Posidonia oceanica Extract Inhibits Vegf-Induced Angiogenic and Oxidative Responses in Human Endothelial Colony-Forming Cells

Angiogenesis, the formation of new blood vessels from pre-existing vasculature, is essen-tial for physiological processes such as development and wound healing, but its dysregu-lation contributes to a range of pathological conditions including cancer, diabetic reti-nopathy, and chronic inflammation. In recent years, marine-derived compounds have emerged as promising multi-target agents with anti-angiogenic potential. Posidonia ocean-ica, a Mediterranean seagrass traditionally used in folk medicine, is increasingly recog-nized for its pharmacological properties, including antioxidant, anti-inflammatory, and anti-invasive activities. This study investigated the effects of an hydroalcoholic extract from P. oceanica leaves (POE) on human Endothelial Colony-Forming Cells (ECFCs), a subpopulation of endothelial progenitor cells with high proliferative and vessel-forming capacity, and a relevant model for studying pathological angiogenesis. ECFCs were treat-ed with POE (4–8 µg/ml), and cell viability, morphology, migration, invasion, tube for-mation, oxidative stress, and activation markers were evaluated. POE did not alter ECFC morphology or viability, as confirmed by Trypan Blue and MTT assays. However, func-tional assays revealed that POE significantly impaired ECFC migration, invasion, and in vitro angiogenesis in a dose-dependent manner. Under VEGF stimulation, POE reduced intracellular ROS accumulation and downregulated key redox-regulating genes (HTRX1, HTRX2, PRDX2, AKR1C1, AKR1B10). Western blot analysis showed that POE inhibited VEGF-induced phosphorylation of KDR, mTOR and p-ERK, while p-AKT remained ele-vated, indicating selective disruption of VEGF downstream signaling. Furthermore, POE reduced the expression of pro-inflammatory and pro-coagulant markers (VCAM-1, ICAM-1, TF) and partially reversed TNF-α–induced endothelial activation. These findings suggest that POE exerts anti-angiogenic effects through a multitargeted mechanism, sup-porting its potential as a natural therapeutic agent for diseases characterized by aberrant angiogenesis.