Carsten Gründemann

University Medical Center Freiburg · Department of Environmental Health Sciences

Viola tricolor is a medicinal plant with documented application as an anti-inflammatory herb. The standard of care for the treatment of inflammatory bowel disease is immunosuppressive therapeutics or biologics, which often have undesired effects. We explored V. tricolor herbal preparations that are rich in an emerging class of phytochemicals with d...

Nonpsychotic mental diseases (NMDs) affect approximately 15% of pregnant women in the US. Herbal preparations are perceived a safe alternative to placenta-crossing antidepressants or benzodiazepines in the treatment of nonpsychotic mental diseases. But are these drugs really safe for mother and foetus? This question is of great relevance to physici...

Lactic acid (LA) fermentation of dog’s mercury (M. perennis L.) herbal parts was investigated in samples inoculated with either Lactobacteria (Lactobacillus plantarum and Pediococcus pentosaceus, LBF) or whey (WF). Depending on fermentation time, LA concentrations were monitored in a range of 3.4–15.6 g/L with a concomitant pH decline from 6.5 to 3...

Increased activation and proliferation of T lymphocytes plays an essential role in the development of chronic inflammation and autoimmune diseases. Currently used immunosuppressive drugs often do not provide long-lasting relief of symptoms and show a gradual loss of efficacy over time, and are accompanied by various side effects. Therefore, novel i...

IntroductionClassic psychedelics have been shown to exert therapeutic potential for the treatment of various psychiatric disorders, neuropsychiatric diseases, and neuronal damage. Besides their psychopharmacological activity, psychedelics have been reported to modulate immune functions. There has thus far been a sparse exploration of the direct imm...

Essential oils (EOs) and their individual volatile organic constituents have been an inherent part of our civilization for thousands of years. They are widely used as fragrances in perfumes and cosmetics and contribute to a healthy diet, but also act as active ingredients of pharmaceutical products. Their antibacterial, antiviral, and anti-inflamma...

When confronted with non-psychotic mental disorders, pregnant women often refrain from using synthetic drugs and resort to herbal medicines such as St. John’s wort, California poppy, valerian, lavender, and hops. Nevertheless, these herbal medicines have not yet been officially approved in pregnancy due to lack of safety data. Using a variety of in...

Modern phytotherapy is part of today’s conventional evidence-based medicine and the use of phytopharmaceuticals in integrative oncology is becoming increasingly popular. Approximately 40% of users of such phytopharmaceuticals are tumour patients. The present review provides an overview of the most important plants and nature-based compounds used in...

Background Cannabis sativa L. extracts (CSE) are used for treating inflammatory conditions, but little is known about their immunomodulatory effects. We investigated a novel CSE with high (14%) CBD and low (0.2%) THC concentration in comparison with pure CBD on primary human lymphocytes. Methods Proliferation, cell cycle distribution, apoptosis/ne...

Some plants used in Traditional Chinese Medicine serve as treatment for disease states where a suppression of the cellular immune response is desired. However, the compounds responsible for the immunosuppressant effects of these plants are not necessarily known. The immunosuppressant compounds in the roots of Scutellaria baicalensis, one of the mo...

Pregnancy is a critical period for medical care, during which the well-being of woman and fetus must be considered. This is particularly relevant in managing non-psychotic mental disorders since treatment with central nervous system-active drugs and untreated NMDs may have negative effects. Some well-known herbal preparations (phytopharmaceuticals)...

The cyclotide T20K inhibits the proliferation of human immune cells and is currently in clinical trials for multiple sclerosis. Here, we provide novel functional data and mechanistic insights into structure–activity relationships of T20K. Analogs with partial or complete reduction of the cystine knot had loss of function in proliferation experiment...

Cyclotides are plant-derived peptides found within five families of flowering plants (Violaceae, Rubiaceae, Fabaceae, Solanaceae, and Poaceae) that have a cyclic backbone and six conserved cysteine residues linked by disulfide bonds. Their presence within the Violaceae species seems ubiquitous, yet not all members of other families produce these ma...

In a screening of an extract library from plants used in Traditional Chinese Medicine the MeOH extract of Toddalia asiatica inhibited proliferation of human primary T cells with an IC50 of 25.8 μg/mL. Activity in the extract was tracked by HPLC activity profiling, and a total of 15 compounds were characterized. Three compounds, toddalic acid (6) an...

Resins from various Boswellia species have a long track record in different cultures as a treatment for inflammatory diseases. This study was designed to provide evidence for the anti-inflammatory capacity and medicinal use of Boswellia carteri (Burseraceae). A dichloromethane (DCM) extract of B. carteri gum resin and isolated compounds thereof wer...

