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Published on: March 24, 2017
Anti-infective mode of action of EPs 7630 at the molecular level
Carsten Thäle1, Albrecht Kiderlen, Herbert Kolodziej
1Institute of Pharmacy, Pharmaceutical Biology, Freie Universität Berlin, Berlin, Germany.
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 BMM phi experimentally infected with intracellular bacteria, Listeria monocytogenes, incubation with EPs 7630 (1 - 30 micro increased release of NO, production of membrane bound/intra- and extracellular IL-1, IL-12 and TNF-alpha 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-gamma 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.
Insights
EPs 7630, a Pelargonium sidoides root extract, enhances immune responses against Listeria monocytogenes by increasing nitric oxide and cytokine production. This extract modulates immune cell surface markers, revealing complex anti-infective mechanisms.
Area of Science:
- Immunology
- Pharmacology
- Microbiology
Background:
- EPs 7630, an extract from Pelargonium sidoides roots, is clinically effective for respiratory infections.
- In vitro studies suggest EPs 7630 activates the non-specific immune system.
- The precise cellular and molecular mechanisms of EPs 7630 remain incompletely understood.
Purpose of the Study:
- To investigate the cellular and molecular mechanisms underlying the therapeutic benefits of EPs 7630.
- To elucidate how EPs 7630 modulates immune responses against intracellular bacterial infections.
Main Methods:
- Bone marrow-derived macrophages (BMM phi) were infected with Listeria monocytogenes.
- Cells were treated with varying concentrations of EPs 7630.
- Nitric oxide (NO), cytokine (IL-1, IL-12, TNF-alpha) production, and surface marker expression (CD40, CD119) were analyzed using flow cytometry and ELISA.
Main Results:
- EPs 7630 treatment increased NO release and production of IL-1, IL-12, and TNF-alpha in infected macrophages.
- Expression of CD40 and CD119 surface markers was altered by EPs 7630 in a concentration-dependent manner.
- These effects were more pronounced in infected cells compared to non-infected cells and observed at an early time point (6 hours post-infection).
Conclusions:
- EPs 7630 triggers significant innate immune responses, including cytokine release and immune cell marker modulation.
- The study provides valuable insights into the anti-infective effects of EPs 7630 at the cellular level.
- The immune response pathways activated by EPs 7630 are complex and distinct from those of classical immunomodulators.
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