Ferulago Angulata Methanolic Extract Protects PC12 Cells Against Beta Amyloid Peptide Induced Toxicity

Alzheimer's disease (AD) is an age-dependent neurodegenerative disease. Beta-amyloid peptide (Aβ)- induce neurotoxicity has a pivotal role in AD pathogenesis, therefore modulation of Aβ toxicity is the promising therapeutic approach for control of disease progression. Medicinal plants for having multiple active ingredients are effective in complex diseases such as AD therefore; several studies have been focused on medicinal plants for finding an effective treatment for AD. Ferulago angulata is a medicinal plant with the antioxidant and neuroprotective activity. The present study aims to assess the protective effect of the methanolic extract of Ferulago angulate on Aβ-induced toxicity and oxidative stress in PC12 cells. Methanolic extract of aerial parts of the plant was prepared by maceration method. PC12 cells were cultured according to a standard protocol. PC12 cells were incubated for 24 hours with Aβ alone, and Aβ in combined with various concentrations of the Ferulago angulata extract. Cell viability was determined by the MTT assay. Also, ROS production and the activity of Acetylcholine esterase (AChE), glutathione peroxidase (GPx), and caspase-3 enzymes were measured. The extract dose-dependently protects PC12 cells against Aβ-induced cell death. Also, Aβ increases the ROS production, AChE, and caspase-3 activity and decreases the GPx activity, which all were ameliorated by Ferulago angulata extract. Results of the present study indicate that Ferulago angulata extract protects against Aβ-induced oxidative stress and apoptosis. These effects may be due to the antioxidant and anticholinesterase activity of the extract. It is recommended Ferulago angulata extract be investigated more as an anti-Alzheimer agent.

Peptide-Based Vaccines for Neurodegenerative Diseases: Recent Endeavors and Future Perspectives

The development of peptide-based vaccines for treating human neurodegenerative diseases has been the eventual aim of many research endeavors, although no active immunotherapies have been approved for clinical use till now. A typical example of such endeavors is the effort to develop vaccines for Alzheimer’s disease based on the beta-amyloid peptide, which continues to be intensively investigated despite previous setbacks. In this paper, recent developments in peptide-based vaccines which target beta-amyloid as well as tau protein and α-synuclein are presented. Particular focus has been directed toward peptide epitopes and formulation systems selected/developed and employed to enhance vaccine efficacy and safety. Results from both, human clinical trials and animal preclinical studies conducted mainly in transgenic mice have been included. Future perspectives on the topic are also briefly discussed.

Crocin protects against beta-amyloid peptide-induced apoptosis in PC12 cells via PI3 K pathway

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.