PUBLICATION
Pro-angiogenesis effect and transcriptome profile of Shuxinyin formula in zebrafish
- Authors
- Zhou, Z.Y., Xiao, Y., Zhao, W.R., Zhang, J., Shi, W.T., Ma, Z.L., Ye, Q., Chen, X.L., Tang, N., Tang, J.Y.
- ID
- ZDB-PUB-191011-27
- Date
- 2019
- Source
- Phytomedicine : international journal of phytotherapy and phytopharmacology 65: 153083 (Journal)
- Registered Authors
- Keywords
- Angiogenesis, Coronary heart disease, Traditional Chinese medicine, Transcriptome, VEGF, Zebrafish
- MeSH Terms
-
- Angiogenesis Inducing Agents/chemistry*
- Angiogenesis Inducing Agents/pharmacology*
- Animals
- Animals, Genetically Modified
- Apoptosis/drug effects
- Autophagy/drug effects
- Drugs, Chinese Herbal/chemistry*
- Drugs, Chinese Herbal/pharmacology*
- Embryo, Nonmammalian/drug effects
- Female
- Gene Expression Profiling
- Male
- Phosphatidylinositol 3-Kinases/metabolism
- Phosphoinositide-3 Kinase Inhibitors/pharmacology
- Proto-Oncogene Proteins c-akt/antagonists & inhibitors
- Proto-Oncogene Proteins c-akt/metabolism
- Transcriptome/drug effects
- Zebrafish/embryology
- Zebrafish/genetics*
- Zebrafish/metabolism
- Zebrafish Proteins/genetics
- PubMed
- 31600690 Full text @ Phytomedicine
Citation
Zhou, Z.Y., Xiao, Y., Zhao, W.R., Zhang, J., Shi, W.T., Ma, Z.L., Ye, Q., Chen, X.L., Tang, N., Tang, J.Y. (2019) Pro-angiogenesis effect and transcriptome profile of Shuxinyin formula in zebrafish. Phytomedicine : international journal of phytotherapy and phytopharmacology. 65:153083.
Abstract
Background Angiogenesis plays a critical role in ischemia disease like coronary heart disease. Shunxinyin formula has been developed for treating coronary heart disease according to the principle of traditional Chinese medicine while its underlying mechanism is not fully elucidated.
Purpose Here, we hypothesize Shuxinyin formula could promote angiogenesis and microcirculation, and the underlying mechanism is also investigated.
Methods We established the chemical profile of Shuxinyin (SXY) extract utilizing a UHPLC-Q/Exactive analysis system and evaluated its pro-angiogenesis effect in zebrafish model. The underlying mechanisms were investigated by combination of pharmacological experiments with transcriptome analysis in zebrafish. Zebrafish treated with VEGF was served as the positive control in present study.
Results We found SXY significantly enhanced the sub-intestinal vessel plexus (SIVs) growth in zebrafish. Co-treatment and post-treatment SXY attenuated VEGF receptor tyrosine kinase inhibitor II (VRI)-induced deficiency of intersegmental vessels (ISVs) in a concentration dependent manner. Post-treatment VEGF, which is a well-known angiogenesis driver, also partially ameliorated VRI-induced ISVs deficiency. In addition, SXY inhibited the down-regulation of VEGF receptors, including kdr, flt1 and kdrl, induced by VRI in zebrafish. The pro-angiogenesis effect of SXY on VRI-induced ISVs deficiency was suppressed by PI3K and JNK inhibitors, and Akt inhibitor abolished the pro-angiogenesis effect of SXY. The transcriptome profile of SXY preventing from VRI-induced vascular growth deficiency revealed that the underlying mechanisms were also co-related to cell junction, apoptosis and autophagy.
Conclusion We could conclude that SXY presented pro-angiogenesis effect and the action mechanisms were involved in VEGF/PI3K/Akt/MAPK signaling pathways, cell junction, apoptosis and autophagy.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping