Vasorelaxing Activity of Ulmus davidiana Ethanol Extracts in Rats: Activation of Endothelial Nitric Oxide Synthase

Ulmus davidiana var. japonica Rehder (Urticales: Ulmaceae) (UD) is a tree widespread in northeast Asia. It is traditionally used for anticancer and anti-inflammatory therapy. The present study investigated the effect of an ethanol extract of UD on vascular tension and its underlying mechanism in rats. The dried root bark of UD was ground and extracted with 80% ethanol. The prepared UD extract was used in further analysis. The effect of UD on the cell viability, vasoreactivity and hemodynamics were investigated using propidium iodide staining in cultured cells, isometric tension recording and blood pressure analysis, respectively. Low dose of UD (10~100µg/ml) did not affect endothelial cell viability, but high dose of UD reduced cell viability. UD induced vasorelaxation in the range of 0.1~10µg/ml with an ED50 value of 2µg/ml. UD-induced vasorelaxation was completely abolished by removal of the endothelium or by pre-treatment with L-NAME, an inhibitor of nitric oxide synthase. UD inhibited calcium influx induced by phenylephrine and high K+ and also completely abolished the effect of L-NAME. Intravenous injection of UD extracts (10~100 mg/kg) decreased arterial and ventricular pressure in a dose-dependent manner. Moreover, UD extracts reduced the ventricular contractility (+dP/dt) in anesthetized rats. However, UD-induced hypotensive actions were minimized in L-NAME-treated rats. Taken together, out results showed that UD induced vasorelaxation and has antihypertensive properties, which may be due the activation of nitric oxide synthase in endothelium

Repression of TNF-α-induced IL-8 expression by the glucocorticoid receptor-β involves inhibition of histone H4 acetylation

Increased expression of a number of proinflammatory genes, including IL-8, is associated with inflammatory conditions such as asthma. Glucocorticoid receptor (GR)β, one of the GR isoforms, has been suggested to be upregulated in asthma associated with glucocorticoid insensitivity and to work as a dominant negative inhibitor of wild type GRα. However, recent data suggest that GRβ is not a dominant negative inhibitor of GRα in the transrepressive process and has its own functional role. We investigated the functional role of GRβ expression in the suppressive effect of glucocorticoids on tumor necrosis factor (TNF)-α-induced IL-8 release in an airway epithelial cell line. GRβ expression was induced by treatment of epithelial cells with either dexamethasone or TNF-α. GRβ was able to inhibit glucocorticoid-induced transcriptional activation mediated by binding to glucocorticoid response elements (GREs). The suppressive effect of dexamethasone on TNF-α-induced IL-8 transcription was not affected by GRβ overexpression, rather GRβ had its own weak suppressive activity on TNF-α-induced IL-8 expression. Overall histone deacetylase activity and histone acetyltransferase activity were not changed by GRβ overexpression, but TNF-α-induced histone H4 acetylation at the IL-8 promoter was decreased with GRβ overexpression. This study suggests that GRβ overexpression does not affect glucocorticoid-induced suppression of IL-8 expression in airway epithelial cells and GRβ induces its own histone deacetylase activity around IL-8 promoter site