Antioxidant Properties of Novel Dimers Derived from Natural β-Elemene through Inhibiting H₂O₂-Induced Apoptosis

Abstract

A series of novel β-elemene dimer derivatives were synthesized and evaluated for their antioxidant activities. The results indicated that most of the target compounds showed more potent cytoprotective effects than positive control vitamin E. In particular, dimer <b>D5</b> exhibited the strongest antioxidant activity, which was significantly superior to the active compound <b>D1</b> obtained in our previous study. Besides, <b>D5</b> did not produce obvious cytotoxicity in normal human umbilical vein endothelial cells (HUVECs) and increased the viability of HUVECs injured by H₂O₂ in a concentration-dependent manner. Further studies suggested that the cytoprotective action of <b>D5</b> might be mediated, at least in part, by increasing the intracellular superoxide dismutase activity and nitric oxide secretion as well as decreasing the intracellular malonyldialdehyde content and lactate dehydrogenase release. Furthermore, <b>D5</b> observably inhibited ROS generation and prevented H₂O₂-induced apoptosis in HUVECs possibly via inhibiting the activation of the MAPK signaling pathway.