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Abstract: The flowers of Inula britannica L. var. chinensis (Rupr.) Reg. (Compositae) are used in traditional medicine to treat asthma, chronic bronchitis, and acute pleurisy in China and Korea. However, the pharmacological actions of Inula britannica L. var. chinensis on endothelial cells and inflammatory monocytes are not clear. In this study, we investigated whether bigelovin, a sesquiterpene lactone isolated from the flowers of Inula britannica L. var. chinensis, inhibits monocyte adhesion and adhesion molecule expression in brain endothelial cells. We measured tumor necrosis factor-α (TNF-α)-enhanced Raw264.7 monocyte binding to brain endothelial cells and the levels of cell adhesion molecules, including vascular adhesion molecule-1 (VCAM-1), intracellular adhesion molecule-1 (ICAM-1), and endothelial-selectin (E-selectin) on the surface of brain endothelial cells. Bigelovin significantly inhibited these in a dose-dependent manner without affecting cell viability. Furthermore, bigelovin suppressed the nuclear factor kappaB (NF-κB) promoter-driven luciferase activity, NF-κB activation, and degradation of NF-κB inhibitor protein alpha (IκBα). These results indicate that bigelovin inhibits inflammatory monocyte adhesion to endothelial cells and the expression of VCAM-1, ICAM-1, and E-selectin by blocking IκBα degradation and NF-κB activation. [Copyright &y& Elsevier]

Abstract: Tilianin has been shown to down-regulate TNF-α induced expression of vascular cell adhesion molecules in endothelial cells. In this study, we examined the anti-atherogenic effects and molecular mechanism of tilianin in vitro and in vivo. Male low-density lipoprotein receptor null mice (Ldlr−/−) fed a high cholesterol diet showed significant increases in the size of atherosclerotic lesions, as well as increased plasma levels of total cholesterol, triglycerides, and the pro-inflammatory cytokines TNF-α and IL-1β, when compared with Ldlr−/− mice fed a normal diet. Mice fed the high cholesterol diet supplemented with tilianin showed significantly reduced lesion sizes and reductions in cytokine levels, without significant changes in serum cholesterol levels. Primary cultured peritoneal macrophages from Ldlr−/− mice showed increased level of TNF-α andIL-1β mRNA in response to treatment with lipopolysaccharide; these increases were inhibited by co-treatment with tilianin. Moreover, tilianin inhibited NF-κB activation, as determined by electrophoretic mobility shift and NF-κB promoter assays. Upstream of NF-κB activation, tilianin inhibited IκB kinase activation and the subsequent phosphorylation and degradation of IκBα protein. These results suggest that tilianin ameliorates atherosclerosis by inhibiting the production of the NF-κB-dependent pro-inflammatory cytokines, TNF-α and IL-1β, via the inhibition of IκB kinase activity. [Copyright &y& Elsevier]