5′-Nitro-indirubinoxime inhibits inflammatory response in TNF-α stimulated human umbilical vein endothelial cells

Abstract Inflammation plays a critical role in the development of atherosclerosis and TNF-α, a major inflammatory cytokine, induces inflammatory responses by enhancing the expression of adhesion molecules and the secretion of inflammatory mediators. Indirubin is an active compound of Polygonum tinctorium Lour ( P. tinctorium ) that has the ability to suppress inflammation. Previously, we described the novel indirubin derivative, 5′-nitro-indirubinoxime (5′-NIO), and demonstrated that it has potent anti-proliferative activity against various human cancer cells. In this study, we examined the effect of 5′-NIO on the TNF-α induced inflammatory conditions of human umbilical vein endothelial cells (HUVECs). We found that 5′-NIO inhibited TNF-α induced MCP-1 and IL-8 expression at the RNA and protein levels in HUVECs. Specifically, 5′-NIO significantly inhibited the TNF-α stimulated release of MCP-1 and IL-8, with levels that were only 19.8% and 30.9% of those of untreated control cells, respectively. Furthermore, 5′-NIO largely inhibited the adhesion of U937 cells to HUVECs by decreasing the expression level of ICAM-1 and VCAM-1. Overall, these observations suggest that 5′-NIO has the potential for use as an anti-atherosclerotic agent.