Antiangiogenic role of natural flavonoids and their molecular mechanism: an update

Abstract
Background
Angiogenesis is the development of new blood vessels from the existing vasculature, which is important in normal developmental processes. Angiogenesis is a key step in tumor growth, invasion, and metastasis. Angiogenesis is necessary for the proper nourishment and removal of metabolic wastes from tumor sites. Therefore, modulation of angiogenesis is considered a therapeutic strategy of great importance for human health.

Main body
Numerous bioactive plant compounds are recently tested for their antiangiogenic potential. Among the most frequently studied are flavonoids which are abundantly present in fruits and vegetables. Flavonoids inhibit angiogenesis and metastasis through the regulation of multiple signaling pathways. Flavonoids regulate the expression of VEGF, matrix metalloproteinases (MMPs), EGFR, and inhibit NFB, PI3-K/Akt, and ERK1/2 signaling pathways, thereby causing strong antiangiogenic effects. This present review aimed to provide up-to-date information on the molecular mechanisms of antiangiogenic properties of natural flavonoids.

Conclusion
Presently developed antiangiogenic drugs in malignant growth treatment do not meet assumptions about adequacy and safety. So further investigations are needed in this field in the future. More recently, flavonoids are the most effective antiangiogenic agent, by inhibition of signaling pathways.