Nuclear factor kappaB-mediated down-regulation of adhesion molecules: Possible mechanism for inhibitory activity of bigelovin against inflammatory monocytes adhesion to endothelial cells

• Published in: Journal of ethnopharmacology 2009-06, Vol.123 (2), p.250-256
• Main Authors: Nam, Kung-Woo, Oh, Goo Taeg, Seo, Eun-Kyoung, Kim, Kyeong Ho, Koo, Uk, Lee, Sung-Jin, Mar, Woongchon
• Format: Article
• Language: English
• Subjects: Animals; anti-inflammatory activity; bEnd.3 cells; Bigelovin; binding proteins; Biological and medical sciences; Brain - cytology; Brain - drug effects; cell adhesion; Cell Adhesion - drug effects; cell adhesion molecules; Cell Line; Dose-Response Relationship, Drug; Down-Regulation - drug effects; E-Selectin - drug effects; E-Selectin - metabolism; endothelial cells; Endothelial Cells - drug effects; Endothelial Cells - metabolism; Flowers; gene expression regulation; Gene Expression Regulation - drug effects; General pharmacology; I-kappa B Proteins - drug effects; I-kappa B Proteins - metabolism; inflammation; Intercellular Adhesion Molecule-1 - drug effects; Intercellular Adhesion Molecule-1 - metabolism; Inula; Inula - chemistry; Inula britannica var. chinensis; Lactones - administration & dosage; Lactones - isolation & purification; Lactones - pharmacology; Medical sciences; medicinal plants; medicinal properties; Medicine, East Asian Traditional; Mice; monocytes; Monocytes - drug effects; Monocytes - metabolism; NF-kappa B - drug effects; NF-kappa B - metabolism; NF-KappaB Inhibitor alpha; NF-κB; Pharmacognosy. Homeopathy. Health food; Pharmacology. Drug treatments; phytochemicals; Sesquiterpenes - administration & dosage; Sesquiterpenes - isolation & purification; Sesquiterpenes - pharmacology; sesquiterpenoid lactones; transcription factors; tumor necrosis factor-alpha; Tumor Necrosis Factor-alpha - administration & dosage; Vascular Cell Adhesion Molecule-1 - drug effects; Vascular Cell Adhesion Molecule-1 - metabolism; VCAM-1
• ISSN: 0378-8741; 1872-7573
• DOI: 10.1016/j.jep.2009.03.017

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.