Differential angiogenic activities of naringin and naringenin in zebrafish in vivo and human umbilical vein endothelial cells in vitro

Naringin, a flavanone glycoside, and naringenin, the aglycone of naringin, are commonly found in the pericarp of citrus fruits and have also been considered as potential bioactive flavanones. In the present study, treatment with naringenin showed an inhibitory effect on SIV formation in zebrafish embryos, which demonstrates its potential anti-angiogenic activity. In a chemically-induced blood vessel loss model in zebrafish, we found that naringin exhibited remarkably pro-angiogenesis activity on the restoration of blood vessel loss, and significantly reversed VRI-induced down-regulation of flt1 mRNA expression. In an in vitro study of cultured human umbilical vein endothelial cells (HUVEC), our results showed that naringin specifically promoted HUVEC migration but not proliferation. Taken together, these results suggest that naringin and naringenin have differential angiogenesis activities where naringin, as a novel angiogenic agent, has the potential to be developed as a therapeutic agent for diseases associated with insufficient angiogenesis, such as ischemia heart disease.