The need for novel drugs for the treatment of autoimmune diseases is high, since available pharmaceuticals often have substantial side effects and limited efficacy. Natural products are a good starting point in the development of immunosuppressive leads. Since enhanced T cell proliferation is a common feature of autoimmune diseases, we investigated...

Background Vegan diet (VD) has improved inflammatory activity in patients with rheumatoid arthritis (RA) in several small controlled trials. The underlying mechanism remains widely unclear. We investigated the effect of a VD in comparison to a meat-rich diet (MD) on markers of inflammation (which have been shown to be relevant in patients with RA)...

Purpose: Tumor cells have the capacity to secrete immunosuppressive substances in order to diminish dendritic-cell (DC) activity and evade immune responses. Furthermore, tumor cells express checkpoint programmed death ligands 1 and 2 (PD-L1 and-L2), which bind to their receptors, called programmed-death 1 and 2 (PD-1 and-2), on activated T lymphocy...

Novel immunomodulating agents are currently sought after for the treatment of autoimmune diseases and cancers. In this context, a screening campaign of a collection of 575 cyanobacteria extracts for immunomodulatory effects has been conducted. The screening resulted in several active extracts. Here we report the results of subsequent studies on an...

Vegans are at an increased risk for certain micronutrient deficiencies, foremost of vitamin B12. Little is known about the short-term effects of dietary change to plant-based nutrition on vitamin B12 metabolism. Systemic biomarkers of vitamin B12 status, namely, serum vitamin B12 and holotranscobalamin, may respond quickly to a reduced intake of vi...

Background: The application of mushrooms for health purposes has a long tradition and is very common in Asian countries. This trend is also becoming increasingly popular in the western hemisphere. However, mushrooms from European tradition are being treated in a restrained manner despite having significant potential as drugs or as sources of pure...

A library of extracts from plants used in Chinese Traditional Medicine was screened for inhibition of T lymphocyte proliferation. An ethyl acetate extract from aerial parts of Artemisia argyi showed promising activity and was submitted to HPLC-based activity profiling to track the active compounds. From the most active time window, three guaianolid...

Ethnopharmacological relevance The improvement of wound healing has always been an important issue for both ethnopharmacological and modern medical research. In this study, we used state-of-the-art methods to investigate extracts of plants used traditionally in Nepal for more than 1000 years to treat inflammatory injuries. Aim of the study We focu...

Objectives: Over time different systems were developed for the characterization of individuals according to their physical and psycho-vegetative traits which until today play a role in complementary medicine. This pilot study aimed at investigating if the concepts of polar constitutional types of anthroposophic medicine and according to Kretschmer...

Objective In Europe extracts of Rosmarinus officinalis were traditionally used for the treatment of rheumatic diseases. We investigated the capacity of standardized aqueous extracts of Rosmarinus officinalis on human primary lymphocyte function in vitro, as activated lymphocytes are an important mediator of rheumatic diseases. Methods Lymphocyte p...

Among the known or suspected risk factors, inflammation plays an important role in infectious and non-infectious pathways leading to cancer. Green tea polyphenols have been associated with reducing inflammation and protection against carcinogenesis, especially in prostate cancer. While most of the research in this field, so far, has focussed on epi...

Equisetum arvense, known as common horsetail, is used for the treatment of inflammatory diseases and is the plant with the highest concentration of silica. Yet it is unknown if the medicinal properties are mediated by its silica content. In the current study, optimal conditions for silica-rich horsetail preparations were identified. Bioactivity of...

Intake of isothiocyanates (ITCs), naturally occurring as hydrolization products from glucosinolates (GLSs) in brassicaceae, has, in epidemiological studies, been weakly to moderately inversely correlated with the risk of colorectal cancer, prostate cancer and lung cancer. Numerous preclinical studies demonstrate chemopreventive mode of actions of I...

Tumor cells have the capacity to secrete immunosuppressive substances in order to diminish dendritic cell (DC) activity and thereby escape from immune responses. The impact of mistletoe (Viscum album) extracts (VAE), which are frequently used as an additive anti-cancer therapy to stimulate the immune response, is still unknown. Using a human cellul...

Datasets underlying Figs 1–9. (XLSX)

Lange is an edible basidiomycete from the family Tricholomataceae. Extracts, fractions, and different metabolites isolated from the fruiting bodies of this mushroom were tested for degranulation-inhibiting activities on RBL-2H3 cells (rat basophils). Dichloromethane extracts decreased degranulation significantly, as did a fraction after column chro...

