Inflammatory bowel disease (IBD) affects the lives of millions of people worldwide due to recurrent, severe symptoms, potential complications, and surgical intervention. The scientific community now defines IBD as a multifactorial disease. An unfavorable constellation of genetic predisposition, harmful environmental and lifestyle factors lead to a disproportion of pathogenic to symbiotic intestinal bacteria (dysbiosis) and disruption of the intestinal barrier. This allows microbial pathogens or products to enter the intestinal submucosa, causing acute, as well as chronic inflammatory responses. Despite this gain in knowledge, IBD treatment still is primarily based on pharmacological immunosuppression. In order to properly address the multi-causality of the disease, complementary therapeutic approaches need to be added to the treatment spectrum.

Preclinical studies show a promising effect of anthocyanin-rich blueberry preparations (Vaccinium myrtillus) on the intestinal microbiome, epithelial barrier, and inflammation in colitis.

This research project will evaluate the effect of freeze-dried blueberry powder in IBD patients with colitis in a three-month prospective controlled observational study. The combination of confocal laser endomicroscopy performed on-site during colonoscopy, the gold standard of functional gut barrier research, primary colon organoid cultures, and molecular biology analyses will allow us to verify the clinical efficacy, as well as the mechanism of action of blueberry therapy on gut barrier function, microbiome, anti-oxidative status, and inflammatory events in colitis patients.

The current worldwide legalization of medical cannabis and the elaboration of monographs for C. sativa flos and C. sativa extracts in the European Pharmacopeia (Ph. Eur.) rise the question about what exactly medical cannabis is. Which pharmacologically active ingredients besides Δ9-tetrahydrocannabinol (THC) und cannabidiol (CBD) at which concentrations should be present in the active pharmaceutical ingredient (API)? In a Federal Office of Public Health (FOPH) approved research project, we profile many different THC and CBD rich cannabis strains based on modern analytical and an innovative receptor pharmacological screening algorithm in vitro. The profiling includes classical cannabinoid receptors, but also ion channels and enzymes that are targeted by cannabinoids. Bioavailable highly active cannabinoids (BHCs), which are often only present in low amounts and specific chemovars, will be investigated in meaningful pharmacological assays also in vivo. The aim of this research project is the development of an ideal API for palliative medicine (drying of flowers, decarboxylation, extract stabilization and formulation). Few aversive effects but pronounced pharmacological effects on pain, sleep, anxiety, and depression, which are frequently observed in palliative patients, shall be achieved. In the framework of this project also pilot studies at the Inselspital Bern are planned. The bioactivity-guided isolation of BHCs with the help of liquid-liquid chromatography (CCC, CPC) will enable the standardization and a rational selection of cannabis varieties for clinical development. The research group is not only specialized in the endocannabinoid system but also has been working on cannabinoid pharmacology for many years in preclinical studies. The group has expertise in the bioanalytics of human blood and the translation of preclinical pharmacological data.

Uncomplicated urinary tract infections (UTI) are one of the most common bacterial infections. The precarious global resistance situation of uropathogens and the high recurrence rate call for the establishment of alternative treatment strategies, with herbal medicines in particular having considerable value. For a large number of drugs traditionally used in UTI, little scientifically robust material is available. The following questions will be addressed:

1. Can herbal materials be confirmed to affect cell physiology and selected virulence factors of UPEC or interaction between human bladder cells and UPEC or cell physiology of bladder/kidney cells? Do the extracts affect the secretion of Tamm-Horsfall protein in the kidney?
2. Herbal urological drugs are often used as combinations of different drugs. Can evidence of synergistic effects of drug mixtures be found?
3. UTI very often break out as recurrent infections after antibiotic therapy. Are there changes in DNA methylation patterns or histones in human bladder and kidney cells that can be attributed to previous infection with UPEC?
4. Some herbal material for UTI have no effect on bacterial virulence factor expression or functionality despite observed efficacy in urinary tract infections. Do herbal urologic drugs affect the methylation pattern of the host genome?
5. The action of some herbal urological drugs requires the mutual interaction between host cells and bacteria. How do UPEC and host cells interact via soluble factors?
6. Can combinations of antibiotics and non-antibiotic compounds produce synergistic effects?

