Geniposide inhibits high glucose-induced cell adhesion through the NF-κB signaling pathway in human umbilical vein endothelial cells

Abstract

Aim: To investigate whether geniposide, an iridoid glucoside extracted from gardenia jasminoides 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-κB) and inhibitory factor of NF-κB (IκB) were determined using Western blot analysis. The translocation of NF-κB from the cytoplasm to the nucleus was determined using immunofluorescence. Results: Geniposide (10-20 µmol/L) inhibited high glucose (33 mmol/L)-induced adhesion of monocytes to HUVECs in a dose-dependent manner. This compound (5-40 µmol/L) also inhibited high glucose-induced expression of VCAM-1 and E-selectin at the gene and protein levels. Furthermore, geniposide (5-20 µmol/L) decreased ROS production and prevented IκB degradation in the cytoplasm and NF-κB 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, suggesting 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-κB signaling pathway activation by geniposide.

Insulin and IGF1 receptors in human cardiac microvascular endothelial cells: metabolic, mitogenic and anti-inflammatory effects

“…The lack of insulin or IGF1 effects is in agreement with observations made with HUVECs (Balaram et al 1997, Montagnani et al 2002, Madonna et al 2004. High glucose concentrations (20 mmol/l or higher) was found to increase E-selectin expression in HUVECs after incubation for 24 h or longer (Zheng et al 2008, Wang et al 2010. We incubated our cells in high concentration glucose for 4 h, which could explain the absence of a glucose effect.…”

Dasatinib induces lung vascular toxicity and predisposes to pulmonary hypertension

“…Since oxidative stress is an important determinant of endothelial dysfunction and vascular injury and intracellular ROS potently stimulate EC adhesion molecule expression (25,26), we hypothesized that dasatinib may lead to increased intracellular ROS in pulmonary ECs, thereby inducing EC apoptosis. Double staining on rat lungs with the endothelial marker vWF and 8-oxo-2′-deoxyguanosine (8-oxo-dG), a marker of DNA oxidation, revealed that in vivo dasatinib treatment led to an increased expression of 8-oxo-dG in pulmonary ECs in comparison with vehicle-and imatinib-treated rats ( Figure 5A).…”

Phytochemistry, Pharmacological Activities and Intellectual Property Landscape of Gardenia jasminoides Ellis: a Review

“…40 Geniposide inhibited the phosphorylation of downstream target GSK3β which was counteracted by preincubation with LY294002 along with increased expression of GLUT2 41 and restraining the adhesion of monocytes to HUVECs and the expression of CAMs induced by high glucose in treatment for diabetic vascular injury. 42 Ethanolic extract of Gardenia jasminoides inhibited TNF-alpha-induced NF-kappaB activation, adhesion molecule expression, and monocyte-endothelial interaction in the mechanism of treating vascular diseases, such as atherosclerosis. 43 Geniposide up-regulated the expression of foxp3, promoted Treg-cell-associated cytokines (TGF-β1 and IL-10) cells and ameliorated the atherosclerotic lesions progression partly through lipids regulation and immunoregulation 44 while its metabolite genipin suppressed the intracellular lipid accumulation and also significantly increased the intracellular expression of a fatty acid oxidation-related gene (peroxisomal proliferator-activated receptor: PPARα) so it was confirmed its anti--obesity, insulin resistance-alleviating and abnormal lipid metabolismalleviating effects.…”