Safranal protects against beta-amyloid peptide-induced cell toxicity in PC12 cells via MAPK and PI3 K pathways

Alzheimer's disease is a type of cerebrovascular problem with progressive mental disabilities for the patient. This study aimed to investigate the protective effect of safranal on toxicity and oxidative damage induced by beta-amyloid (A) and hydrogen peroxide (H2O2) in PC12 cells as an appropriate model of Alzheimer's cell damage. PC12 cells pretreated with saffron extract (2.5-40g/ml), essential oil (2.5-40g/ml), safranal (2.5-5-40M) and donepezil (5, 10 and 20M) for 120min. Then exposed to either A (25M) for 48h or H2O2 (150M) for 24h. In the end, the cell survival and intracellular reactive oxygen species (ROS) production analyzed. The anti-apoptotic effects of safranal in PC12 cells were studied using flow cytometry after PI staining. Also, western blot analysis of Cyt c, survivin, p44/42 MAPK (ERK1/2), Phospho-p44/42 MAPK (ERK1/2), PI3 Kinase P85, Phospho-PI3 Kinase P85, phospho SAPK/JNK, SAPK/JNK and caspase 3 performed for detection of apoptosis. Safranal (2.5 and 5M) and donepezil (10 and 20M) significantly decreased the A toxicity. The ROS significantly attenuated when cells pretreated with essential oil, saffron extract, safranal, and donepezil. Cell apoptosis significantly increased after treatment with A ((25-35)) (25M) compared to control. However, after pretreatment with safranal (2.5M) apoptosis was significantly reduced. Western blot analysis of PC12 cells showed that 25M A ((25-35)) could increase proteins involved in apoptosis signaling and pretreatment with safranal (2.5M) could decrease the apoptosis. According to the results, safranal showed anti-apoptotic and antioxidant effects and may exert promising potential for the prevention of Alzheimer's disease.