Mangiferin inhibits high-fat diet induced vascular injury via regulation of PTEN/AKT/eNOS pathway

Mangiferin (MAN), a naturally occurring polyphenol commonly found in mango and papaya. However, little is known its anti-vascular injury effects and the underlying mechanisms. This paper investigated the anti-vascular injury effect of MAN and the mechanisms in high-fat diet (HFD)-induced C57BL/6J mice and oxidized low-density lipoprotein (ox-LDL) induced human umbilical vein endothelial cells (HUVECs). The levels of plasma lipid, inflammatory factors and nitric oxide (NO) in mice were evaluated. The expression levels of PI3K, AKT, eNOS, PTEN and their phosphorylated proteins were measured by western blots. In addition, the PTEN-siRNA HUVECs were also used. The result showed that MAN markedly decreased the plasma lipid, inflammatory level in HFD-induced vascular injury mice respectively. Furthermore, MAN alleviate ox-LDL-stimulated dysfunction of HUVECs, restored the diminished NO release, decreased the ROS generation, significantly increased the expression of p-Akt, p-eNOS, and decreased the expression of PTEN, but have no effect on PI3K. However, the protective effects of MAN were significantly reduced by co-treatment with PI3K inhibitor or abolished by eNOS inhibitor. In addition, MAN has no protective effect on ox-LDL induced PTEN-siRNA HUVECs injury. Collectively, MAN appeared to alleviate ox-LDL-stimulated dysfunction of HUVECs via the PTEN/Akt/eNOS signaling pathway, thus decrease vascular injury in HFD-administrated mice. (c) 2018 The Authors. Production and hosting by Elsevier B.V. on behalf of Japanese Pharmacological Society.