PUBLICATION
Tanshinol borneol ester (DBZ), a novel synthetic small molecule angiogenesis stimulator inspired by botanical formulations for angina pectoris
- Authors
- Liao, S., Han, L., Zheng, X., Wang, X., Zhang, P., Wu, J., Liu, R., Fu, Y., Sun, J., Kang, X., Liu, K., Fan, T., Li, S., Zheng, X.
- ID
- ZDB-PUB-190523-7
- Date
- 2019
- Source
- British journal of pharmacology 176(17): 3143-3160 (Journal)
- Registered Authors
- Wang, Xin
- Keywords
- Matrigel plug, angiogenesis, co-culture, endothelial cells, network pharmacology, zebrafish
- MeSH Terms
-
- Angina Pectoris/drug therapy*
- Angina Pectoris/metabolism
- Animals
- Camphanes/chemical synthesis
- Camphanes/chemistry
- Camphanes/pharmacology*
- Cell Movement/drug effects
- Cell Proliferation/drug effects
- Cells, Cultured
- Coculture Techniques
- Dose-Response Relationship, Drug
- Drug Compounding
- Humans
- Lactates/chemical synthesis
- Lactates/chemistry
- Lactates/pharmacology*
- Male
- Mice
- Mice, Inbred C57BL
- Mitogen-Activated Protein Kinase Kinases/metabolism
- Molecular Structure
- Neovascularization, Pathologic/drug therapy
- Neovascularization, Pathologic/metabolism
- Phosphatidylinositol 3-Kinases/metabolism
- Small Molecule Libraries/chemical synthesis
- Small Molecule Libraries/chemistry
- Small Molecule Libraries/pharmacology*
- Stereoisomerism
- Structure-Activity Relationship
- Wound Healing/drug effects
- Zebrafish
- PubMed
- 31116880 Full text @ Br. J. Pharmacol.
Citation
Liao, S., Han, L., Zheng, X., Wang, X., Zhang, P., Wu, J., Liu, R., Fu, Y., Sun, J., Kang, X., Liu, K., Fan, T., Li, S., Zheng, X. (2019) Tanshinol borneol ester (DBZ), a novel synthetic small molecule angiogenesis stimulator inspired by botanical formulations for angina pectoris. British journal of pharmacology. 176(17):3143-3160.
Abstract
Background and purpose Tanshinol borneol ester (DBZ) is a novel synthetic compound derived from Dantonic®, a botanical drug approved in 26 countries outside the USA for angina pectoris, and currently undergoing FDA Phase III clinical trial. Here, we investigated the angiogenic effects of (S)-DBZ and (R)-DBZ isomers in vitro and in vivo.
Experimental approach A network pharmacology approach was used to predict molecular targets of DBZ. The effects of DBZ isomers on proliferation, migration and tube formation of human endothelial cells were assessed. For in-vivo approaches, the transgenic Tg (vegfr2:GFP) zebrafish and C57BL/6 mouse Matrigel plug models were used. ELISA and Western blots were used to quantitate the release and expression of relevant target molecules and signaling pathways.
Key results DBZ produced a biphasic modulation on proliferation and migration of three types of human endothelial cells. Both DBZ isomers induced tube formation in Matrigel assay and a 12-day co-culture model in vitro. Moreover, DBZ promoted Matrigel neovascularization in mice, and partially reversed the vascular disruption in zebrafish induced by PTK787. Mechanistically, DBZ enhanced the cellular levels of VEGF, VEGFR2 and MMP-9, as well as activating Akt and MAPK signalling in endothelial cells. Selective inhibition of PI3K and MEK significantly attenuated its angiogenic effects.
Conclusion and implications These data revealed, for the first time, that DBZ promoted multiple key steps of angiogenesis, at least in part through Akt and MAPK signalling pathways, and suggest it may be potentially developed further for treating myocardial infarction and other cardiovascular diseases.
Errata / Notes
This article is corrected by ZDB-PUB-220906-252 . Correction: https://bpspubs.onlinelibrary.wiley.com/doi/10.1111/bph.15578 Corrects Article: https://bpspubs.onlinelibrary.wiley.com/doi/10.1111/bph.14714
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping