PUBLICATION
Cardenolide-rich fraction of Pergularia tomentosa as a novel Antiangiogenic agent mainly targeting endothelial cell migration
- Authors
- Hosseini, M., Ayyari, M., Meyfour, A., Piacente, S., Cerulli, A., Crawford, A., Pahlavan, S.
- ID
- ZDB-PUB-200702-9
- Date
- 2020
- Source
- Daru : journal of Faculty of Pharmacy, Tehran University of Medical Sciences 28(2): 533-543 (Journal)
- Registered Authors
- Ayyari, Mahdi
- Keywords
- Antiangiogenesis, Asclepiadaceae, Cardenolide, Pergularia tomentosa, VE-cadherin, Zebrafish
- MeSH Terms
-
- Angiogenesis Inhibitors/chemistry
- Angiogenesis Inhibitors/isolation & purification
- Angiogenesis Inhibitors/pharmacology*
- Animals
- Animals, Genetically Modified
- Cadherins/metabolism
- Cardenolides/chemistry
- Cardenolides/isolation & purification
- Cardenolides/pharmacology*
- Cell Movement/drug effects
- Chickens
- Chorioallantoic Membrane/blood supply
- Chorioallantoic Membrane/drug effects
- Embryo, Nonmammalian/blood supply
- Embryo, Nonmammalian/drug effects*
- Green Fluorescent Proteins/genetics
- Green Fluorescent Proteins/metabolism
- Human Umbilical Vein Endothelial Cells
- Humans
- Magnoliopsida/chemistry*
- Metabolomics/methods
- Plant Components, Aerial/chemistry
- Plant Roots/chemistry
- Zebrafish
- PubMed
- 32607956 Full text @ Daru
Citation
Hosseini, M., Ayyari, M., Meyfour, A., Piacente, S., Cerulli, A., Crawford, A., Pahlavan, S. (2020) Cardenolide-rich fraction of Pergularia tomentosa as a novel Antiangiogenic agent mainly targeting endothelial cell migration. Daru : journal of Faculty of Pharmacy, Tehran University of Medical Sciences. 28(2):533-543.
Abstract
Purpose Angiogenesis related abnormalities underlie several life-threatening disorders. Despite approved therapies, scientists have yet to develop highly efficient, low cost approaches with minimal side effects.
Methods We evaluated the antiangiogenic activity of 50% hydroalcoholic extracts of Pergularia tomentosa L. root and aerial parts along with their EtOAc and water fractions, in vivo and in vitro. Transgenic zebrafish line Tg(fli1:EGFP) was used for in vivo assay and human umbilical vein endothelial cell (HUVEC) migration test along with possibility of tube formation were performed as in vitro tests. Furthermore, microvasculature in chicken chorioallantoic membrane (CAM) was assessed under P. tomentosa treatment. The fractionation of the 50% hydroalcoholic extracts was led to the identification of the best active fraction in this study. The metabolite profiling of the active fraction was also carried out using LC-HRESIMS analysis.
Results Pergularia tomentosa markedly inhibited intersegmental vessel (ISV) formation at 48 h post-fertilization (hpf) embryos in zebrafish. The water fraction of root hydroalcoholic extract (PtR2), showed strong antiangiogenic effect with minimal adverse viability impacts. Over 80% of embryos showed more than 50% inhibition in their ISV development at 20 and 40 μg/mL. PtR2 at 20 μg/mL substantially reduced human umbilical vein endothelial cell (HUVEC) migration up to 40%, considerable destruction of the formed tubes in the tube formation and microvasculature in CAM assays. Immunocytochemistry showed a marked reduction in vascular endothelial cadherin (VE-cadherin) abundance at cell junctions concurrent with substantial reduction of phospho-Akt (p-Akt) and β-catenin protein expressions. Phytochemical profile of PtR2 showed a rich source of cardenolide structures, including ghalakinoside, calactin and calotropin derivatives.
Conclusion Thus, the P. tomentosa cardenolide-rich fraction (PtR2) may hold a considerable promise for an antiangiogenic impact by impairment of endothelial cell (EC) migration and viability. Graphical abstract.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping