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

作　　者：Guang-fa WANG Shao-yu WU Wei XU Hong JIN Zheng-guang ZHU Zhong-huang LI Yuan-xin TIAN Jia-jie ZHANG Jin-jun RAO Shu-guang WU 

机构地区：[1]School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China

出　　处：《Acta Pharmacologica Sinica》2010年第8期953-962,共10页中国药理学报（英文版）

基　　金：Acknowledgements This work was supported by grants from the Science and Technology Bureau of Guangzhou （2006Z1-E6021）, the National Natural Science Foundation of China （No 30901989）, and the Natural Science Foundation of Guangdong Province （No 9151063201000008）.

摘　　要：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.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.

关 键 词：high glucose GENIPOSIDE human umbilical vein endothelial cells cell adhesion molecules vascular cell adhesion mol- ecule-I endothelial selectin nuclear factor-kappa B 

分 类 号：Q26[生物学—细胞生物学] Q786