Because different metals are used in complementary medicine for the treatment of diseases related to a dysfunction of the immune system, this study aimed at determining the immunomodulatory potential of Pb(NO3 )2 , AuCl3 , Cu(NO3 )2 , HgCl2 , AgNO3 , SnCl2 , AsCl3 and SbCl3 at sub-toxic concentrations and at assessing possible toxic side effects of...

Ethnopharmacological relevance: Oak bark has been used since ancient times in Europaen ethnomedicine because of its adstringent, antimicrobial and hemostatic features, e.g. as a remedy for the treatment of wounds and skin diseases. Purpose: Oak bark tannins are considered as bioactive natural products, interacting with surface proteins of mucous...

Background Medications from Anthroposophical Medicine (AM) are clinically used for the treatment of infections within a whole medical system but have not yet been evaluated regarding antibacterial effects. The aims of this study was to investigate antibacterial activity of AM medications in cell culture. Methods Screening of AM drug registers for...

Inonotus hispidus is used as a traditional medicine in China. Previous investigations revealed promising immunomodulatory activity of fruit body extracts of I. hispidus. Bioactivity-guided fractionation showed that hispolon and hispidin were active substances. In this study, we analysed the effects of I. hispidus extract and selected constituents o...

Nasal spray from lemon and quince (LQNS) is used to treat hay fever symptoms and has been shown to inhibit histamine release from mast cells in vitro. Forty-three patients with grass pollen allergy (GPA) were randomized to be treated either with placebo or LQNS for one week, respectively, in a cross-over study. At baseline and after the respective...

Oak bark tannins are known for their astringent, anti-inflammatory and desiccating properties, mainly by interacting with mucosal surface proteins. As a consequence, they are used for treatment of dermatological disorders, eczemas and allergies. Since evidence exists for anti-allergic properties of tannin-containing plant extracts, we evaluated the...

Significance Multiple sclerosis (MS) imposes substantial economic burdens on patients, their families, and society. Until now, there are few therapies available, but often unattractive parenteral application or severe side effects are serious issues. This study highlights the use of circular peptides as orally active T-cell-specific immunosuppressi...

Extracts from Shiitake mushrooms (SME) are promoted for health claims, especially for their immunomodulatory effects but references reveal that contamination with bacterial lipopolysaccharides may provide false positive results. Therefore, we characterised chemical and biological aspects of commercial and experimental SME. Pure β-glucan and lipopol...

Preparations from anthroposophical medicine (AM) are clinically used to treat inflammatory disorders. We wanted to investigate effects of a selection of AM medications for parenteral use in cell-based systems in vitro. Colchicum officinale tuber D3, Mandragora D3, Rosmarinus officinale 5 % and Bryophyllum 5 % were selected for the experiments. Indu...

Isothiocyanates (ITC) from the Brassicaceae plant family are regarded as promising for prevention and treatment of cancer. However, experimental settings consider their therapeutic action without taking into account the risk of unwanted effects on healthy tissues. In the present study we investigated the effects of Eruca sativa seed extract contain...

The embryotoxic potential of three model sediment samples with a distinct and well-characterized pollutant burden from the main German river basins Rhine and Elbe was investigated. The Fish Embryo Contact Test (FECT) in zebrafish (Danio rerio) was applied and submitted to further development to allow for a comprehensive risk assessment of such comp...

Ethnopharmacological relevance: In Romanian folk medicine, Helleborus niger L. is used for the treatment of rheumatoid arthritis or viral infections and in complementary therapy, especially in anthroposophic medicine (AM), where the plant is administered as an adjuvant to treat malignant diseases. In the present study, we investigated the differen...

In Europe, extracts of Equisetum arvense (common horsetail) have a long tradition in the treatment of inflammatory disorders. To understand the molecular basis for its use, we investigated the immunomodulatory capacity of a standardized commercially available common horsetail extract on human primary lymphocyte function in vitro. The standardized...

Ethnopharmacological relevance: Heartsease (Viola tricolor L.), a member of the Violaceae family, has a long history as a medicinal plant and has been documented in the Pharmacopoeia of Europe. Due to its anti-inflammatory properties it is regarded as a traditional remedy against skin diseases, for example for the treatment of scabs, itching, ulce...

Cyclotides are a diverse and abundant group of ribosomally synthesized plant peptides containing a unique cyclic cystine-knotted topology that confers them with remarkable stability. Kalata B1, a representative member of this family of mini-proteins, has been found to inhibit the proliferation of human peripheral blood mononuclear cells. Analysis o...

