Salvianolic acid A alleviates ischemic brain injury through the inhibition of inflammation and apoptosis and the promotion of neurogenesis in mice

Salvianolic acid A (SalA), a chemical type of caffeic acid trimer, has drawn great attention for its potent bioactivities against ischemia-induced injury both in vitro and in vivo. In this study, we evaluated SaIA's protective effects against acute ischemic stroke by inducing middle cerebral artery occlusion/reperfusion (MCAO) injuries in mice. Treatment of the mice with SaIA (50 and 100 mu g/kg, i.v.) at 2 h after MCAO enhanced their survival rate, improved their moving activity, and ameliorated the severity of brain infarction and apoptosis seen in the mice by diminishing pathological changes such as the extensive breakdown of the blood-brain barrier (BBB), nitrosative stress, and the activation of an inflammatory transcriptional factor p65 nuclear factor-kappa B (NF-kappa B) and a pro-apoptotic kinase p25/Cdk5. SaIA also intensively limited cortical infarction and promoted the expression of neurogenesis protein near the pen-infarct cortex and subgranular zone of the hippocampal dentate gyms by compromising the activation of GSK3 beta and p25/Cdk5, which in turn upregulated beta-catenin, doublecortin (DCX), and Bcl-2, most possibly through the activation of PI3K/Akt signaling via the upregulation of brain-derived neurotrophic factor. We conclude that SaIA blocks inflammatory responses by impairing NF-kappa B signaling, thereby limiting inflammation/nitrosative stress and preserving the integrity of the BBB; SaIA also concomitantly promotes neurogenesis-related protein expression by compromising GSK3 beta/Cdk5 activity to enhance the expression levels of beta-catenin/DCX and Bcl-2 for neuroprotection. (C) 2016 Elsevier Inc. All rights reserved.