Effect of cycloastragenol and punicalagin on Prp(106–126) and Aβ(25–35) oligomerization and fibrillizaton

• Published in: Biophysical chemistry 2023-11, Vol.302, p.107108-107108, Article 107108
• Main Authors: Navale, Govinda R., Chauhan, Rahul, Saini, Saakshi, Roy, Partha, Ghosh, Kaushik
• Format: Article
• Language: English
• Subjects: Alzheimer's disease; Cycloastragenol; Natural products; Prion disease; Punicalagin
• ISSN: 0301-4622; 1873-4200
• DOI: 10.1016/j.bpc.2023.107108

Numerous neurological disorders, including prion, Parkinson's, and Alzheimer's disease (AD), are identified as being caused by alterations in protein conformation, aggregation, and metal ion dyshomeostasis. Recent years have seen a significant increase in the exploration and study of natural products (NPs) from plant and microbial sources for their therapeutic potential against several diseases, including cancer, diabetes, cardiovascular disease, and neurodegenerative diseases. In this study, we have examined the effect of two NPs, cycloastragenol (CAG) and punicalagin (PCG), on the metal-induced oligomerization and aggregation of Aβ25–35 and PrP106–126 peptides. The peptide aggregation and inhibitory properties of both NPs were examined by the thioflavin-T (ThT) assay, MALDI-TOF, circular dichroism (CD) spectroscopy, and transmission electron microscopy (TEM). Among the two NPs, PCG significantly binds to the peptides, chelates metal ions (Cu2+ and Zn2+), inhibits peptide aggregation, substantially reduces oxidative stress, and controls the production of reactive oxygen species (ROS). Both NPs exhibited low cytotoxicity and prominently mitigated peptide-mediated cell cytotoxicity in hippocampal neuronal HT-22 cells by covalent bonding and hydrophobic interactions. [Display omitted] •Cycloastragenol and punicalagin were examined for their anti-aggregation activities.•Alzheimer's Aβ25–35 and prions PrP106–126 peptides were used.•Thioflavin-T, CD-spectra, TEM analysis, MTT assay and MALDI-TOF analysis were performed.•PCG significantly interacts with peptides and inhibits Aβ/PrP peptide oligomerization and fibrilization.•CAG and PCG have less cytotoxicity, protect against amyloid-induced ROS and cell cytotoxicity, and inhibit fibril formation.