Pharmacological profiling of cyclotides from the medicinal herb clitoria ternatea for therapeutic applications

• Main Author: Nguyen Thi Kim Ngan
• Other Authors: School of Biological Sciences
• Format: Theses and Dissertations
• Language: English
• Published: 2015
• Subjects: DRNTU::Science::Biological sciences
• Online Access: http://hdl.handle.net/10356/65437
• Institution: Nanyang Technological University

Cyclotides are plant-derived, cyclic miniproteins with three interlocking disulfide bonds that have attracted great interests from researchers because of their potential as candidates for novel peptide therapeutics. Cyclotides are highly resistant against thermal, chemical and enzymatic degradation. In this project, we investigate the biological activities and pharmacokinetics of cliotides, which are cyclotides from the butterfly pea Clitoria ternatea, a well-known traditional Indian Ayurverdic herbal medicine with various therapeutic benefits. Cliotides display potent antibacterial activity specifically towards Gram-negative bacteria with minimal inhibitory concentrations of as low as 0.5 IJM. They are cytotoxic against cancer cells with ICso values at low IJM range. Remarkably, cliotides display prominent immunomodulatory activity by enhancing the secretion of cytokines and chemokines at concentration as low as 40 nM in human monocytes in both resting and LPS-stimulated states. We also develop an analytical platform using quantitative proteomic techniques to study pharmacokinetic behavior of cliotides in rats. We show that cliotides have relatively long elimination half-life of 2-20 hr, as compared to a few minutes for conventional peptide and protein drugs; and their kinetics follows the two-compartment model. These findings suggest cliotides constitute one of the active principles in C. ternatea and hence serve as potential candidates for novel therapeutics development.