title: Evaluation of an aqueous-ethanolic extract from Pelargonium sidoides (EPs® 7630) for its activity against group A-streptococci adhesion to human HEp-2 epithelial cells.
abstract: OBJECTIVE
  The root extract of Pelargonium sidoides DC (Geraniaceae), EPs® 7630, is currently used to treat respiratory tract infections. The therapeutic benefits are largely related to the modulation of the non-specific immune system. The present study was designed to investigate the anti-adhesive activity of this herbal medicine with Streptococcus pyogenes as model microorganism and to identify the underlying biologically active principle.
  
  
  METHODS
  Adherence of fluorescent-labelled group A-streptococci (GAS) to human epithelial (HEp-2) cells was assessed by flow cytometry. Anti-adhesive properties of the parent extract as well as a methanol-soluble (MSF) and a methanol-insoluble fraction (MIF) derived thereof were examined. Treatment with skin powder produced polyphenol-free samples which were included for comparison. Anti-adherence studies were extended to a series of highly purified proanthocyanidins including homogenous epicatechin- and catechin-based polyflavans, a 'mixed' procyanidin sample, an A-type proanthocyanidin mixture as well as a prodelphinidin test substance.
  
  
  RESULTS
  After pre-treatment of GAS with EPs® 7630 or its subfractions MIF and MSF at concentrations of 30 μg/ml, adhesion of the pathogen to HEp-2 cells was inhibited by ca. 45%, ca. 35% and ca. 30%, respectively. However, following preincubation of cells with the extract and the fractions no effect was observed. This finding indicates that the anti-adhesive effects are due to interactions with binding factors on the bacterial surface. Since polyphenol-free samples proved to be inactive, proanthocyanidins appear to represent the anti-adhesive principle. Comparative studies with chemically defined proanthocyanidins revealed that the prodelphinidin nature, i.e. the pyrogallol B-ring elements of constituent flavanyl units, represented an important structural feature of the anti-adhesive potential of this herbal medicine.
  
  
  CONCLUSIONS
  The current data provide strong evidence for a potent anti-adhesion principle of the Pelargonium sidoides root extract related to specific proanthocyanidins. This finding suggests an interaction with bacterial binding sites in a specific rather than non-specific manner. However, the blocked adhesion molecules remain to be identified. The anti-adhesive mechanism may well contribute to the anti-infective activity of EPs® 7630 at an early time point of a bacterial infection.
authors.affiliation: Freie Universität Berlin, Institute of Pharmacy, Pharmaceutical Biology, Berlin, Germany.
authors.forename: Aneta
authors.initials: A
authors.lastname: Janecki
authors.forename: Andreas
authors.initials: A
authors.lastname: Conrad
authors.forename: Inge
authors.initials: I
authors.lastname: Engels
authors.forename: Uwe
authors.initials: U
authors.lastname: Frank
authors.forename: Herbert
authors.initials: H
authors.lastname: Kolodziej
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D001422:Bacterial Adhesion / Q000187:drug effects*; D045744:Cell Line, Tumor; D004847:Epithelial Cells / Q000382:microbiology*; D000431:Ethanol; D006801:Humans; D031316:Pelargonium; D008517:Phytotherapy; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D018517:Plant Roots; D013297:Streptococcus pyogenes / Q000187:drug effects* / Q000502:physiology
chemical_list: D000900:Anti-Bacterial Agents; C476332:EPs 7630; D010936:Plant Extracts; D000431:Ethanol