PUBLICATION
A Research Article Submitted to Journal of Ethnopharmacology Naoxintong restores Ischemia Injury and inhibits Thrombosis via COX2-VEGF/ NFκB Signaling
- Authors
- Wang, Z., Liu, P., Hu, M., Lu, S., Lyu, Z., Kou, Y., Sun, Y., Zhao, X., Liu, F., Tian, J.
- ID
- ZDB-PUB-210115-7
- Date
- 2021
- Source
- Journal of ethnopharmacology 270: 113809 (Journal)
- Registered Authors
- Tian, Jing
- Keywords
- COX2, Cardiovascular diseases (CVD), Hypoxic-ischemia (HI), NFκB, Naoxintong (NXT), Oxygen-Glucose Deprivation-Reoxygenation (OGD/R), VEGF, Zebrafish thrombosis model
- MeSH Terms
-
- Animals
- Apoptosis/drug effects
- Cell Line
- Cell Survival/drug effects
- Cyclooxygenase 2/metabolism*
- Cyclooxygenase Inhibitors/pharmacology
- Cyclooxygenase Inhibitors/therapeutic use
- Disease Models, Animal
- Drugs, Chinese Herbal/pharmacology*
- Gene Expression Profiling
- Gene Expression Regulation/drug effects
- Human Umbilical Vein Endothelial Cells/drug effects
- Human Umbilical Vein Endothelial Cells/metabolism
- Humans
- NF-kappa B/metabolism*
- Nitrobenzenes/pharmacology
- Nitrobenzenes/therapeutic use
- Protein Interaction Maps/drug effects
- Reperfusion Injury/metabolism
- Reperfusion Injury/prevention & control*
- Signal Transduction/drug effects*
- Sulfonamides/pharmacology
- Sulfonamides/therapeutic use
- Thrombosis/metabolism
- Thrombosis/prevention & control*
- Vascular Endothelial Growth Factors/metabolism*
- Zebrafish
- PubMed
- 33444716 Full text @ J. Ethnopharmacol.
Citation
Wang, Z., Liu, P., Hu, M., Lu, S., Lyu, Z., Kou, Y., Sun, Y., Zhao, X., Liu, F., Tian, J. (2021) A Research Article Submitted to Journal of Ethnopharmacology Naoxintong restores Ischemia Injury and inhibits Thrombosis via COX2-VEGF/ NFκB Signaling. Journal of ethnopharmacology. 270:113809.
Abstract
Ethnopharmacological relevance Naoxintong (NXT) is a traditional Chinese medicine preparation that is often used in combination with aspirin in the treatment of cardiovascular diseases (CVD). One of the main symptoms of CVD is hypoxic-ischemia (HI). The purpose of this study is to find out the molecular nodes targeted by NXT and its related molecular pathways in vascular repair.
Materials and methods First, human vein umbilical endothelial cells (EA.hy926) were utilized to set up the Oxygen-Glucose Deprivation-Reoxygenation (OGD/R) model and treated with NXT. Cell proliferation, damage and apoptosis were detected by MTT, LDH, and flow cytometry assays. Second, transcriptional responses of OGD/R cells to NXT treatment were investigated. qRT-PCR, western blotting and inhibitor assays were performed. Third, the anti-thrombotic effect of NXT was evaluated by the zebrafish thrombosis model. Morphological observation, histological staining and qRT-PCR assays were implemented on zebrafish model to further observe in vivo the therapeutic effects of NXT on ischemia and thrombosis.
Results In OGD/R EA.hy926 cells, NXT treatment could reduce ischemic vascular injury, increase cell viability and decrease the proportion of apoptosis. Through RNA-seq analysis, 183 differentially expressed genes (DEGs) were screened with 110 up-regulated genes and 73 down-regulated genes between OGD/R and OGD/R+NXT treated EA.hy926 cells. VEGF and NFκB pathways were enriched. Among these genes, COX2 was identified as one of important targets via which NXT could restore vascular injury. COX2 inhibitor (NS-398), and aspirin, a drug that prevents the development of CVD by targeting COX2, exhibited similar effects to NXT in the treatment of OGD/R EA.hy926 cells. In zebrafish thrombosis model, NXT could attenuate tail venous thrombus and recover the quantity of heart red blood cells. Furthermore, NXT could prevent the formulation of thrombosis and eliminate inflammation in zebrafish by COX2-VEGF/NFκB signaling.
Conclusion Our studies implicated that NXT could restore HI injury and inhibit thrombosis through COX2-VEGF/NFκB signaling, which is consistent with the molecular target of aspirin. This finding might explain the principle of NXT combined with aspirin in the treatment of cardiovascular diseases.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping