<p>Amyloid beta is critically involved in the initiation and progression of Alzheimer’s disease (AD). This peptide is neurotoxic. It can cause cell death by acting on neurons. It can also cause neuronal cell death by acting on glial cells, resulting in the production of toxic and inflammatory molecules, which eventually cause neurotoxicity. In this study, we show that safranal, a compound present in the spice saffron, reduces reactive oxygen species (ROS) and nitric oxide (NO) levels from hippocampal neuronal cells, HT22, treated with oligomeric amyloid beta. It reduces alteration in mitochondrial membrane potential induced by amyloid beta. Safranal shows protective effects against amyloid beta-induced toxicity not only to HT22 cells but also to human neurons. Furthermore, we show that safranal reduces ROS, NO and inflammatory molecule levels from amyloid beta-treated astrocytic cells. Importantly, it provides protection to human neurons from the toxic effects of conditioned medium derived from human astrocytes treated with amyloid beta. Thus, safranal protects neurons against amyloid beta-induced direct and indirect toxicity, suggesting that it could be beneficial in the fight against AD.</p>