Based on previous studies showing a linear relationship between tissue monocyte content and neointimal area and Phenserine decreased neointimal thickening through blocking early monocyte recruitment by anti-inflammatory drugs, inflammatory responses related with monocyte infiltration might aggravate restenosis. In this study, EGb761 significantly and dose-dependently reduced the levels of adhesion molecules and the degree of monocyte adhesion. These findings could explain the beneficial effects of EGb761 on preventing atherosclerosis as such infiltrations of inflammatory cells promote an atherosclerotic milieu. There have been several reports showing that EGb761 improves glucose homeostasis. A recent study proved that EGb761 induced insulin secretion and that this was mediated by increased intracellular calcium transients. Another group reported that EGb761 ingestion increased plasma insulin levels in response to oral glucose loading in subjects with type 2 diabetes. These data thus suggest that EGb761 enhances pancreatic beta cell function. Consistent with these studies, the AUCglucose calculated from the IPGTT in our study was decreased slightly but significantly in EGb761-treated groups compared with controls. This improved glucose excursion might also contribute to decreased restenosis, although there is no clear explanation for the lack of a dose-dependent response. Other possible relevant factors affecting the degree of neointimal formation were also evaluated in this study. Circulating levels of adiponectin were increased significantly in EGb761 treatment in a dose-dependent manner. Adiponectin has attracted considerable attention recently as an adipokine that may have critical roles in the development of atherosclerosis. Importantly, low adiponectin level is a risk factor for the subsequent development of cardiovascular diseases. Adiponectin directly stimulates NO production from endotheliumvia activation of AMP-activated protein kinase and eNO synthase. Therefore, increasing adiponectin levels are predicted to improve both insulin sensitivity and endothelial PF 4800567 hydrochloride function by multiple mechanisms. In this study, there was a negative correlation between adiponectin and TNFa concentration, although TNFa levels were not significantly decreased by EGb761 treatment. This data suggests that reducing restenosis by EGb761 treatment may be mediated by increased adiponectin with decreased TNFa level. In addition, hsCRP, an inflammatory marker, was significantly decreased by EGb761 treatment in this study. Many types and levels of association between hsCRP and atherosclerosis or cardiovascular diseases have been suggested. The associations confirm that atherosclerosis and insulin resistance share a common inflammatory basis by demonstrating that hsCRP has direct harmful effects on vessel walls.