Background: Crocin is a known compound with antioxidant and anti-inflammatory property which many 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 pretreated with crocin and donepezil (5 and 10 µM) for 2 h 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 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 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 and decreased the activated form of PI3 Kinase P85 protein, crocin could significantly block the
apoptosis initiated with Aβ.
Conclusions: According to the results crocin could be a promising candidate for further evaluations against the
development of Alzheimer's diseases through mitogen-activated protein kinases (MAPK) and the phosphatidylinositol
3-kinase (PI3K)/protein kinase B (AKT) signaling (PI3 K/AKT) pathways.