PUBLICATION
Notoginsenoside R1 activates the Ang2/Tie2 pathway to promote angiogenesis
- Authors
- Zhong, J., Lu, W., Zhang, J., Huang, M., Lyu, W., Ye, G., Deng, L., Chen, M., Yao, N., Li, Y., Liu, G., Liang, Y., Fu, J., Zhang, D., Ye, W.
- ID
- ZDB-PUB-200822-29
- Date
- 2020
- Source
- Phytomedicine : international journal of phytotherapy and phytopharmacology 78: 153302 (Journal)
- Registered Authors
- Keywords
- Angiogenesis, Angiopoietin-2, Notoginsenoside R1, Tie2 receptor
- MeSH Terms
-
- Angiopoietin-2/metabolism*
- Animals
- Aorta/drug effects
- Aorta/metabolism
- Axitinib/pharmacology
- Cell Movement/drug effects
- Cell Proliferation/drug effects
- Embryo, Nonmammalian/drug effects
- Ginsenosides/pharmacology*
- Human Umbilical Vein Endothelial Cells
- Humans
- Neovascularization, Physiologic/drug effects*
- Neovascularization, Physiologic/physiology
- Panax notoginseng/chemistry
- Rats, Sprague-Dawley
- Receptor, TIE-2/metabolism*
- Zebrafish/embryology
- PubMed
- 32823242 Full text @ Phytomedicine
Citation
Zhong, J., Lu, W., Zhang, J., Huang, M., Lyu, W., Ye, G., Deng, L., Chen, M., Yao, N., Li, Y., Liu, G., Liang, Y., Fu, J., Zhang, D., Ye, W. (2020) Notoginsenoside R1 activates the Ang2/Tie2 pathway to promote angiogenesis. Phytomedicine : international journal of phytotherapy and phytopharmacology. 78:153302.
Abstract
Background Therapeutic angiogenesis is a novel strategy for the treatment of ischemic diseases that involves promotion of angiogenesis in ischemic tissues via the use of proangiogenic agents. However, effective proangiogenic drugs that activate the Ang2/Tie2 signaling pathway remain scarce.
Purpose We aimed to investigate the proangiogenic activity of notoginsenoside R1 (NR1) isolated from total saponins of Panax notoginseng with regard to activation of the Ang2/Tie2 signaling pathway.
Methods We examined the proangiogenic effects of NR1 by assessing the effects of NR1 on the proliferation, migration, invasion and tube formation of human umbilical vein endothelial cells (HUVECs). The aortic ring assay and vascular endothelial growth factor receptor inhibitor (VRI)-induced vascular regression in the zebrafish model were used to confirm the proangiogenic effects of NR1 ex vivo and in vivo. Furthermore, the molecular mechanism was investigated by Western blot analysis.
Results We found that NR1 promoted the proliferation, mobility and tube formation of HUVECs in vitro. NR1 also increased the number of sprouting vessels in rat aortic rings and rescued VRI-induced vascular regression in zebrafish. NR1-induced angiogenesis was dependent on Tie2 receptor activation mediated by increased autocrine Ang2 in HUVECs, and inhibition of the Ang2/Tie2 pathway abrogated the proangiogenic effects of NR1.
Conclusions Our results suggest that NR1 promotes angiogenesis by activating the Ang2/Tie2 signaling pathway. Thus, NR1-induced activation of the Ang2/Tie2 pathway is an effective proangiogenic approach. NR1 may be useful agent for the treatment of ischemic diseases.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping