Chaperone Activity and Protective Effect against Aβ-Induced Cytotoxicity of IArtocarpus camansi/I Blanco and IAmaranthus dubius/I Mart. ex Thell Seed Protein Extracts

• Published in: Pharmaceuticals (Basel, Switzerland) Vol. 16; no. 6
• Main Authors: Sanchez-Rodriguez, David, Gonzalez-Figueroa, Idsa, Alvarez-Berríos, Merlis P
• Format: Journal Article
• Language: English
• Published: MDPI AG 01.05.2023
• Subjects: Alzheimer's disease; Amaranthus; Care and treatment; Cell death; Chemical properties; Health aspects; Materia medica, Vegetable; Molecular chaperones; Neuroprotective agents; Pharmacology, Experimental; Plant extracts; Plant proteins; United States
• ISSN: 1424-8247; 1424-8247
• DOI: 10.3390/ph16060820

Alzheimer’s disease (AD) is the most common type of dementia and is listed as the sixth-leading cause of death in the United States. Recent findings have linked AD to the aggregation of amyloid beta peptides (Aβ), a proteolytic fragment of 39–43 amino acid residues derived from the amyloid precursor protein. AD has no cure; thus, new therapies to stop the progression of this deadly disease are constantly being searched for. In recent years, chaperone-based medications from medicinal plants have gained significant interest as an anti-AD therapy. Chaperones are responsible for maintaining the three-dimensional shape of proteins and play an important role against neurotoxicity induced by the aggregation of misfolded proteins. Therefore, we hypothesized that proteins extracted from the seeds of Artocarpus camansi Blanco (A. camansi) and Amaranthus dubius Mart. ex Thell (A. dubius) could possess chaperone activity and consequently may exhibit a protective effect against Aβ[sub.1–40] -induced cytotoxicity. To test this hypothesis, the chaperone activity of these protein extracts was measured using the enzymatic reaction of citrate synthase (CS) under stress conditions. Then, their ability to inhibit the aggregation of Aβ[sub.1–40] using a thioflavin T (ThT) fluorescence assay and DLS measurements was determined. Finally, the neuroprotective effect against Aβ[sub.1–40] in SH-SY5Y neuroblastoma cells was evaluated. Our results demonstrated that A. camansi and A. dubius protein extracts exhibited chaperone activity and inhibited Aβ[sub.1–40] fibril formation, with A. dubius showing the highest chaperone activity and inhibition at the concentration assessed. Additionally, both protein extracts showed neuroprotective effects against Aβ[sub.1–40] -induced toxicity. Overall, our data demonstrated that the plant-based proteins studied in this research work can effectively overcome one of the most important characteristics of AD.