Protective Effects Of Ginkgolide B And α-zearalanol On TNFα-stimulated Endothelial Cells And The Mechanisms Involved

Excessive production of reactive oxygen species (ROS) or in unbalance with the endogenous antioxidant mechanisms may cause oxidative stress in the endothelial cells, leading to cell dysfunction, and even apoptosis or necrosis. A number of pathogenic factors associated with cardiovascular diseases, such as the tumor necrosis factor α (TNFα) and angiotensin II, are capable of stimulating the generation of ROS, and thus play an important role in the development of such diseases by activation of ROS-mediated intracellualr signaling pathway and gene expression; while the antioxidants, by reducing or abolishing the oxidative stress, have therapeutic potential for these diseases. Ginkgo biloba extract has long been used to treat the ischemic diseases such as stroke, with its pharmacological effects of scavanging free radicals and reducing lipid peroxidation of cellular membrane. However, its effect on atherosclerotic endothelial cells and the mechanisms involved are not fully elucidated, α -zearalanol (α -ZAL), a phytoestrogen, has recently been reported to be able to inhibit the formation of atherosclerotic lesion and improve the lipid profile in ovarietomized cholesterol-fed rabbits. Further evidence showed the protective effect of α -ZAL on the endothelial function stimulated by ox-LDL, but the underlying mechanisms remain largely unknown.The present study was conducted to investigate the effects of Ginkgolide B (GB) and α -ZAL on human umbilical vein endothelial cells (HUVECs ) exposed to TNFα and to explore the related mechanisms. The following aspects were studied:...