Diarylheptanoids suppress expression of leukocyte adhesion molecules on human vascular endothelial cells

Diarylheptanoids possess potent anti-inflammatory properties. However, the mechanism of their action is not fully understood. In this study, we found that three diarylheptanoids, 1-(3,5-dimethoxy-4-hydroxyphenyl)-7-phenylhept -1-en-3-one (YPE-01), yakuchinone B and demethyl-yakuchinone B, reduced the adhesion of both human monocytic cell line U937 and human eosinophilic cel l line EoL-1 cells to tumor necrosis factor-alpha (TNF-alpha)-treated human umbilical vein endothelial cells. In addition, they suppressed interleukin -1 beta- or TNF-alpha-induced expression of E-selectin, vascular cell adhes ion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) on t he surface of the endothelial cells. Since YPE-01 reduced both VCAM-1 and I CAM-1 mRNA induction in TNF-alpha-stimulated endothelial cells, diarylhepta noids appeared to suppress adhesion molecule expression at the transcriptio nal level. Furthermore, YPE-01 suppressed both VCAM-1 and ICAM-1 mRNA induc tion as well as edema in 12-O-tetradecanoylphorbol 13-acetate (TPA)-inflame d mice ears in vivo. These results suggest that the anti-inflammatory actio n of diarylheptanoids is, at least in part, due to their suppressive effect on the surface expression of inducible adhesion molecules in endothelial c ells, and subsequent leukocyte adhesion. (C) 2000 Elsevier Science B.V. All rights reserved.