Latest research projects (2020-2022)

Resistance induction against herbal isothiocyanates (ITC)

Project description:
The native preparation Angocin® Anti-Infekt N displays high antibacterial activity and is therefore recommended by the National German S 3 Guideline on Uncomplicated Urinary Tract Infection. Three isothiocyanates (ITC) are mainly responsible for the effect shown by Angocin®: benzyl-ITC; allyl-ITC and 2-phenylethyl-ITC, with all three compounds exhibiting good antibacterial properties. However, in contrast to standard antibiotics, ITC act on various structures of the bacterial cell making it more difficult for resistance to emerge. Plant-based antibacterial agents are therefore a good alternative to standard antibiotics. In this project, we will investigate whether herbal ITC, alone or in combination, can induce resistance in different bacterial species.

Project Leader: Frank U
Contact persons: Biehler K, Biehler D Start of project: 01.05.2021
Project end: 30.04.2022 Sponsor: Repha GmbH

Combination effect of herbal ITC and antibiotics against multi-resistant pathogens causing urinary tract infection
Project description

Project description:
Besides standard antibiotic therapy, the 2017 National German S3 Guideline on Uncomplicated Urinary Tract Infection (UTI) approves the native product Angocin® Anti-Infekt N as a treatment option for UTI. The project will investigate whether combination of the AB listed in the S3 Guideline and Angocin® Anti-Infect N enhances antimicrobial potential. Special attention will be paid to multi-resistant bacteria.
Project Leader: Frank U Contact: Biehler K, Biehler D Start of project: 01.05.2020 End of projetc: 30.04.2021 Sponsor: Repha GmbH

Completed research projects (2010 – 2019)

Nasturtium (AiF)

Project description:
The project ” Nasturtium (AiF) ” is funded by the Federal Ministry of Economics and Energy (BMWi) within the framework of the Central Innovation Programme for Medium-Sized Enterprises (ZIM). The aim of the project is to develop a marketable drug based on the volatile isothiocyanates (ITC) contained in nasturtium (Tropaeolum majus) in close cooperation with a leading manufacturer of biological drugs. For this purpose, a special laboratory analysis system will be developed and established that enables controlled quantitative ITC release from the plant tissues. The investigations will also include proof of the antibacterial effect of the new phyto-antibiotic with special consideration of multi- resistant microorganisms as well as its pharmacokinetics and bioavailability in the human organism.

Project Leader: Frank U Contact: Biehler K
Start of project: 01.01.2017 End of project: 31.12.2018
Sponsor: Federal Ministry of Economics and Energy (BMWi)

The antimicrobial activity of herbal isothiocyanates (ITC)

Project description:
To elucidate the mechanisms of action of an antibiotic, it is necessary to know exactly how the substance interferes with vital processes in bacteria. In this regard, it is helpful to compare the protein configuration of bacteria treated with an antibiotic agent. Antibiotics interfere with certain processes in the cell; for example, they inhibit proteins that are important for the construction of the cell membrane. The bacteria try to counteract this interference by, for example, producing more membrane-building proteins. If, following antibiotic treatment, more proteins are found that produce components for cell membrane construction, it is an indication that the tested substance interferes with exactly this process. In-vitro, Enterobacteriaceae belonging to the 3-/4-MRGN group (according to RKI definition) prove to be significantly less resistant to isothiocyanates /(ITC) from powders of horseradish root and nasturtium than those that do not exhibit such a resistance pattern (Mampel et al. 2014). As a result of this discovery, there is increased interest in elucidating the antimicrobial mechanism of action of ITC against human pathogens.

Project Leader: Frank U Contact: Biehler K
Start of project: 01.01.2014 End of project: 30.09.2017
Sponsor: Federal Ministry of Economics and Energy (BMWi)

In-vitro activity of ceftaroline against Methicillin-resistant Staphylococcus aureus (MRSA) from German intensive care patients

Projektbeschreibung:
Ceftaroline, a new cephalosporin with expanded activity against methicillin-resistant Staphylococcus aureus (MRSA) in addition to broad spectrum bactericidal activity against other gram- positive and gram-negative pathogens. Therefore, ceftaroline is a promising agent for antibiotic treatment of complicated skin and soft tissue infections. The purpose of the study is to investigate the in-vitro activity of ceftaroline against methicillin-resistant Staphylococcus aureus (MRSA) strains isolated from patients hospitalized in intensive care units (ICUs) in Germany.

Projektleitung: Frank U Ansprechpartner: Biehler K Projektbeginn: 01.01.2014
Projektende: 30.06.2014 Finanzierung: AstraZeneca GmbH

Studies on the anti-bacterial effect of Angocin® Anti-Infect N on UPEC and antibiotic-resistant Enterobacteriaceae

Project description:
The project was based on investigations on the antibacterial activity of Angocin®Anti-Infect N already completed in cooperation between the Institute for Environmental Medicine and Hospital Epidemiology and Messrs. Repha GmbH. These investigations impressively demonstrated that the preparation exhibits a wide range of antibacterial activity on both Gram-positive and Gram-negative bacteria.

