Study Of The Molecular Mechanisms Of Emodin Affect Lps-induced Endothelial Cell Inflammatory Response

Emodin [1, 3, 8-Trihydroxy-6-methylanthraquinone] has been reported to exhibit vascular anti-inflammatory properties. However, the relevant anti-inflammatory mechanisms are not well understood. The present study was design to explore the molecular target(s) of emodin in modifying lipopolysaccharide (LPS)-associated signal transduction pathway in human umbilical vein endothelial cells (HUVECs). Cultured HUVECs were preincubated with 1 to 50μg/ml emodin for 30 min, LPS-induced proinflammatory cytokines (IL-1, IL-6) and chemokines (IL-8, MCP-1) expression were inhibited dose-dependently, which agreed well with the NF-κB activation and IκB degradation detected by immunocytochemistry and western blotting, respectively. However, emodin didn't inhibit the IL-1β-induced NF-κB activation and IκB degradation in HUVECs, suggesting that emodin maybe affect the expression of toll-like receptor-4 (TLR-4) or the formation of LPS-receptor complex in the lipid rafts. Further investigation showed that cholesterol binding agent methyl-β-cyclodextrin (MBCD) inhibited LPS induced NF-κB activation in passaged HUVECs (CD14 negative). These results indicate that lipid rafts play a key role in LPS signaling pathway in passaged HUVECs. Moreover, our studies also found that emodin disrupted the structure of lipid rafts on cell membranes by deleting cholesterol from lipid rafts. This action leads to inhibition of LPS-receptor complex formation, which finally suppresses the LPS-induced NF-κB activation and proinflammatory molecules secretion. These novel anti-inflammatory actions of emodin demonstrate that it could play a modulatory role in atherosclerosis or other inflammation-related cardiovascular diseases.