ORIGINAL RESEARCH article
Front. Chem.
Sec. Medicinal and Pharmaceutical Chemistry
This article is part of the Research TopicBioactive Natural Products for Health: Isolation, Structural Elucidation, Biological Evaluation, Structure-activity Relationship, and Mechanism - Volume IIView all 8 articles
Insights into the pro-angiogenic effect of hydroxysafflor yellow A (HSYA): targeting HIF-1α and MMP9 in HMEC-1
Provisionally accepted
- 1College of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, Fuzhou, China
- 2Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, China
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Background: Angiogenesis is a fundamental physiological process mediating vascular network formation, represents a critical therapeutic target for ischemic diseases and tumor neovascularization. Xuefu Zhuyu decoction (XFZYD), a classical formula for promoting blood circulation and resolving stasis, demonstrates pro-angiogenic effect with safflower functioning as the sovereign herb. Hydroxysafflor yellow A (HSYA), the primary bioactive constituent of safflower, exerts potent angiogenesis modulation, defining its pharmacological significance. Methods: In this study, in vitro tubulogenesis assay and cytocompatibility analysis were employ on human microvascular endothelial cell (HMEC-1), followed by target prediction via network pharmacology and molecular docking; immunoblotting analysis was performed to experimentally validate the pro-angiogenic molecular mechanism of HSYA. Results: HSYA exerted concentration-dependent pro-angiogenic effects on HMEC-1 cells over 24 hours without compromising cell viability (p>0.05) across 0 to 200 μM. 121 potential targets of HSYA within the angiogenesis regulatory network were identified. Functional enrichment analysis revealed fluid shear stress, lipid metabolism, HIF-1, PI3K-Akt, and VEGF signal pathways as primary regulatory pathways. 8 hub targets derived from the protein-protein interaction (PPI) network were subjected to molecular docking. High-affinity interactions were observed for key angiogenesis regulators: MMP9 (−7.6 kcal·mol⁻¹), and HIF-1α(−4.5 kcal·mol⁻¹), which were functionally validated by immunoblotting analysis, preliminary demonstrating the mechanism of HSYA-mediated angiogenesis promotion. Conclusion: HSYA demonstrates significant pro-angiogenic activity on HMEC-1. Mechanistically, HSYA modulates multiple signaling pathways, with HIF-lα and MMP9 demonstrating regulatory significance. These findings suggest a molecular basis for HSYA's therapeutic potential in ischemic vascular pathologies.
Keywords: Angiogenesis, HIF-1α, HSYA, MMP9, Network Pharmacology
Received: 26 Sep 2025; Accepted: 17 Dec 2025.
Copyright: © 2025 Fu, Dong, Yao, Yu, Wang, Wang and Lin. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
He Wang
Fan Lin
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