The neuroprotective effects of tanshinone IIA on β-amyloid-induced toxicity in rat cortical neurons.

Oxidative stress caused by amyloid β-peptide (Aβ) may play an important role in the pathogenesis of Alzheimer disease (AD). Aβ is known to be directly responsible for the production of reactive oxygen species (ROS) and induction of apoptosis. Tanshinone IIA (Tan IIA) is extracted from a traditional herbal medicine Salvia miltiorrhiza BUNGE, which has been shown to protect against oxidative stress and cell death. In this study, we investigated the neuroprotective effect of Tan IIA against Aβ₂₅₋₃₅-induced cell death in cultured cortical neurons. Exposure of cortical neurons to 30μM Aβ₂₅₋₃₅ caused a significant viability loss, cell apoptosis and decreased activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) as well as increased levels of malondialdehyde (MDA) production. In parallel, Aβ₂₅₋₃₅ significant increased the intracellular ROS elevation and decreased mitochondrial membrane potential (MMP). However, pretreatment of the cells with Tan IIA prior to Aβ₂₅₋₃₅ exposure suppressed these Aβ₂₅₋₃₅-induced cellular events noticeably. In addition, Tan IIA reduced the Aβ₂₅₋₃₅-induced increase of caspase-3 activity, and reduced cytochrome c translocation into the cytosol from mitochondria. Furthermore, Tan IIA also ameliorated the Aβ₂₅₋₃₅-induced Bcl-2/Bax ratio reduction in cortical neurons. Taken together, these data indicate that Tan IIA protected cultured cortical neurons against Aβ₂₅₋₃₅-induced neurotoxicity through its antioxidative potential. Our results strongly suggest that Tan IIA may be effective in treating AD associated with oxidative stress.