Mangiferin enhances human umbilical vein relaxation associated with no signaling, without exhibiting cytotoxicity on human endothelial cells

Abstract

Mangiferin, a xanthone isolated from mango, has been shown to effectively induce vasodilation in the rat mesenteric artery without exhibiting toxicity on rat vascular smooth muscle cells (VSMCs). The mechanism of mangiferin was demonstrated through the upregulation of endothelial nitric oxide synthase (eNOS) expression and enhancement of nitric oxide (NO) production in rats. However, the effect of mangiferin on human blood vessels has not been clarified. We aimed to investigate whether mangiferin induces vasodilation in human umbilical vein (HUV) and its toxicity on human umbilical vein endothelial cells (HUVECs). A mangiferin-induced HUV relaxation was measured by using organ bath technique. The cytotoxicity of mangiferin-treated HUVECs were tested using cell viability assay. Mangiferin effectively induced vasodilation in 5-HT-induced HUV contractions, with an EC50 of approximately 2 µM and a maximum effect of around 30%. This vasodilatory response was partially mediated through a NO-dependent pathway, as evidenced by its inhibition by eNOS inhibitors. Furthermore, prolonged exposure to mangiferin (72 hours) in HUVECs showed no cytotoxic effects, underscoring its potential as a safe and effective vasodilating agent for vascular health applications.