The Aesculus genus has several species, most notably Aesculus hippocastanum , with reported cytotoxic and venotonic effects. The angiogenic effect from A. hippocastanum is of interest given the current limitations of anti-angiogenic therapeutics. Aesculus glabra (Willdenow), known as the Ohio Buckeye Tree is a species native to North America with reported medicinal use by the Native Americans. Previous phytochemical studies have focused on the seed and leaf contents of the glabra species, with most of them reporting cytotoxic activity. In this study, we assessed preliminary anti-angiogenic activity and toxicity of isolated compounds from the bark of A. glabra utilizing a zebrafish ( Danio rerio ) model. Procyanidin A2 and epicatechin, two pure isolates, were tested using zebrafish and gave an anti-angiogenic response, suggesting an underlying mechanism involved in vascular development. • The traditional use and therapeutic properties of the Aesculus genus are highlighted. • Aesculus glabra has been an understudied species in the Aesculus genus. • Research on A. glabra has not previously been focused on the bark. • Angiogenesis assessment of A. glabra isolates validate its therapeutic potential.