The Protective Effects of Jatrorrhizine on β-Amyloid (25-35)-Induced Neurotoxicity in Rat Cortical Neurons

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by selective neuronal loss, amyloid plaques and neurofibrillary tangles. Oxidative stress may play an important role in the pathogenesis of AD which is associated with the accumulation of β-amyloid (Aβ). Jatrorrhizine (JAT) is a novel tetrahydroisoquinoline alkaloid originally extracted from the Chinese herb coptidis rhizome. Our previous studies showed that JAT protected neuronallike cells against H2O2 -induced toxicity. In this study, we investigated the protective effects of JAT against Aβ25-35- induced cell death in rat cortical neurons. When the cortical neurons were exposed to 25μM Aβ25-35 for 24h, there was a significant reduction in cell viability and activities of SOD and GSH-Px. It also increased the production of malondialdehyde (MDA) and ROS but reduced MMP. Pretreatment of the cortical neurons with various concentrations of JAT (1-10μM) attenuated Aβ25-35-induced neurotoxicity markedly. JAT was also showed to suppress the activation of caspase-3 induced by Aβ25-35 and prevented the cytochrome c transporting into the cytosol. These results indicate that JAT demonstrates the neuroprotective effects against Aβ25-35-induced injury via its antioxidative potential, which may provide a therapeutical potential to AD. Keywords: β-amyloid (25-35), JAT, Alzheimer's disease, oxidative stress, apoptosis, antioxidative potential, malondialdehyde, neurofibrillary tangles, neurotoxicity, cortical neurons.