P1–412: Evaluation of the neuroprotective effect of salvigenin between the hippocampus and cortex of beta‐amyloid–injected rats

Aggregation of β-amyloid (Aβ) in brain is an important hallmark of Alzheimer's disease. It has been investigated that Aβ induces apoptosis and oxidative stress in neurons. In this study, we evaluated the effect of salvigenin, a natural polyphenolic compound isolated from Salvia Sahendica extract, on the apoptosis and oxidative stress in cortex and hippocampus of Aβ-injected rats. Twenty four adult male albino Wistar rats (weighting 230–260 g) were divided to four groups. Two groups of rats were pretreated by Salvigenin (5mg/kg) for 7 days. Using streotaxic surgery 3 μl of Aβ (10 ng/μl) and/or PBS was injected into the CA1 area. Seven days after surgery, western blot analysis and enzymatic assays on the hippocampus and cortex protein extract were performed to assess apoptosis and oxidative stress pathways. We found that Aβ increased apoptosis factors such as Bax/Bcl-2 ratio, caspase-3 and PARP in hippocampus about 1.6, 3.7 and 1.6 fold, while these inductions had lower magnitude in cortex by 1.2, 2.1 and 1.3 fold compared with sham group. Pretreatment with salvigenin decreased induction of these factors about 1.3, 1.9 and 1.5% in hippocampus and about 1.1, 1.6 and 1.2% in cortex compared to Aβ group. Also we found that Aβ increased Nrf-2 and HO-1 by 1.2 and 1.5 fold in hippocampus and by 1.1 and 1.2 fold in cortex compared with control and Pretreatment with salvigenin decreased the level of HO-1 about 1.2 and 1.1% in hippocampus and cortex despite that Nrf-2 showed more increase (about 1.1 fold) in hippocampus and cortex compared to Aβ-injected rats. We also determined that Aβ injection decreased SOD and CAT activity in hippocampus but increased these activity in cortex, whereas pretreatment with salvigenin prevented the decrease of enzyme activity in hippocampus. In conclusion, salvigenin as a neuroprotective compound inhibits apoptosis and oxidative stress with different magnitude in the hippocampus and cortex of Aβ-injected rats. In fact, the hippocampus has a lower content of antioxidant defenses and cortex is physiologically more exposed to ROS, and therefore has more effective antioxidant defenses.