological settings, and SaIB has the potential to be a promising agent for AD therapy. (C) 2018 Elsevier Inc. All rights reserved.