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.
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