Salvianolic acid B attenuates mitochondrial stress against Ab toxicity in primary cultured mouse neurons Yan He a, b , Kun Jia a, b , Lei Li a, b , Qi Wang a, b , Shuhui Zhang c , Jiaming Du c, * , Heng Du a, b, ** a Alzheimer's Disease Center, Shandong Qianfoshan Hospital Affiliated to Shandong University, China b Department of Neurology, Shandong Qianfoshan Hospital Affiliated to Shandong University, China c Department of Cardiology, 2nd Hospital Affiliated to Shandong University of Traditional Chinese Medicine, China article info Article history: Received 5 March 2018 Accepted 14 March 2018 Available online xxx Keywords: Salvianolic acid B Alzheimer's disease Mitochondrial dysfunction Amyloid beta Natural antioxidant 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 inter- est to determine whether antioxidants could alleviate mitochondrial dysfunction in AD-related condi- tions. 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 Ab-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 Ab-insulted neurons. Moreover, SalB has demonstrated strong protection on mitochondrial bioenergetics against Ab 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, Ab-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 Ab-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. © 2018 Elsevier Inc. All rights reserved. 1. Introduction Alzheimer's disease (AD) is a chronic neurodegenerative disor- der characterized by progressive memory loss [1]. Amyloid beta (Ab) is a key mediator of this lethal neurological disease [1 ,2]. In recent years, the crosstalk between mitochondrial deficits and imbalanced Redox state in the development of synaptic failure and neuronal stress in AD has been highlighted [3,4]. It is proposed that Ab-induced mitochondrial reactive oxygen species (ROS) produc- tion and intracellular oxidative stress reinforce each other, thus forming a vicious cycle resulting in devastating oxidative damages and mitochondrial abnormalities. It should be noted that mitochondrial defects have been suggested to be a critical causative factor for synaptic injury and neuronal demise in AD [5,6]. In this context, to extinguish free radicals by using ROS scavengers seems to be protective for mitochondrial function and synaptic plasticity/ activity in Ab-rich milieus. Among the many ROS scavengers, plant- derived antioxidants from natural sources have received consider- able attention, giving their advantages of being less expensive and safety-proven [7]. SalB is a bioactive component purified from the roots of Salvia miltiorrhiza Bge, a traditional Chinese medicine that has been widely used as a potent ROS scavenger for the treatment of car- diovascular diseases, hepatitis and menstrual disorders [8,9]. Although previous studies have implicated the protective effects of SalB against Ab-mediated neuronal stress [10], whether SalB miti- gates mitochondrial dysfunction in AD-related conditions still re- mains unresolved. In this study, we have found that SalB remarkably alleviates Ab-induced excess mitochondrial superoxide * Corresponding author. ** Corresponding author. Alzheimer's Disease Center, Shandong Qianfoshan Hos- pital affiliated to Shandong University, China. E-mail addresses: djm1949@aliyun.com (J. Du), senyaheng@163.com (H. Du). Contents lists available at ScienceDirect Biochemical and Biophysical Research Communications journal homepage: www.elsevier.com/locate/ybbrc https://doi.org/10.1016/j.bbrc.2018.03.119 0006-291X/© 2018 Elsevier Inc. All rights reserved. Biochemical and Biophysical Research Communications xxx (2018) 1e7 Please cite this article in press as: Y. He, et al., Salvianolic acid B attenuates mitochondrial stress against Ab toxicity in primary cultured mouse neurons, Biochemical and Biophysical Research Communications (2018), https://doi.org/10.1016/j.bbrc.2018.03.119