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

Abstract

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 (Aβ) and hydrogen peroxide (H2O2) in PC12 cells as an appropriate model of Alzheimer's cell damage. PC12 cells pretreated with saffron extract (2.5-40μg/ml), essential oil (2.5-40μg/ml), safranal (2.5-5-40μM) and donepezil (5, 10 and 20μM) for 120min. Then exposed to either Aβ (25μM) for 48h or H2O2 (150μM) 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 5μM) and donepezil (10 and 20μM) significantly decreased the Aβ toxicity. The ROS significantly attenuated when cells pretreated with essential oil, saffron extract, safranal, and donepezil. Cell apoptosis significantly increased after treatment with Aβ (25-35) (25μM) compared to control. However, after pretreatment with safranal (2.5μM) apoptosis was significantly reduced. Western blot analysis of PC12 cells showed that 25μM Aβ (25-35) could increase proteins involved in apoptosis signaling and pretreatment with safranal (2.5μM) 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.