Anti-Infective Mode of Action of EPs® 7630 at the Molecular Level

Abstract

Clinical trials have shown that EPs® 7630, an aqueous ethanolic extract from the roots of Pelargonium sidoides, is an efficacious treatment for respiratory tract infections. A large body of in vitro studies has provided evidence for an anti-infective principle associated with activation of the non-specific immune system. However, the mode of action at the cellular and molecular level is still insufficiently defined. This study, therefore, aimed to provide further insight into the underlying principles of the therapeutic benefits of EPs® 7630 under these conditions. Using BMMΦ experimentally infected with intracellular bacteria, Listeria monocytogenes, incubation with EPs® 7630 (1 - 30 μg/mL) increased release of NO, production of membrane bound/intra- and extracellular IL-1, IL-12 and TNF-α and changed the expressions of the surface markers CD40 and CD119 at an early time point post infection (6 h) in a concentration-dependent manner in most experiments. Compared with non-infected cells, the effects were more pronounced. LPS + IFN-γ served as positive and untreated cells as negative controls. Analyses were carried out at single cell levels using flow cytometry, while ELISA was additionally utilized for monitoring secreted cytokines. Although the current data provide additional valuable information for understanding the anti-infective effects of EPs® 7630, the triggered signalling pathways associated with host immune responses appear even more complex than anticipated and are evidently not shared by ‘classical’ immunomodulators to this extent.

Abbreviations

APC:allophycocyanin

BMMΦ:bone marrow-derived macrophages

DMSO:dimethyl sulfoxide

ELISA:enzyme-linked immunosorbent assay

FACS:fluorescence-activated cell sorter

FCS:foetal calf serum

IL:interleukin

LPS:lipopolysaccaride

NO:nitric oxides

PBS:phosphate buffered saline

PE:R-phycoerythrin

TNF:tumour necrosis factor

Key words

Pelargonium sidoides - Geraniaceae - EPs® 7630 - nitric oxides - cytokines - surface markers - macrophages - Listeria monocytogenes - experimental infection model

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