Disulfide-Rich Cyclic Peptides from Clitoria ternatea Protect against β-Amyloid Toxicity and Oxidative Stress in Transgenic Caenorhabditis elegans

Neurotoxic aggregation of β-amyloid (Aβ) peptides is a hallmark of Alzheimer's disease and increased reactive oxygen species (ROS) is an associated process. In the present study, we report the neuroprotective effects of disulfide-rich, circular peptides from Clitoria ternatea ( C. ternatea ) (butterfly pea) on Aβ-induced toxicity in transgenic Caenorhabditis elegans . Cyclotides (∼30 amino acids long) are a special class of cyclic cysteine knot peptides. We show that cyclotide-rich fractions from different plant tissues delay Aβ-induced paralysis in the transgenic CL4176 strain expressing the human muscle-specific Aβ 1-42 gene. They also improved Aβ-induced chemotaxis defects in CL2355 strain expressing Aβ 1-42 in the neuronal cells. ROS assay suggests that this protection is likely mediated by the inhibition of Aβ oligomerization. Furthermore, Aβ deposits were reduced in the CL2006 strain treated with the fractions. The study shows that cyclotides from C. ternatea could be a source of a novel pharmacophore scaffold against neurodegenerative diseases.