Pharmacological profiling of cyclotides from the medicinal herb clitoria ternatea for therapeutic applications
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 degradat...
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| Other Authors: | |
| Format: | Thesis |
| Language: | English |
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2015
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| Online Access: | http://hdl.handle.net/10356/65437 |
| _version_ | 1811696533746221056 |
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| author | Nguyen Thi Kim Ngan |
| author2 | School of Biological Sciences |
| author_facet | School of Biological Sciences Nguyen Thi Kim Ngan |
| author_sort | Nguyen Thi Kim Ngan |
| collection | NTU |
| description | 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. |
| first_indexed | 2024-10-01T07:40:53Z |
| format | Thesis |
| id | ntu-10356/65437 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T07:40:53Z |
| publishDate | 2015 |
| record_format | dspace |
| spelling | ntu-10356/654372023-02-28T18:47:33Z Pharmacological profiling of cyclotides from the medicinal herb clitoria ternatea for therapeutic applications Nguyen Thi Kim Ngan School of Biological Sciences James P. Tam Peter C. Dedon DRNTU::Science::Biological sciences 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. Doctor of Philosophy (SBS) 2015-09-22T06:22:30Z 2015-09-22T06:22:30Z 2014 2014 Thesis Nguyen Thi Kim Ngan. (2015).Pharmacological profiling of cyclotides from the medicinal herb clitoria ternatea for therapeutic applications. Doctoral thesis, Nanyang Technological University, Singapore. http://hdl.handle.net/10356/65437 en 161 p. application/pdf |
| spellingShingle | DRNTU::Science::Biological sciences Nguyen Thi Kim Ngan Pharmacological profiling of cyclotides from the medicinal herb clitoria ternatea for therapeutic applications |
| title | Pharmacological profiling of cyclotides from the medicinal herb clitoria ternatea for therapeutic applications |
| title_full | Pharmacological profiling of cyclotides from the medicinal herb clitoria ternatea for therapeutic applications |
| title_fullStr | Pharmacological profiling of cyclotides from the medicinal herb clitoria ternatea for therapeutic applications |
| title_full_unstemmed | Pharmacological profiling of cyclotides from the medicinal herb clitoria ternatea for therapeutic applications |
| title_short | Pharmacological profiling of cyclotides from the medicinal herb clitoria ternatea for therapeutic applications |
| title_sort | pharmacological profiling of cyclotides from the medicinal herb clitoria ternatea for therapeutic applications |
| topic | DRNTU::Science::Biological sciences |
| url | http://hdl.handle.net/10356/65437 |
| work_keys_str_mv | AT nguyenthikimngan pharmacologicalprofilingofcyclotidesfromthemedicinalherbclitoriaternateafortherapeuticapplications |