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Aim: To investigate whether geniposide, an iridoid glucoside extracted from gardeniajasminoides ellis fruits, inhibits cell adhesion to human umbilical vein endothelial cells (HUVECs) induced by high glucose and its underlying mechanisms. Methods: HUVECs were isolated from human umbilical cords and cultured. The adhesion of monocytes to HUVECs was determined using fluorescence-labeled monocytes. The mRNA and protein levels of vascular cell adhesion molecule-1 (VCAM-1) and endothelial selectin (E-selectin) were measured using real-time RT-PCR and ELISA. Reactive oxygen species (ROS) production was measured using a fluorescent probe. The amounts of nuclear factor-kappa B (NF-KB) and inhibitory factor of NF-KB (IKB) were determined using West- ern blot analysis. The translocation of NF-KB from the cytoplasm to the nucleus was determined using immunofluorescence. Results: Geniposide (10-20 pmol/L) inhibited high glucose (33 mmol/L)-induced adhesion of monocytes to HUVECs in a dose-depen- dent manner. This compound (5-40 pmol/L) also inhibited high glucose-induced expression of VCAM-1 and E-selectin at the gene and protein levels. Furthermore, geniposide (5-20 pmol/L) decreased ROS production and prevented IKB degradation in the cytoplasm and NF-KB translocation from the cytoplasm to the nucleus in HUVECs. Conclusion: Geniposide inhibits the adhesion of monocytes to HUVECs and the expression of CAMs induced by high glucose, suggest- ing that the compound may represent a new treatment for diabetic vascular injury. The mechanism underlying this inhibitory effect may be related to the inhibition of ROS overproduction and NF-KB signaling pathway activation by geniposide.