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Updated: Jul 30, 2025
In Vivo Imaging and Quantitation of the Host Angiogenic Response in Zebrafish Tumor Xenografts
Published on: August 14, 2019
Xinkeshu tablets promote angiogenesis in zebrafish embryos and human umbilical vein endothelial cells through
Qing Liu1, Huazheng Zhang2, Ying An1
1Biology Institute, Qilu University of Technology (Shandong Academy of Sciences), Jinan, 250103, China; School of Pharmacology, Shandong University of Traditional Chinese Medicine, Jinan, 250355, China.
Ethnopharmacological Relevance:
Angiogenesis is particularly important in ischemic cardiovascular diseases such as coronary heart disease (CHD). Xinkeshu tablets (XKS) are a commonly used Chinese patent medicine for CHD with a defined clinical effect. However, the proangiogenic effect of XKS remains unknown.
Aim Of The Study:
We attempted to investigate the chemical composition and proangiogenic effect of XKS, as well as its underlying mechanisms.
Materials And Methods:
The chemical composition of a XKS methanol extract was analyzed using a UPLC-Q-Orbitrap-MS system. The compound's proangiogenic effects were evaluated in zebrafish embryos and human umbilical vein endothelial cells (HUVECs). Furthermore, the underlying mechanisms were investigated using transcriptome assays and real-time quantitative PCR validation.
Results:
We identified 116 chemical constituents of XKS. XKS significantly stimulated subintestinal vessel plexus (SIVs) growth and rescued tyrosine kinase inhibitor (PTK787)-induced intersegmental vessels (ISVs) injury in zebrafish in a concentration-dependent manner. XKS significantly rescued the proliferation, migration capacity and tube formation of Recombinant VEGFR tyrosine kinase inhibitor II (VRI)-injured HUVECs. XKS promoted angiogenesis through multiple signaling pathways, including metabolic pathways, the PPAR signaling pathway, the AGE-RAGE signaling pathway, the NOD-like receptor signaling pathway, the VEGF signaling pathway, and the PI3K/Akt signaling pathway.
Conclusion:
Herein, we identified 116 chemical constituents of XKS for the first time and demonstrated that XKS may regulate angiogenesis through multiple signaling pathways to treat CHD.
