Background: Crocin is a known compound with the antioxidant and anti-inflammatory
properties which may help to reduce the progression of neurological disorders. In this study, we
aimed to investigate the protective effects of crocin on beta-amyloid peptide Aβ (1-40) and hydrogen
peroxide (H2O2) induced neurotoxicity in PC12 cells.
Methods: PC12 cells were pretreated with crocin and donepezil (5 and 10 μM) for 2 h and then
treated with Aβ (1-40) (25 μM) for 24 h. In parallel, after pretreatment with crocin (5 and 10 μM) and
donepezil (5 and 10 μM) for 24 h, cells were treated with H2O2 (800 μM) for 4 h. Finally, the cell
viability and intracellular reactive oxygen species (ROS) generation were evaluated using Alamar-
Blue® 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 cytochrome c) cyt c).
Results: Crocin and donepezil could significantly decrease the Aβ toxicity and ROS level. While
treatment with Aβ increased Cyt c release from mitochondria to cytosol, cleaved form of caspase-3
(17 kDa) and activated form of SAPK/JNK p44/4 decreased the activated form of PI3 Kinase P85
protein, indicating that crocin could significantly block the apoptosis initiated with Aβ.
Conclusion: According to the results, crocin could be a promising candidate for further evaluations
against the development of Alzheimer's disease through mitogen-activated protein kinases (MAPK)
and the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling (PI3 K/AKT)