PRO AND ANTIANGIOGENIC PROPERTIES OF VITIS VINIFERA BIOACTIVES: A SYSTEMATIC REVIEW OF EXTRACTS, MECHANISMS, AND THERAPEUTIC POTENTIAL

Vitis vinifera is recognized for its diverse phytochemical composition, particularly polyphenols, which exert context‑specific modulatory effects on angiogenesis. This review explores how different extraction solvents aqueous, alcoholic, benzene, and acetone impact the biological activity of grape-derived compounds using the chick chorioallantoic membrane (CAM) assay as an experimental platform. The choice of solvent was found to be a critical determinant of both chemical stability and biological response. Water and alcohol-based extracts generally favoured neovascularization, whereas benzene and acetone extracts produced inhibitory effects, indicating possible therapeutic applications in tissue regeneration and cancer, respectively. Mechanistic insights suggest these differential effects are mediated through oxidative stress regulation and angiogenic signaling, with changes observed in lipid peroxidation (LPO), glutathione (GSH), vascular endothelial growth factor (VEGF), and alkaline phosphatase (ALP). These molecular alterations parallel functional outcomes in endothelial proliferation, migration, and vessel organization within the CAM model. Despite promising findings, lack of standardized extraction protocols, limited reproducibility, and challenges related to bioavailability restrict clinical translation. Novel approaches, including nanotechnology-based delivery systems and integrative omics, may enhance consistency and therapeutic applicability. Overall, Vitis vinifera extracts display both pro- and anti-angiogenic properties depending on solvent systems, and the CAM model remains a valuable preclinical tool for screening. Further multidisciplinary research is essential to establish standardized methodologies and facilitate translational advancement.