Ivy Leaf Dry Extract EA 575[sup.®] Has an Inhibitory Effect on the Signalling Cascade of Adenosine Receptor A[sub.2B]

Ivy leaf dry extract EA 575[sup.®] is used to improve complaints of chronic inflammatory bronchial diseases and acute inflammation of the respiratory tract accompanied by coughing. Its mechanism of action has so far been explained by influencing β[sub.2]-adrenergic signal transduction. In the present study, we investigated a possible influence on adenosine receptor A[sub.2B] (A[sub.2B]AR) signalling, as it has been described to play a significant and detrimental role in chronic inflammatory airway diseases. The influence of EA 575[sup.®] on A[sub.2B]AR signalling was assessed with measurements of dynamic mass redistribution. Subsequently, the effects on A[sub.2B]AR-mediated second messenger cAMP levels, β-arrestin 2 recruitment, and cAMP response element (CRE) activation were examined using luciferase-based HEK293 reporter cell lines. Lastly, the impact on A[sub.2B]AR-mediated IL-6 release in Calu-3 epithelial lung cells was investigated via the Lumit™ Immunoassay. Additionally, the adenosine receptor subtype mediating these effects was specified, and A[sub.2B]AR was found to be responsible. The present study demonstrates an inhibitory influence of EA 575[sup.®] on A[sub.2B]AR-mediated general cellular response, cAMP levels, β-arrestin 2 recruitment, CRE activation, and IL-6 release. Since these EA 575[sup.®]-mediated effects occur within a time frame of several hours of incubation, its mode of action can be described as indirect. The present data are the first to describe an inhibitory effect of EA 575[sup.®] on A[sub.2B]AR signalling. This may offer an explanation for the beneficial clinical effects of the extract in adjuvant asthma therapy.