Effects of a cyclotide all-D-enantiomer on cell proliferation of primary activated human lymphocytes and purified T-cells. The influence of medium (ctrl), or kalata B2 and its all-D-enantiomer (D-kalata B2) at various concentrations (1.8-7 µM) on proliferation of activated primary lymphocytes (A) and purified T-cells (B) was measured by cell divisi...

Folding/cyclization and purification of [T20K] kalata B1. (A) HPLC profile of [T20K] kalata B1 after a one-pot oxidation/cyclization procedure. The late eluting peak (indicated with an asterisk) was confirmed to be the correctly folded [T20K] by NMR spectroscopy (Figure 1). (B) The purity of [T20K] kalata B1 was evaluated by analytical RP-HPLC. The...

Effects of cyclotide mutants on cell proliferation of activated primary purified human T-cells. The proliferation capacity of CFSE-labeled primary purified T-cells were analyzed at day 3 in the presence of medium (ctrl), camptothecin (CPT, 30 µM), cyclosporin A (CsA, 0.8 µM) or different concentrations of the kalata B1 cyclotide mutants (1.8-14 µM)...

Ca2+-release in human T-cells. (A) The fluorescence time course of Fura-2 loaded human primary T-cells was measured by extinction at 340 and 380 nm, respectively and emission at 510 nm in 30 sec intervals, while continuously shaking. Ca2+-influx was initiated by adding compounds to the cells (illustrated by the arrow). To receive maximum Ca2+-relea...

Ethnopharmacological relevance: Extracts from Veronica officinalis L. are traditionally used for the treatment of lung diseases; however, the effective compounds and the mode of action are still unknown. Aim of the study: Here we analyzed the effects of a standardized Veronica extract on genes expression and signalling protein production associa...

Background The diversity in nature has long been and still is one of thebiggest resources of pharmaceutical lead compounds andmany natural products ofte n exhibit biological activityagainst unrelated biological targets, thus providing us withstarting points for drug development. Natural peptides ofgreat number and diversity occur in all organisms f...

Triterpenoids from birch bark, like betulin, seem to have an anticancer potential which needs to be further investigated. Aim of this study was first to explore whether a cyclodextrin-solubilised triterpenoid extract (STE) from birch bark induces selective cytotoxic effects in primary liver cancer cells compared to healthy human hepatocytes. Second...

Cyclotides are an abundant and diverse group of ribosomally synthesized plant peptides containing a cyclic cystine-knotted structure that confers them with remarkable stability. They are explored for their distribution in plants, although little is known about the individual peptide content of a single species. Therefore, we chemically analyzed the...

The objective of this study was to determine the effect of birch leaf (Betula pendula) extract (BPE) on corneal inflammation following keratoplasty in the rat model. T cells were stimulated in vitro in the presence of BPE. Proliferation, activation phenotype and the number of apoptotic/necrotic cells in cell culture were analyzed by flow cytometry....

This study aimed to investigate the immunomodulatory and antiallergic properties of preparations from lemon, Citrus medica L. (citrus), and quince, Cydonia oblonga Mill. (Cydonia), which are used in pharmaceutical products to treat patients suffering from allergic disorders. Preparations were analyzed with respect to their impact on the degranulati...

Combudoron, composed of extracts from arnica and stinging nettle, is used for the treatment of partial thickness burns and insect bites in Europe. Because clinical investigations are lacking we wanted to investigate its efficacy in partial thickness burns. Two individuals performed a self experiment: 4 experimental grade 2 burns (each 1 cm(2)) on t...

Gencydo®, a combination of lemon (Citrus limon) juice and aqueous quince (Cydonia oblonga) extract has been used traditionally in anthroposophical medicine for treating patients with allergic rhinitis or asthma. Because there are no reports about the mode of action, we investigated the anti-allergic effects of this preparation in vitro by using cel...

Leaf extracts of Betula pendula have been traditionally used for the treatment of patients with rheumatoid arthritis (RA) or osteoarthritis. We investigated the anti-proliferative capacity of an aqueous leaf extract of Betula pendula (BPE) on human primary lymphocytes in vitro, because activated lymphocytes play a major role in the initiation and m...

The killer cell lectin-like receptor G1 (KLRG1) is expressed by NK and T-cell subsets and recognizes members of the classical cadherin family. KLRG1 is widely used as a lymphocyte differentiation marker in both humans and mice but the physiological role of KLRG1 in vivo is still unclear. Here, we generated KLRG1-deficient mice by homologous recombi...