Inhibitory Effect of Punicalagin on Inflammatory and Angiogenic Activation of Human Umbilical Vein Endothelial Cells

Punicalagin, a major ellagitannin isolated from pomegranate, is proved to have various pharmacological activities with an undefined therapy mechanism. The objective of this research was to demonstrate the effect of punicalagin on anti-inflammatory and angiogenic activation in human umbilical vein en...

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Autores principales: Wei Liu, Yanghui Ou, Yumeng Yang, Xuemei Zhang, Liqi Huang, Xiaohua Wang, Buling Wu, Mingcheng Huang
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Publicado: Frontiers Media S.A. 2021
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spelling oai:doaj.org-article:ed14c9e54510419fa29a08e83edfbf3d2021-11-16T07:34:21ZInhibitory Effect of Punicalagin on Inflammatory and Angiogenic Activation of Human Umbilical Vein Endothelial Cells1663-981210.3389/fphar.2021.727920https://doaj.org/article/ed14c9e54510419fa29a08e83edfbf3d2021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fphar.2021.727920/fullhttps://doaj.org/toc/1663-9812Punicalagin, a major ellagitannin isolated from pomegranate, is proved to have various pharmacological activities with an undefined therapy mechanism. The objective of this research was to demonstrate the effect of punicalagin on anti-inflammatory and angiogenic activation in human umbilical vein endothelial cells (HUVECs) and their potential mechanisms. Endothelial-leukocyte adhesion assay was applied to evaluate primary cultures of HUVECs activation following tumor necrosis factor alpha (TNF-α) treatment. The endothelial cell proliferation, migration, permeability and tube formation were assessed by EdU assay, wound migration assay, trans-endothelial electrical resistances (TEER) assay, and capillary-like tube formation assay, respectively. In addition, the expression of relevant proteins was assessed using Western blot analysis. We confirmed that punicalagin could reduce the adhesion of human monocyte cells to HUVECs in vitro and in vivo. Further, punicalagin decreased the expression of mRNA and proteins of ICAM-1 and VCAM-1 in HUVECs. Moreover, punicalagin inhibited permeability, proliferation, migration, and tube formation in VEGF-induced HUVECs, suppressed IKK-mediated activation of NF-κB signaling in TNF-α-induced endothelial cells, and inhibited vascular endothelial growth factor receptor 2 (VEGFR2) activation and downstream p-PAK1. Our findings indicated that punicalagin might have a protective effect on HUVECs activation, which suggested that punicalagin functions through an endothelial mediated mechanism for treating various disorders such as, cancer, rheumatoid arthritis, and cardiovascular disease.Wei LiuYanghui OuYumeng YangXuemei ZhangLiqi HuangXiaohua WangBuling WuBuling WuMingcheng HuangFrontiers Media S.A.articlepunicalagininflammationendothelial cellsangiogenesisNF-κBTherapeutics. PharmacologyRM1-950ENFrontiers in Pharmacology, Vol 12 (2021)
institution DOAJ
collection DOAJ
language EN
topic punicalagin
inflammation
endothelial cells
angiogenesis
NF-κB
Therapeutics. Pharmacology
RM1-950
spellingShingle punicalagin
inflammation
endothelial cells
angiogenesis
NF-κB
Therapeutics. Pharmacology
RM1-950
Wei Liu
Yanghui Ou
Yumeng Yang
Xuemei Zhang
Liqi Huang
Xiaohua Wang
Buling Wu
Buling Wu
Mingcheng Huang
Inhibitory Effect of Punicalagin on Inflammatory and Angiogenic Activation of Human Umbilical Vein Endothelial Cells
description Punicalagin, a major ellagitannin isolated from pomegranate, is proved to have various pharmacological activities with an undefined therapy mechanism. The objective of this research was to demonstrate the effect of punicalagin on anti-inflammatory and angiogenic activation in human umbilical vein endothelial cells (HUVECs) and their potential mechanisms. Endothelial-leukocyte adhesion assay was applied to evaluate primary cultures of HUVECs activation following tumor necrosis factor alpha (TNF-α) treatment. The endothelial cell proliferation, migration, permeability and tube formation were assessed by EdU assay, wound migration assay, trans-endothelial electrical resistances (TEER) assay, and capillary-like tube formation assay, respectively. In addition, the expression of relevant proteins was assessed using Western blot analysis. We confirmed that punicalagin could reduce the adhesion of human monocyte cells to HUVECs in vitro and in vivo. Further, punicalagin decreased the expression of mRNA and proteins of ICAM-1 and VCAM-1 in HUVECs. Moreover, punicalagin inhibited permeability, proliferation, migration, and tube formation in VEGF-induced HUVECs, suppressed IKK-mediated activation of NF-κB signaling in TNF-α-induced endothelial cells, and inhibited vascular endothelial growth factor receptor 2 (VEGFR2) activation and downstream p-PAK1. Our findings indicated that punicalagin might have a protective effect on HUVECs activation, which suggested that punicalagin functions through an endothelial mediated mechanism for treating various disorders such as, cancer, rheumatoid arthritis, and cardiovascular disease.
format article
author Wei Liu
Yanghui Ou
Yumeng Yang
Xuemei Zhang
Liqi Huang
Xiaohua Wang
Buling Wu
Buling Wu
Mingcheng Huang
author_facet Wei Liu
Yanghui Ou
Yumeng Yang
Xuemei Zhang
Liqi Huang
Xiaohua Wang
Buling Wu
Buling Wu
Mingcheng Huang
author_sort Wei Liu
title Inhibitory Effect of Punicalagin on Inflammatory and Angiogenic Activation of Human Umbilical Vein Endothelial Cells
title_short Inhibitory Effect of Punicalagin on Inflammatory and Angiogenic Activation of Human Umbilical Vein Endothelial Cells
title_full Inhibitory Effect of Punicalagin on Inflammatory and Angiogenic Activation of Human Umbilical Vein Endothelial Cells
title_fullStr Inhibitory Effect of Punicalagin on Inflammatory and Angiogenic Activation of Human Umbilical Vein Endothelial Cells
title_full_unstemmed Inhibitory Effect of Punicalagin on Inflammatory and Angiogenic Activation of Human Umbilical Vein Endothelial Cells
title_sort inhibitory effect of punicalagin on inflammatory and angiogenic activation of human umbilical vein endothelial cells
publisher Frontiers Media S.A.
publishDate 2021
url https://doaj.org/article/ed14c9e54510419fa29a08e83edfbf3d
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