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

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

Volume: 14

Author(s): Reyhaneh Taheri, Elham Hadipour and Zahra Tayarani-Najaran*

Affiliation:

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

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

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.

Cite this article as:

Taheri Reyhaneh , Hadipour Elham and Tayarani-Najaran Zahra *, Crocin Protects Against Beta-Amyloid Peptide-Induced Apoptosis in PC12 Cells Via the PI3 K Pathway, Current Molecular Pharmacology 2021; 14 (4) . https://dx.doi.org/10.2174/1874467213666201012160401