Hesperidin Inhibits Vascular Formation by Blocking the AKT/mTOR Signaling Pathways

• Published in: Preventive nutrition and food science Vol. 20; no. 4; pp. 221 - 229
• Main Author: Kim, D.K., Kyungnam University, Changwon, Republic of Korea
• Format: Journal Article
• Language: English
• Published: Korea (South) 한국식품영양과학회 01.12.2015; The Korean Society of Food Science and Nutrition
• Subjects: FLAVONOIDE; FLAVONOIDES; FLAVONOIDS; vascular formation,AKT/mTOR,HUVECs,mouse embryonic stem cells; 식품과학; AKT/mTOR; vascular formation; mouse embryonic stem cells; HUVECs; hesperidin
• ISSN: 2287-1098; 2287-8602
• DOI: 10.3746/pnf.2015.20.4.221

Hesperidin has been shown to possess a potential inhibitory effect on vascular formation in endothelial cells. However, the fundamental mechanism for the anti-angiogenic activity of hesperidin is not fully understood. In the present study, we evaluated whether hesperidin has anti-angiogenic effects in mouse embryonic stem cell (mES)-derived endothelial-like cells, and human umbilical vascular endothelial cells (HUVECs), and evaluated their mechanism via the AKT/mammalian target of rapamycin (mTOR) signaling pathway. The endothelial cells were treated with several doses of hesperidin (12.5, 25, 50, and 100 mM) for 24 h. Cell viability and vascular formation were analyzed using the 3-(4,5-dimethylthiazol- 2-yl)-2,5-diphenyltetrazolium bromide and tube formation assay, respectively. Alteration of the AKT/mTOR signaling in vascular formation was analyzed by western blot. In addition, a mouse aortic ring assay was used to determine the effect of hesperidin on vascular formation. There were no differences between the viability of mES-derived endothelial- like cells and HUVECs after hesperidin treatment. However, hesperidin significantly inhibited cell migration and tube formation of HUVECs (P¡Õ0.05) and suppressed sprouting of microvessels in the mouse aortic ring assay. Moreover, hesperidin suppressed the expression of AKT and mTOR in HUVECs. Taken together, these findings suggest that hesperidin inhibits vascular formation by blocking the AKT/mTOR signaling pathways.