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Crocin Protects Against Beta-Amyloid Peptide-Induced Apoptosis in PC12 Cells Via the PI3 K Pathway

[ Vol. 14 , Issue. 4 ]

Author(s):

Reyhaneh Taheri, Elham Hadipour and Zahra Tayarani-Najaran*   Pages 627 - 634 ( 8 )

Abstract:


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) pathways.

Keywords:

Alzheimer's disease, beta-amyloid, crocin, hydrogen peroxide, donepezil, oxidative stress.

Affiliation:

Medical Toxicology Research Center, Mashhad University of Medical Sciences, Mashhad, Targeted Drug Delivery Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Targeted Drug Delivery Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad

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