Properties of asiaticoside in suppressing hyperpermeability in human umbilical vein endothelial cells induced by interferon-gamma

Impairment of endothelial barrier function by vasoactive agents or inflammatory mediators promotes endothelial hyperpermeability causing the development of pathological conditions such as tissue oedema. The changes of barrier structure caused gaps formation thus promote vascular leakage of plasma fl...

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Main Author:	Khairudin, Nurnabila Huda
Format:	Thesis
Language:	English
Published:	2016
Subjects:	Endothelial Cells Interferon-gamma
Online Access:	http://psasir.upm.edu.my/id/eprint/76281/1/FPSK%28M%29%202017%2075%20IR.pdf
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spelling	my-upm-ir.762812019-11-27T07:46:15Z Properties of asiaticoside in suppressing hyperpermeability in human umbilical vein endothelial cells induced by interferon-gamma 2016-11 Khairudin, Nurnabila Huda Impairment of endothelial barrier function by vasoactive agents or inflammatory mediators promotes endothelial hyperpermeability causing the development of pathological conditions such as tissue oedema. The changes of barrier structure caused gaps formation thus promote vascular leakage of plasma fluid and macromolecules. Interferon-gamma is a well-known pro-inflammatory mediator which disturbed barrier integrity thus promotes hyperpermeability on endothelial cell. Several studies have reported that asiaticoside; a triterpenoid derived from Centella asiatica (local - pegaga) exhibits good anti-oxidant properties, wound healing, immunomodulatory, as well as anti-inflammatory effects on several inflammatory models. In order to elucidate the potential properties of asiaticoside on endothelial barrier preservation, its actions on Human Umbilical Vein Endothelial Cell (HUVEC) hyperpermeability induced by interferon-gamma was assessed. It has been found that interferon-gamma caused an increased in endothelial permeability, determined by the flux of fluorescein isothiocyanate-dextran through in vitro permeability assay. Pre-treatment of asiaticoside to interferon-gamma-activated HUVEC significantly (p < 0.05) attenuated endothelial hyperpermeability. Moreover, it was clearly demonstrated that asiaticoside helps in restoration of nitric oxide; a mediator which regulates barrier integrity and permeability regulator, back to its basal state after impairment by interferon-gamma. p38 Mitogen Activated Protein Kinase signalling pathway is believed to be involved in nitric oxide production. Thus, it was clearly clarified that p38 Mitogen Activated Protein Kinase phosphorylation, conducted via western blot analysis was deactivated after treatment with asiaticoside. For further clarification, cyclooxygenase-2 level as well as prostaglandin E2 release in interferon-gamma-activated HUVEC was also studied. Interferon-gamma has increased cyclooxygenase-2 level and prostaglandin E2 release but also stabilized by asiaticoside. These results suggest that asiaticoside regulated endothelial barrier preservation via p38 Mitogen Activated Protein Kinase phosphorylation and nitric oxide restoration. Our results suggest that asiaticoside may become an important remedy in endothelial barrier preservation induced by interferon-gamma. Endothelial Cells Interferon-gamma 2016-11 Thesis http://psasir.upm.edu.my/id/eprint/76281/ http://psasir.upm.edu.my/id/eprint/76281/1/FPSK%28M%29%202017%2075%20IR.pdf text en public masters Universiti Putra Malaysia Endothelial Cells Interferon-gamma
institution	Universiti Putra Malaysia
collection	PSAS Institutional Repository
language	English
topic	Endothelial Cells Interferon-gamma
spellingShingle	Endothelial Cells Interferon-gamma Khairudin, Nurnabila Huda Properties of asiaticoside in suppressing hyperpermeability in human umbilical vein endothelial cells induced by interferon-gamma
description	Impairment of endothelial barrier function by vasoactive agents or inflammatory mediators promotes endothelial hyperpermeability causing the development of pathological conditions such as tissue oedema. The changes of barrier structure caused gaps formation thus promote vascular leakage of plasma fluid and macromolecules. Interferon-gamma is a well-known pro-inflammatory mediator which disturbed barrier integrity thus promotes hyperpermeability on endothelial cell. Several studies have reported that asiaticoside; a triterpenoid derived from Centella asiatica (local - pegaga) exhibits good anti-oxidant properties, wound healing, immunomodulatory, as well as anti-inflammatory effects on several inflammatory models. In order to elucidate the potential properties of asiaticoside on endothelial barrier preservation, its actions on Human Umbilical Vein Endothelial Cell (HUVEC) hyperpermeability induced by interferon-gamma was assessed. It has been found that interferon-gamma caused an increased in endothelial permeability, determined by the flux of fluorescein isothiocyanate-dextran through in vitro permeability assay. Pre-treatment of asiaticoside to interferon-gamma-activated HUVEC significantly (p < 0.05) attenuated endothelial hyperpermeability. Moreover, it was clearly demonstrated that asiaticoside helps in restoration of nitric oxide; a mediator which regulates barrier integrity and permeability regulator, back to its basal state after impairment by interferon-gamma. p38 Mitogen Activated Protein Kinase signalling pathway is believed to be involved in nitric oxide production. Thus, it was clearly clarified that p38 Mitogen Activated Protein Kinase phosphorylation, conducted via western blot analysis was deactivated after treatment with asiaticoside. For further clarification, cyclooxygenase-2 level as well as prostaglandin E2 release in interferon-gamma-activated HUVEC was also studied. Interferon-gamma has increased cyclooxygenase-2 level and prostaglandin E2 release but also stabilized by asiaticoside. These results suggest that asiaticoside regulated endothelial barrier preservation via p38 Mitogen Activated Protein Kinase phosphorylation and nitric oxide restoration. Our results suggest that asiaticoside may become an important remedy in endothelial barrier preservation induced by interferon-gamma.
format	Thesis
qualification_level	Master's degree
author	Khairudin, Nurnabila Huda
author_facet	Khairudin, Nurnabila Huda
author_sort	Khairudin, Nurnabila Huda
title	Properties of asiaticoside in suppressing hyperpermeability in human umbilical vein endothelial cells induced by interferon-gamma
title_short	Properties of asiaticoside in suppressing hyperpermeability in human umbilical vein endothelial cells induced by interferon-gamma
title_full	Properties of asiaticoside in suppressing hyperpermeability in human umbilical vein endothelial cells induced by interferon-gamma
title_fullStr	Properties of asiaticoside in suppressing hyperpermeability in human umbilical vein endothelial cells induced by interferon-gamma
title_full_unstemmed	Properties of asiaticoside in suppressing hyperpermeability in human umbilical vein endothelial cells induced by interferon-gamma
title_sort	properties of asiaticoside in suppressing hyperpermeability in human umbilical vein endothelial cells induced by interferon-gamma
granting_institution	Universiti Putra Malaysia
publishDate	2016
url	http://psasir.upm.edu.my/id/eprint/76281/1/FPSK%28M%29%202017%2075%20IR.pdf
_version_	1747813147672051712

Properties of asiaticoside in suppressing hyperpermeability in human umbilical vein endothelial cells induced by interferon-gamma

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