Beta-sitosterol exhibits anti-inflammatory activity in human aortic endothelial cells.
beta-Sitosterol, normally present in vegetable-containing diets, comprises an important component of cholesterol controlling functional foods. It has been associated with cardiovascular protection, exerting its effect mainly through increasing the antioxidant defense system and effectively lowering the serum cholesterol levels in humans. However, its anti-inflammatory effect on endothelium is unknown. Attachment of leukocytes to the vascular endothelium and the subsequent migration of cells into the vessel wall are early events in atherogenesis, this process requiring the expression of endothelial adhesion molecules. We examined the effect of beta-sitosterol (0.1-200 microM) on (i) the expression of vascular adhesion molecule 1 and intracellular adhesion molecule 1 by cell ELISA and (ii) the attachment of monocytes (U937 cells) in tumor necrosis factor-alpha (TNF-alpha)-stimulated human aortic endothelial cells (HAECs) by adhesion assay. The effect on nuclear factor-kB phosphorylation was also examined via a cell-based ELISA kit. Results showed that beta-sitosterol inhibits significantly vascular adhesion molecule 1 and intracellular adhesion molecule 1 expression in TNF-alpha-stimulated HAEC as well as the binding of U937 cells to TNF-alpha-stimulated HAEC and attenuates the phosphorylation of nuclear factor-kB p65. This study extends existing data regarding the cardioprotective effect of beta-sitosterol and provides new insights into understanding the molecular mechanism underlying the beneficial effect of beta-sitosterol on endothelial function.
Loizou
Stella
S
Department of Biological Chemistry, Medical School, University of Athens, Athens, Greece.
Lekakis
Ioannis
I
Chrousos
George P
GP
Moutsatsou
Paraskevi
P
D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001011:Aorta / Q000166:cytology*; D002316:Cardiotonic Agents; D002448:Cell Adhesion / Q000187:drug effects; D002460:Cell Line; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000737:chemistry / Q000187:drug effects* / Q000502:physiology; D004797:Enzyme-Linked Immunosorbent Assay; D005456:Fluorescent Dyes; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000032:analysis; D009000:Monocytes / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D012855:Sitosterols / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D019010:Vascular Cell Adhesion Molecule-1 / Q000032:analysis
D000893:Anti-Inflammatory Agents; D002316:Cardiotonic Agents; D005456:Fluorescent Dyes; D016328:NF-kappa B; D012855:Sitosterols; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; C025473:gamma-sitosterol