Nordihydroguaiaretic acid attenuates TNFα-dependent intercellular adhesion molecule-1 expression in cultured human...

During inflammation and oxidative stress, vascular endothelial cell surfaces express high levels of adhesion molecules such as intercellular adhesion molecule 1 (ICAM1) which bind the circulatory leukocytes (e.g. macrophages), through counter receptors LFA/Mac1. The bound leukocytes on sub-endothelial translocation accumulate oxidized lipids and proteins, developing atherosclerotic plaques by foam cell and fatty streak formations. Herewith, nordihydroguaiaretic acid (NDGA) prevails as a polyphenol in the Larrea tridentate plant, with potent antioxidant and anti-inflammatory traits. This study for the first time elucidates that NDGA attenuates TNFα-dependent ICAM1 expression in the cultured human umbilical vein endothelial cells (HUVECs), by targeting the TNFα-PI3K-NF-κB-ICAM1 pathway.

Cultured HUVECs were treated with pro-inflammatory and pro-oxidative cytokine TNFα, to induce ICAM1 mRNA level and protein expression on HUVECs cell surface as documented by northern and western blot, respectively. The effect of varying NDGA concentrations was examined on TNFα-stimulated ICAM1 expression and monocyte attachment assay.

Pre-TNFα-NDGA treatment of HUVECs moderated TNFα-dependent ICAM1 expression and monocyte attachment on vascular endothelium by inhibiting the PI3K-NF-κB-ICAM1 signaling pathway.

In this study, the NDGA anti-inflammatory and anti-adhesion essence is elucidated via impaired cytoplasm to nucleus translocation of pro-oxidative and pro-inflammatory transcription factor NF-κB, moderating the ICAM1 expression and monocyte attachment.