Pelargonium sidoides root extract EPs® 7630 stimulates release of antimicrobial peptides from neutrophil granulocytes in human whole blood

EPs® 7630 is an aequous-ethanolic extract from roots of P. sidoides DC. widely used for the treatment of acute bronchitis as well as other ear, nose and throat infections. The pharmacological action of EPs® 7630 includes antimicrobial effects, although the antibacterial potential of EPs® 7630 is weak compared with antibiotics. Thus, it is considered that its rapid therapeutic efficacy is primarily mediated via stimulation of innate immune mechanisms rather than direct microbiocidal properties. A key cellular component of the innate immune response is the neutrophil granulocyte, whose cytoplasmic granules contain a variety of antimicrobial proteins and peptides. Among these is the bactericidal/permeability-increasing protein (BPI) and the defensins. These peptides possess broad antimicrobial activity against bacteria, fungi and some viruses, but also exert chemotactic, immunomodulating and wound healing action. The three principal human α-defensins, human neutrophil peptide (HNP) 1–3, account for about 99% of the total defensin content of these cells. Because of the great importance of BPI and HNP for the host defence against infections, it was the aim of the present study to evaluate if EPs® 7630 has an effect on the release of antimicrobial peptides from neutrophils. Investigations were performed with heparinized whole human blood from each 2 male and female donors. Following addition of EPs® 7630at concentrations between 0.3 and 30µg/ml samples were incubated for 5h, then the plasma was collected and the content of BPI and HNP 1–3 was analyzed using commercial ELISA kits. EPs® 7630 concentration-dependently increased the release of HNP 1–3 by up to 150% (30µg/ml) displaying a higher efficacy as lipopolysaccharide (LPS) (+82%, 10ng/ml). In contrast, release of BPI was much stronger stimulated by LPS (+356% at 10ng/ml) than by EPs® 7630 (+127% at 30µg/ml). If a combination of LPS (10ng/ml) and EPs® 7630 (30µg/ml) was applied, release of both groups of antimicrobial peptides was enhanced in an overadditive manner by up to 531 and 294% for BPI and HNP 1–3, respectively. These results demonstrate that EPs® 7630 stimulates the innate host defence by an enhanced release of antimicrobial peptides providing a further rational for its use in the treatment of respiratory tract infections.