Inhibitory effects of thunberginols A and B isolated from Hydrangeae Dulcis Folium on mRNA expression of cytokines and on activation of activator protein-1 in RBL-2H3 cells

Abstract

Previously, thunberginols A and B from the processed leaves of Hydrangeae macrophylla var. thunbergii (Hydrangea dulcis folium) substantially inhibited the degranulation caused by antigen and calcium ionophore A23187, and the release of tumor necrosis factor (TNF)-alpha and interleukin (IL)-4 by antigen in RBL-2H3 cells. In the present study, we examined the effect of thunberginol B on the expression of mRNA of several cytokines [ILs-2, 3, 4 and 13, TNF-alpha and granulocyte/macrophage-colony stimulating factor (GM-CSF)] and effects of thunberginols A and B on activator protein (AP)-1 composed of c-jun and c-fos, which is essential for the expression of the cytokine mRNA, in RBL-2H3 cells. Thunberginol B inhibited up-regulated genes of all cytokines, and thunberginols A and B (30 microM) inhibited the phosphorylation of c-jun and expression of c-fos mRNA and phosphorylation of extracellular signal-regulated kinases (ERK1/2). In addition, the profile of gene expression by thunberginol B was similar to that by luteolin, a natural flavone with a potent anti-allergic effect.