Emodin (3-methyl-1,6,8-trihydroxyanthraquinone) inhibits TNF-induced NF-κB activation, IκB degradation, and expression of cell surface adhesion proteins in human vascular endothelial cells

Abstract

Most in¯ammatory agents activate nuclear transcription factor-kB (NF-kB) which results in expression of genes for cytokines, adhesion molecules, and enzymes involved in ampli®cation and perpetuation of in¯ammation. 6, is an active component from the roots of Polygonum cuspidatum that has been reported to exhibit antiinammatory properties but the mechanism is not known. In the present study we investigated the eects of emodin on the activation of NF-kB in human umbelical vein endothelial cells (EC). Treatment of EC with TNF activated NF-kB; preincubation with emodin inhibited this activation in a dose-and time-dependent manner. Emodin did not chemically modify NF-kB subunits but rather inhibited degradation of IkB, an inhibitory subunit of NF-kB. Since the promoter regions of ICAM-1, VCAM-1, and ELAM-1 contain NF-kB binding sites and these adhesion molecules are involved in the attachment of leukocytes to EC, the eect of emodin on the adhesion of monocytes to EC and the expression of these adhesion molecules was also studied. Treatment of EC with TNF for 6 h increased the adhesion of monocytes to EC, which correlated with increases in cell surface expression of ICAM-1, VCAM-1 and ELAM-1. Pretreatment of EC for 1 h with emodin inhibited both monocyte-EC attachment and expression of ICAM-1, ELAM-1 and VCAM-1. These results indicate that emodin is a potent inhibitor of NF-kB activation and expression of adhesion molecules and thus could be useful in treating various in¯ammatory diseases.

An anthraquinone derivative, emodin sensitizes hepatocellular carcinoma cells to TRAIL induced apoptosis through the induction of death receptors and downregulation of cell survival proteins

“…Interestingly, most of the antiapoptotic proteins described above are regulated by pro-inflammatory transcription factor NF-jB [50]. Because emodin has been previously reported to inhibit NF-jB activation [28], it is possible that down-regulation of expression of these proteins is probably due to suppression of NF-jB activation. Also, we have observed that emodin can exert its anticancer effects through the suppression of signal transducer and activator of transcription 3 in HCC cells (unpublished findings) which may also account for its inhibitory effects on various cell survival proteins.…”

“…Emodin exerts its pleiotropic anti-cancer effects through diverse mechanisms including the activation of caspase-3 [23] and upregulation of p53 and p21 [26]. Moreover, emodin has been reported to inhibit the kinase activity/activation of p56lck, HER2/neu [21], casein kinase [27], NF-jB [28], activator protein 1 [29,30], AKT [30], matrix metalloproteinases [29,31], and the expression of chemokine receptor CXCR4 [32]. Our findings specifically in HCC cells clearly indicate that this quinone can enhance TRAIL-induced apoptosis through the downregulation of antiapoptotic proteins, upregulation of death receptors and the activation of C/EBP homologous protein (CHOP).…”

Diverse agents act at multiple levels to inhibit the Rel/NF-κB signal transduction pathway

“…Similar to sanguinarine, emodin can inhibit a variety of kinases, including protein kinase C, c-Src, p56-lck and HER-2. Moreover, emodin can inhibit IkBa degradation after stimulation with TNFa (Kumar et al, 1998). Based on its ability to inhibit other kinases, emodin may act directly on the IKK complex to block phosphorylation of IkBa.…”

Emodin inhibits vascular endothelial growth factor‐A‐induced angiogenesis by blocking receptor‐2 (KDR/Flk‐1) phosphorylation

“…[20][21][22] Emodin additionally exerts anti-inflammatory effects on endothelial cells by inhibiting tumor necrosis factor -induced activation of nuclear factor-kappa B in human umbilical vein endothelial cells (HUVECs). 23 Given that numerous endogenous factors and pharmacological agents that regulate cancer progression and inflammation additionally affect angiogenesis, it seems quite likely that emodin would also affect angiogenesis. In the present study, we investigated whether emodin has anti-angiogenic activity especially on the VEGF-Ainduced angiogenesis, and if so, the critical mechanism of action.…”