Effects of hesperetin on vessel structure formation in mouse embryonic stem (mES) cells

Objective The present study investigated the effects of hesperetin on vessel structure formation in mouse embryonic stem (mES) cells with regard to whether hesperetin acts as an antioxidant or pro-oxidant. Some flavonoids enhance antioxidant systems while increasing oxidative stress in the body. Methods After their differentiation into endothelial-like cells for 10 d, mES cells were treated with 1 to 100 μM of hesperetin for 24 h. Results Hesperetin efficiently inhibited the formation of vessel-like tubular structures consisting of platelet-endothelial cell adhesion molecule-1–immunoreactive cells and significantly (P < 0.05) increased the generation of reactive oxygen species in a concentration-dependent manner. Although glutathione (in its reduced and oxidized forms) in mES cells was not affected by hesperetin, the 8-iso-prostaglandin F2α content was decreased. In addition, cytotoxicity-induced hesperetin was not found; lactate dehydrogenase release and cell viability were determined as an index of cell damage. Conclusion Taken together, the present study shows that hesperetin inhibits vessel formation by pro-oxidant means and suggests its potential as an antiangiogenic agent.