Targeting vascular endothelial growth factor (VEGF)-induced angiogenesis with Rosa hybrida leaf extract via VEGF receptor-2 signaling and matrix metalloproteinase-2 inhibition.

BACKGROUND/

OBJECTIVES

Angiogenesis is essential for tumor growth, tissue repair, and cell development. Rosa hybrida is a widely cultivated ornamental plant, and research on its petals has been conducted. However, despite the presence of flavonoids and terpenoids in the leaves, the biological activity of rose leaves remains unclear. This study investigated the anti-angiogenic potential of R. hybrida leaf extract (RLE) using a vascular endothelial growth factor (VEGF)-stimulated angiogenic model.

MATERIALS/

METHODS

RLE was prepared, chemically profiled by high-performance liquid chromatography, and used in both in vitro and ex vivo assays. Human umbilical vein endothelial cells (HUVECs) were treated with RLE in the presence of VEGF. Assays for endothelial cell proliferation, tube formation, migration, invasion, and angiogenic signaling protein (VEGFR-2, protein kinase B [AKT], extracellular signal-regulated kinase [ERK], and endothelial nitric oxide synthase [eNOS]) phosphorylation were conducted. Molecular docking was performed to predict interactions between major RLE compounds and VEGFR-2. Matrix metalloproteinase-2 (MMP-2) level was also evaluated by immunoblot and gelatin zymography. The mouse aortic ring assay was used to assess microvessel sprouting.

RESULTS

RLE inhibited VEGF-induced proliferation, tube formation, migration, and invasion in HUVECs. RLE treatment also reduced the phosphorylation of VEGFR-2 and downstream signaling molecules, including AKT, ERK, and eNOS. Molecular docking supported the potential interaction between major RLE compounds and VEGFR-2. Additionally, RLE inhibited MMP-2-mediated extracellular matrix remodeling and attenuated VEGF-stimulated microvessel sprouting in the aortic ring assay.

CONCLUSION

RLE exerts potent anti-angiogenic effects by modulating the VEGF/VEGFR-2 signaling cascade and inhibiting MMP-2 activity. As a previously underutilized botanical resource, RLE may serve as a promising complementary therapeutic agent for diseases related to angiogenesis.