Salvianolic acid A (Sal A) is a polyphenol extracted from the root of the Salvia miltiorrhiza bunge. Hydrogen peroxide (H2O2) is a major reactive oxygen species (ROS), which has been implicated in stroke and other neurodegenerative diseases, including Alzheimer's disease and Parkinson's disease. In this study, we investigated the neuroprotective effects of Sal A in human SH-SY5Y neuroblastoma cells against H2O2-induced injury. Our results showed that cells pretreated with Sal A exhibited enhanced neuronal survival and that this protection was associated with an increase in adenosine triphosphate (ATP) and the stabilization of mitochondrial membrane potential. In addition, Sal A markedly decreased the excessive activation AMP-activated protein kinase (AMPK) and the serine-threonine protein kinase, Akt, in SH-SY5Ycells induced by H2O2. In conclusion, our results demonstrated that Sal A protects SH-SY5Y cells against H2O2-induced oxidative stress and these protective effects are related to stress tolerance and not energy depletion via inhibition of the AMPK and Akt signaling pathway. (C) 2012 Elsevier Inc. All rights reserved.