Anti-angiogenic effects of beta-eudesmol and atractylodin in developing zebrafish embryos

Angiogenesis is the process of formation of new blood vessels which plays an essential role in the normal physiological development of the organs and systems. Several factors contribute to and regulate this process. Unregulated angiogenesis, however, is harmful and is usually found in tumors and cancerous cells. beta-Eudesmol and atractylodin are sesquiterpenoid contents extracted from the rhizome of Atractylodes lancea (AL). Reports suggest potential anti-angiogenic activities of both compounds. In this study, the anti-angiogenic activities of both compounds were investigated using the well-established zebrafish in vivo model. Zebrafish embryos were treated with a series of concentrations (6.3, 12.5, 25, and 50 mu M) of beta-eudesmol and (6.3, 12.5, and 25 mu M) of atractylodin up to 72 h post-fertilization. Assessment of the effects on phenotypic blood vessel development (sub intestinal vessel intersection count) revealed that both the compounds inhibited vessel development, particularly at higher concentrations. At the genetic levels, only beta-eudesmol significantly downregulated the expression of the Vegfaa gene and also its receptor Vegfr2. beta-Eudesmol also affected the expression of Vegfaa protein in a concentration-dependent manner. Results indicate that beta-eudesmol exerts anti-angiogenic property through inhibition of Vegfaa at both the gene and protein levels. However, atractylodin does not possess this property.