Targeting VEGF and HIF-1α Pathways of Soy Isoflavones as Natural Modulators of Angiogenesis

Abstract

Angiogenesis, the process of new blood vessel formation, is central to both physiological homeostasis and pathological progression in cancer, cardiovascular, and inflammatory diseases. Among the key regulators, vascular endothelial growth factor (VEGF) and hypoxia-inducible factor-1α (HIF-1α) play pivotal roles in endothelial proliferation and neovascularization. Increasing evidence suggests that soy-derived isoflavones—particularly genistein and daidzein—can modulate angiogenic processes through multiple mechanisms involving VEGF and HIF-1α signaling. This review explores the molecular basis of these interactions, summarizing experimental and clinical findings on soy isoflavones as dietary modulators of angiogenesis. Emphasis is placed on their dual effects in tumor inhibition versus vascular protection, their bioavailability, and future therapeutic implications in nutraceutical and antiangiogenic strategies. Future research should aim to elucidate dose-dependent effects, bioavailability differences among isoflavone metabolites, and potential synergistic interactions with standard anti-angiogenic therapies.