Geniposide inhibits high glucose-induced cell adhesion through the NF-kappaB signaling pathway in human umbilical vein endothelial cells.
OBJECTIVE
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-kappaB) and inhibitory factor of NF-kappaB (IkappaB) were determined using Western blot analysis. The translocation of NF-kappaB from the cytoplasm to the nucleus was determined using immunofluorescence.


RESULTS
Geniposide (10-20 mumol/L) inhibited high glucose (33 mmol/L)-induced adhesion of monocytes to HUVECs in a dose-dependent manner. This compound (5-40 mumol/L) also inhibited high glucose-induced expression of VCAM-1 and E-selectin at the gene and protein levels. Furthermore, geniposide (5-20 micromol/L) decreased ROS production and prevented IkappaB degradation in the cytoplasm and NF-kappaB translocation from the cytoplasm to the nucleus in HUVECs.


CONCLUSIONS
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-kappaB signaling pathway activation by geniposide.
Wang
Guang-fa
GF
School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, China.
Wu
Shao-yu
SY
Xu
Wei
W
Jin
Hong
H
Zhu
Zheng-guang
ZG
Li
Zhong-huang
ZH
Tian
Yuan-xin
YX
Zhang
Jia-jie
JJ
Rao
Jin-jun
JJ
Wu
Shu-guang
SG
D002448:Cell Adhesion; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D032062:Gardenia / Q000737:chemistry*; D005947:Glucose / Q000494:pharmacology; D006801:Humans; D039823:Iridoids / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology*; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects; D014471:Umbilical Veins / Q000187:drug effects / Q000378:metabolism
D039823:Iridoids; D016328:NF-kappa B; D017382:Reactive Oxygen Species; C007835:geniposide; D005947:Glucose