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.
Three new 3,4-seco-cycloartanes, secaubryenol (1), secaubrytriol (2), and secaubryolide (3), were isolated from an exudate collected on the aerial parts of Gardenia aubryi, in addition to the known (24S)-cycloartane-24,25-diol-3-one, coccinetane A, herbacetin 3,8-dimethyl ether, hibiscetin 3,8,3',4'-tetramethyl ether, and conyzatin. The structures of 1 and 2 were established by mass spectrometry and NMR experiments, while the relative configuration of 2 was defined unequivocally using X-ray crystallography. The in vitro cytotoxic activity of compounds 1-3 was evaluated against four human solid tumor cell lines.
Chios mastic gum (CMG) is a white, semitransparent, natural resin that is obtained as a trunk exudate from mastic trees. Triterpenic compounds and phytosterols like tirucallol are among its major components. CMG has been associated with cardiovascular protection, exerting its effect mainly through increasing the antioxidant defense system, and effectively lowering the levels of serum cholesterol in human subjects. However, data on its anti-inflammatory effect on endothelium are scarce. Attachment of leukocytes to the vascular endothelium and the subsequent migration of cells into the vessel wall are early events in atherogenesis, and this process requires the expression of endothelial adhesion molecules. In this study, we examined the effect of CMG neutral extract (25-200 microg/ml) and tirucallol (0.1-100 microM) on the following: 1) the expression of adhesion molecules (VCAM-1 and ICAM-1) by Cell ELISA and 2) the attachment of monocytes (U937 cells) in TNF-alpha stimulated Human Aortic Endothelial Cells (HAEC) by Adhesion assay. The impact of treatment with CMG neutral extract and tirucallol in NFkB phosphorylation was also examined by a cell-based ELISA kit. Both CMG extract and tirucallol inhibit significantly VCAM-1 and ICAM-1 expression in TNF-alpha-stimulated HAEC. They also inhibit significantly the binding of U937 cells to TNF-alpha-stimulated HAEC and attenuate the phosphorylation of NFkB p65. This study extends existing data regarding the cardioprotective effect of CMG, expands the spectrum of known phytosterols with potent antiatheromatic activity, provides new insight into the mechanisms underlying the beneficial effect of CMG on endothelial function, and may aid in design of new therapy for intervention in atherosclerosis.
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