Crocin protects against beta-amyloid peptide-induced apoptosis in PC12 cells via MAPK and PI3 K pathways

Objective: Alzheimer s disease is a neurological disorder in which brain cell death led to memory loss and cognitive decline. Crocin is a known compound with antioxidant and anti-inflammatory property. This study aimed to investigate the protective effect of crocin on toxicity and oxidative damage induced by Aβ and hydrogen peroxide (H2O2) in PC12 cells as an appropriate model of Alzheimer s cell damage.Materials and Methods: PC12 cells pretreated with crocin and donepezil (5 and 10 μM) for 2 h and then exposed to Aβ (1-40) (25 μM) for 24 h and 48 h. In parallel after pretreatment with crocin and donepezil (5, 10 and 20 μM) for 24 h cells were exposed to H2O2 (800 μM) for 4 h. At the end, the cell survival rate and intracellular reactive oxygen species (ROS) production in both periods were evaluated using AlamarBlue® and 2 , 7 -dichlorodihydrofluorescein diacetate (DCFH-DA), respectively. The western blot test was done to compare the protein level of phospho SAPK/JNK, SAPK/JNK, PI3 Kinase P85, Phospho-PI3 Kinase P85, caspase-3 and Cyt c.Results: Crocin and donepezil could decrease Aβ toxicity and ROS level significantly compared to the untreated control group. While treatment with Aβ increased the level of Cyt c, cleaved form of caspase-3, activated form of SAPK /JNK p44/4 and decreased activated form of PI3 Kinase P85 protein, crocin could significantly block the apoptosis initiated with Aβ.Conclusion: According to the results crocin could be a promising candidate for further evaluations in the progression of Alzheimer s diseases via MAPK and PI3 K pathways.

کلیدواژه ها:

Alzheimer s disease ، beta-amyloid ، crocin ، hydrogen peroxide ، donepezil ، oxidative stress