Traditional Chinese medicine targets vascular endothelial growth factor receptor 2 to treat retinal...

Retinal neovascularization (RNV) underlies the major vision-threatening complications of ischemic retinal diseases, leading to progressive and often irreversible visual impairment. Current laser and drug interventions for RNV are constrained by prohibitive costs and adverse effects, driving the urgent demand for lesion-specific targeted therapeutics. Traditional Chinese medicine (TCM) is a high-quality source of drugs with novel structures, unique activities, and high biocompatibility. This review systematically evaluates the inhibitory effects of bioactive molecules derived from TCM on pathological vascular proliferation and vascular endothelial growth factor receptor 2 (VEGFR2) signaling. We performed structure‒activity analyses of the interactions of polyphenols, flavonoids, alkaloids, terpenoids, quinones and other natural products with VEGFR2 on the basis of scaffold structure to summarize the dominant scaffolds and optimization strategies. This review highlights the structural diversity and multifaceted bioactivities of naturally occurring VEGFR2 inhibitors, with a focus on their translational potential for treating RNV diseases, providing a blueprint for discovering high-efficacy natural therapeutics and enabling structure-informed optimization of existing agents.