Cohort studies show an association between increased intake of insoluble (cereal) fiber and decreased risk for cardiovascular disease, type 2 diabetes (T2DM), non-alcoholic fatty liver disease (NAFLD), cancer, infectious and inflammatory disorders. Intervention studies, specifically addressing non-fermentable carbohydrates instead of their food sources (whole grain, pulses, legumes) are still sparse. Whole grain trials reported beneficial effects, but cannot pinpoint these benefits on fiber, as minerals, vitamins, grain protein and food matrix contribute to the metabolic results.

The antidiabetic effectiveness of cereal fiber might be explained by a) an increased secretion of incretins and other glucose-induced gastrointestinal hormones, b) an alteration of the gut microbiome, or c) a fermentation to short-chain fatty acids. Fermentable fibers (most of which are soluble) show these mechanisms, but lack strong diabetes-protective associations in cohort studies. In recent supplementation trials, insoluble, mostly non-fermentable fibers improved insulin resistance, glycemia and inflammation in patients with metabolic syndrome or prediabetes.

Between 2022-2024, we want to assess the effectiveness of insoluble, poorly fermentable cereal fiber in a shorter intervention period in patients with high responsiveness (insulin-naïve overt type 2 diabetes mellitus with insulin resistance and NAFLD), using a fiber drinking supplement. Our triple-blinded RCT compares the metabolic effects and mechanistic outcomes of isocaloric treatments with 15 grams of oat-fiber supplement per day (vs. placebo) in 92 patients, covering an intervention period of 12 weeks.

Rheumatoid arthritis (RA) is a very common autoimmune disorder. Patients affected by RA show a chronic systemic inflammation that can determine both articular and bone injuries as well as a progressive functional disability, with an important impact on quality of life, social and economic aspects. The discovery of safe natural products for the RA treatment is needed also because drugs long-term use can cause severe side effects.

In this context, the aims of this project are:

• to evaluate and characterize the effect of phyto-preparations, composed by a mixture of propolis and P. granatum fruits collected in Southern Italy regions, against a model of RA induced in mice by collagen injection.
• to characterize the in vivo mechanism of action of the combination by analyzing the levels of different cytokines involved in Collagen Induced Arthritis;
• to study the bioactivity of this mixture in 2D and 3D cellular models, to evaluate its efficiency as anti-inflammatory agent and identify its putative molecular targets;
• to provide the quali-quantitative chemical characterization of the phyto-preparation used in the biological assays;
• to provide scientific evidences supporting the conservation and sustainable use of traditional knowledge from the internal areas of Italian regions.

Alzheimer's disease (AD) is a neurodegenerative disorder which represents a major health issue and financial burden for health care systems around the world. In the absence of a cure for this condition, the public health priority has focused on enhancement of cognitive performance in older age and, possibly, prevention of cognitive decline.

Several nutraceuticals have displayed over the years the ability or a strong potential to prevent cognitive impairment. Among these, auraptene and naringenin are natural bioactive compounds derived from peels of Citrus fruits. They showed anti-inflammatory, antioxidant, and neuroprotective effects in preclinical studies, memory improvement in AD mouse models and preservation of cognitive function in healthy elderly, thus representing an appealing strategy for cognitive enhancement. A population of frail elderly with subjective cognitive decline (SCD), a condition at higher risk for incident AD, is an ideal target for early intervention trials.

This is a pilot randomized controlled trial to determine clinical and biological effects of Citrus- phytochemicals in 60 individuals with SCD. Participants will be randomized to receive Citrus- phytochemicals standardized in auraptene and naringenin or placebo for 9 months. Cognitive tests and blood-based biological markers will be done at baseline and at the end of treatment as outcome measures.

Inflammatory bowel disease is a chronic recurring disease of the gastrointestinal tract and can be manifested as ulcerative colitis. In Germany, Austria and Switzerland about 400,000 patients suffer from ulcerative colitis. Hereby, Europe has the highest reported prevalence worldwide with 505 per 100,000 people being affected Symptoms include diarrhea, abdominal cramps, and rectal bleeding. Considering current guidelines, anti-inflammatory and immunosuppressive drugs or biologics are used for treatment. Due to common adverse effects and lack of efficacy of standard therapies, a widespread discovery effort has been launched to identify new drugs from natural sources.