Project Leader: Frank U (Heidelberg) Contact person: Frank U
Staff: Biehler K, Engels I Project start: 01.10.2012
Project end: 30.09.2013 Sponsor: Repha GmbH

DNA microarray investigations on the immunomodulatory activity of Echinacin® on AGPs of monocytes

Project description:
Echinacin® is produced from the pressed juice of the red coneflower (Echinacea purpurea). The healing power of this plant has long been known in the traditional medicine of native American tribes for treatment of inflammation, wounds, burns, fever, and infections of the respiratory tract. The indications claimed for the phytotherapeutic are supportive therapy of recurrent infections of the respiratory and urinary tracts. In the literature, assessment of the efficacy of different echinacea preparations varies: several randomized, placebo-controlled double-blind studies describe a significant effect of Echinacea purpurea (Echinacin®) in treatment of acute common cold (Hoheisel et al., 1997; Schulten, 2001) and a shortening of the duration of the disease (Schulten, 2001). On the other hand, some publications question the effect of echinacea preparations for prophylaxis and therapy of infections of the upper respiratory tract (Caruso & Gwaltney, 2005; Turner et al., 2005). However, when evaluating these publications, it should be noted that in some cases broad generalisations are made based on different echinacea preparations; or that species of echinacea other than Echinacea purpurea have been used. The mechanisms of action of Echinacin® have been described as stimulation of phagocytosis and specific immune mechanisms (stimulation of T and B cell function and increased cytokine expression).

Project Leader and Contact: Frank U (Heidelberg) Deputy: Biehler K (Freiburg)
Project Start: 01.11.2011
Project End: 31.05.2012
Sponsor: Madaus GmbH, Heidelberg University Hospital

Influence of TUIM® urofemin on the interaction between Escherichia coli and human uroepithelial cells

Project description
The consumption of fruits can be beneficial in preventing chronic diseases, as the polyphenols contained in them reduce oxidative stress and strengthen immunity. The proanthocyanidins specifically contained in cranberries have been investigated for their antibacterial effects by various working groups (Wiener Medizinische Wochenschrift 2007; 157/13-14: 325-330). These polyphenolic substances can help prevent infections of the urinary tract by inhibiting fibrinogenic attachment and coagulation of pathogenic bacteria such as Escherichia coli. Randomised, placebo-controlled clinical studies already show that cranberry juice can be used as an infection prophylactic. The anti-adhesive properties of these fruits appear to be dose-dependent, and exploitation of the anti-adhesive effect of cranberries is an innovative and natural approach to dealing with bacterial urinary tract infections. The preparation under investigation, TUIM® urofemin, contains a high-quality natural cranberry extract. Cranberries are a valuable source of nutrition. They are rich in secondary plant substances, which are an important part of our daily diet and perform a variety of protective functions in the human body. In addition to cranberry extract, TUIM® urofeminine contains vitamin C, zinc, and selenium. Together, these three ingredients, which ideally should always be part of our daily diet, boost immune function. A well-functioning immune system is important to be able to fend off ubiquitous bacteria. It is largely unknown whether cranberry extract possesses antibacterial properties against human pathogenic organisms. It is therefore of great interest to investigate whether direct antimicrobial activities can be observed with the extract (i.e. the preparation TUIM® urofemin). Two methods are available for this purpose: The determination of the minimum inhibitory concentration (MIC) by agar-dilution and micro-dilution.

Project Leader and contact: Frank U (Heidelberg) Deputy: Biehler K (Freiburg)
Project start: 2010
Project end: 2012
Sponsor: Dr. Wilmar Schwabe GmbH & Co KG

DNA microarray investigations on the immunomodulatory effect of Angocin® Anti-Infect N on monocytes

Project description:
The effect of mustard oils on the gene expression of the human monocyte cell line THP-1 will be investigated. This will help to clarify the extent to which mustard oils have an immunostimulatory effect. Due to the heterogeneity of plant products, the pure substances will be investigated first, i.e. allyl-ITC, 2-phenylethyl-ITC and benzyl-ITC. Since mustard oils have a toxic effect at higher concentrations and longer exposure times, a separate test series will be established to determine optimum conditions. If it is determined that mustard oils have an immunomodulatory effect, we will investigate whether the native preparation also causes this effect.

Project Leader and Contact: Frank U (Heidelberg) Deputy: Biehler K (Freiburg)
Project start: 01.09.2010
Project end: 31.05.2011
Sponsor: Repha GmbH, Biologische Heilmittel