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Inhibition of mediator release from RBL-2H3 cells and human granulocytes by the Pelargonium sidoides root extract EPs®7630
The incidence of allergic disorders is increasing worldwide. This applies especially to type-I hypersensitivity reactions which are caused by immunoglobulin E (IgE) antibodies against normally innocuous environmental substances. Cross-linking of IgE bound to high-affinity receptors (FcεRI) on mast cells and basophiles by the triggering allergen leads subsequently to the release of inflammatory mediators (e.g. histamine, eicosanoids and cytokines). EPs®7630, a proprietary aquous-ethanolic extract from P. sidoides roots, is an effective treatment for upper respiratory tract infections. Besides other pharmacological effects, EPs®7630 has been shown to possess immunomodulatory properties. Thus, it was considered worthwhile to investigate if EPs®7630 also disposes of anti-allergic activities. Experiments were performed with RBL-2H3 rat basophilic leukemia cells. Dinitrophenyl (DNP)-IgE-sensitized cells were treated with the extract for 30min and then stimulated by DNP-BSA to induce degranulation. Released histamine was determined using a commercial ELISA. EPs®7630 concentration-dependently inhibited release of histamine with an IC50 of about 39µg/ml. In order to gain insight into the contribution of different extract constituents to this effect, EPs®7630 was fractionated by Sephadex LH20 column chromatography using eluents of different polarity. Whereas a water and an ethanol eluate exerted only a very weak effect, a strong inhibition of histamine release was observed for the methanol (IC50 21µg/ml) and acetone fraction (IC50 19µg/ml) indicating that mainly polymeric proanthocyanidins are responsible for this activity. Similarly, the extract suppressed the synthesis of eicosanoids in calcium ionophore-stimulated human granulocytes. The results suggest that EPs®7630 may have a therapeutic potential for the treatment of allergies, such as hay fever or asthma.