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Combination of Ginsenosides Rb2 and Rg3 Promotes Angiogenic Phenotype of Human Endothelial Cells via PI3K/Akt and MAPK/ERK Pathways

Shexiang Baoxin Pill (SBP) is an oral formulation of Chinese materia medica for the treatment of angina pectoris. It displays pleiotropic roles in protecting the cardiovascular system. However, the mode of action of SBP in promoting angiogenesis, and in particular the synergy between its constituent...

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Autores principales: Choi, Ran Joo, Mohamad Zobir, Siti Zuraidah, Alexander-Dann, Ben, Sharma, Nitin, Ma, Marcella K.L., Lam, Brian Y.H., Yeo, Giles S.H., Zhang, Weidong, Fan, Tai-Ping, Bender, Andreas
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7902932/
https://www.ncbi.nlm.nih.gov/pubmed/33643049
http://dx.doi.org/10.3389/fphar.2021.618773
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author Choi, Ran Joo
Mohamad Zobir, Siti Zuraidah
Alexander-Dann, Ben
Sharma, Nitin
Ma, Marcella K.L.
Lam, Brian Y.H.
Yeo, Giles S.H.
Zhang, Weidong
Fan, Tai-Ping
Bender, Andreas
author_facet Choi, Ran Joo
Mohamad Zobir, Siti Zuraidah
Alexander-Dann, Ben
Sharma, Nitin
Ma, Marcella K.L.
Lam, Brian Y.H.
Yeo, Giles S.H.
Zhang, Weidong
Fan, Tai-Ping
Bender, Andreas
author_sort Choi, Ran Joo
collection PubMed
description Shexiang Baoxin Pill (SBP) is an oral formulation of Chinese materia medica for the treatment of angina pectoris. It displays pleiotropic roles in protecting the cardiovascular system. However, the mode of action of SBP in promoting angiogenesis, and in particular the synergy between its constituents is currently not fully understood. The combination of ginsenosides Rb2 and Rg3 were studied in human umbilical vein endothelial cells (HUVECs) for their proangiogenic effects. To understand the mode of action of the combination in more mechanistic detail, RNA-Seq analysis was conducted, and differentially expressed genes (DEGs), pathway analysis and Weighted Gene Correlation Network Analysis (WGCNA) were applied to further identify important genes that a play pivotal role in the combination treatment. The effects of pathway-specific inhibitors were observed to provide further support for the hypothesized mode of action of the combination. Ginsenosides Rb2 and Rg3 synergistically promoted HUVEC proliferation and tube formation under defined culture conditions. Also, the combination of Rb2/Rg3 rescued cells from homocysteine-induced damage. mRNA expression of CXCL8, CYR61, FGF16 and FGFRL1 was significantly elevated by the Rb2/Rg3 treatment, and representative signaling pathways induced by these genes were found. The increase of protein levels of phosphorylated-Akt and ERK42/44 by the Rb2/Rg3 combination supports the notion that it promotes endothelial cell proliferation via the PI3K/Akt and MAPK/ERK signaling pathways. The present study provides the hypothesis that SBP, via ginsenosides Rb2 and Rg3, involves the CXCR1/2 CXCL8 (IL8)-mediated PI3K/Akt and MAPK/ERK signaling pathways in achieving its proangiogenic effects.
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spelling pubmed-79029322021-02-25 Combination of Ginsenosides Rb2 and Rg3 Promotes Angiogenic Phenotype of Human Endothelial Cells via PI3K/Akt and MAPK/ERK Pathways Choi, Ran Joo Mohamad Zobir, Siti Zuraidah Alexander-Dann, Ben Sharma, Nitin Ma, Marcella K.L. Lam, Brian Y.H. Yeo, Giles S.H. Zhang, Weidong Fan, Tai-Ping Bender, Andreas Front Pharmacol Pharmacology Shexiang Baoxin Pill (SBP) is an oral formulation of Chinese materia medica for the treatment of angina pectoris. It displays pleiotropic roles in protecting the cardiovascular system. However, the mode of action of SBP in promoting angiogenesis, and in particular the synergy between its constituents is currently not fully understood. The combination of ginsenosides Rb2 and Rg3 were studied in human umbilical vein endothelial cells (HUVECs) for their proangiogenic effects. To understand the mode of action of the combination in more mechanistic detail, RNA-Seq analysis was conducted, and differentially expressed genes (DEGs), pathway analysis and Weighted Gene Correlation Network Analysis (WGCNA) were applied to further identify important genes that a play pivotal role in the combination treatment. The effects of pathway-specific inhibitors were observed to provide further support for the hypothesized mode of action of the combination. Ginsenosides Rb2 and Rg3 synergistically promoted HUVEC proliferation and tube formation under defined culture conditions. Also, the combination of Rb2/Rg3 rescued cells from homocysteine-induced damage. mRNA expression of CXCL8, CYR61, FGF16 and FGFRL1 was significantly elevated by the Rb2/Rg3 treatment, and representative signaling pathways induced by these genes were found. The increase of protein levels of phosphorylated-Akt and ERK42/44 by the Rb2/Rg3 combination supports the notion that it promotes endothelial cell proliferation via the PI3K/Akt and MAPK/ERK signaling pathways. The present study provides the hypothesis that SBP, via ginsenosides Rb2 and Rg3, involves the CXCR1/2 CXCL8 (IL8)-mediated PI3K/Akt and MAPK/ERK signaling pathways in achieving its proangiogenic effects. Frontiers Media S.A. 2021-02-10 /pmc/articles/PMC7902932/ /pubmed/33643049 http://dx.doi.org/10.3389/fphar.2021.618773 Text en Copyright © 2021 Choi, Mohamad Zobir, Alexander-Dann, Sharma, Ma, Lam, Yeo, Zhang, Fan and Bender. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Choi, Ran Joo
Mohamad Zobir, Siti Zuraidah
Alexander-Dann, Ben
Sharma, Nitin
Ma, Marcella K.L.
Lam, Brian Y.H.
Yeo, Giles S.H.
Zhang, Weidong
Fan, Tai-Ping
Bender, Andreas
Combination of Ginsenosides Rb2 and Rg3 Promotes Angiogenic Phenotype of Human Endothelial Cells via PI3K/Akt and MAPK/ERK Pathways
title Combination of Ginsenosides Rb2 and Rg3 Promotes Angiogenic Phenotype of Human Endothelial Cells via PI3K/Akt and MAPK/ERK Pathways
title_full Combination of Ginsenosides Rb2 and Rg3 Promotes Angiogenic Phenotype of Human Endothelial Cells via PI3K/Akt and MAPK/ERK Pathways
title_fullStr Combination of Ginsenosides Rb2 and Rg3 Promotes Angiogenic Phenotype of Human Endothelial Cells via PI3K/Akt and MAPK/ERK Pathways
title_full_unstemmed Combination of Ginsenosides Rb2 and Rg3 Promotes Angiogenic Phenotype of Human Endothelial Cells via PI3K/Akt and MAPK/ERK Pathways
title_short Combination of Ginsenosides Rb2 and Rg3 Promotes Angiogenic Phenotype of Human Endothelial Cells via PI3K/Akt and MAPK/ERK Pathways
title_sort combination of ginsenosides rb2 and rg3 promotes angiogenic phenotype of human endothelial cells via pi3k/akt and mapk/erk pathways
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7902932/
https://www.ncbi.nlm.nih.gov/pubmed/33643049
http://dx.doi.org/10.3389/fphar.2021.618773
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