Our scientific project aims to evaluate the use of herbal extracts of Viola tricolor as treatment of chronic inflammatory bowel diseases, especially ulcerative colitis. We have teamed up to perform cell-based signaling, mechanism-of-action and toxicity studies with tea infusions (Ph. Eur.) and experimental herbal violet extracts. Further, we aim to extract, isolate and chemically characterize novel immunomodulatory molecules from these preparations. Development of standardized extract preparation, based on the bioactive compounds of V. tricolor, will be employed. Furthermore, safety and efficacy of optimized herbal violet preparation will be assessed and documented following state-of-the-art Case Reporting guidelines, in a cohort of patients suffering from ulcerative colitis.

Aging is the major risk factor for neurodegenerative diseases. The underlying molecular mechanisms of brain aging involve mitochondrial dysfunction and increased oxidative stress. Several studies indicate that mitochondria are a convergence point in aging as well as in neurodegenerative mechanisms. They play a pivotal role in neuronal cell survival and death as they regulate both. Accordingly, current pharmacological concepts focus on increasing mitochondrial respiration and energy (ATP) production as well as on reducing the generation of free oxygen radicals. In addition, autophagy and mitophagy are important cellular processes responsible for breaking down cellular contents therefore preventing the accumulation of damaged biomolecules. Both autophagy and mitophagy are highly impaired during aging.

Wheat germ extract is currently used as adjuvant in cancer therapy. Its polyamines, especially spermidine, are reported to prolong the lifespan of mammals, to induce autophagy and to exhibit anti-oxidant properties.

In this study, we aim at assessing the effects of these natural compounds (wheat germ extract and polyamines) on mitochondria in human aging and Alzheimer in vitro models. For that purpose, we will use sophisticated human neuronal cell models, e.g. aged human neurons (generated from fibroblasts of old donors) and human AD neurons (generated from induced pluripotent stem cells).

One hundred years after the devastating Spanish flu, even the implementation of powerful vaccination and the invention of antivirals and antibiotics have not been able to cope with the high morbidity and mortality associated with influenza epidemics and cyclical pandemics. According to the WHO, low respiratory tract (LRT) infections remain the most deadly communicable disease, causing 3.2 million deaths worldwide in 2015. Mainly caused by influenza viruses and picornaviruses, the mortality rate is heavily boosted by bacterial coinfection (lethal synergism).

In this project, we aim at investigating and developing natural product based antimicrobial agents. In previous studies we identified natural starting materials with broad spectrum antimicrobial activities, such as the extracts from Morus root bark and from the native mushroom Gloephyllum odoratum. Within this project we will explore the full antimicrobial potential of these natural products for the development of improved multi-functional therapeutics and for the discovery of desperately needed novel antimicrobial lead structures overcoming resistances. The envisaged investigations will thereby focus on (i) optimized and standardized extract preparations, (ii) their analytical characterization, and (iii) determination of their antiviral spectrum, as prerequisites of (iv) in vivo efficacy and toxicity studies for preclinical development.

Psoriasis is a chronic inflammatory skin disease that frequently affects the joints and is associated with other comorbidities such as obesity and vascular disease. In Central Europe about 2–3 % of the population suffers from psoriasis, about two million in Germany, and 125 million worldwide.

Psoriasis has an enormous negative impact on the affected subjects. Therefore, during the last decade several new biological drugs were developed for the systemic treatment of moderate to severe psoriasis and psoriatic arthritis. These immunological therapies neutralize the effect of various proinflammatory cytokines, such as TNF-α, Interleukin-17 and Interleukin-23, to name a few.

In contrast, no innovative drugs for topical application or medical skin care products, i.e. botanical compounds, have been approved for psoriasis. Because there is a high of medical skin care in the concomitant treatment of mild forms of psoriasis and childhood psoriasis we have designed a scientific project that aims at exploring the effect of natural compounds on psoriasis keratinocytes in vitro and in vivo. Botanical compounds from Centella asiatica (Madecassoide and Asiaticoside), Mahonia aquifolium (Berberin) and Whrightia tinctoria (Triterpenes und Steroles) are of special interest because they have been used in ayurvedic and traditional Chinese medicine for thousands of years.

First, the molecular mechanisms and mode of action of the compounds and plant extracts will be investigated. Subsequently, the substances will be tested in a psoriasis skin equivalent model that will be established especially for this project. Effective substances are expected to reduce keratinocyte proliferation and epidermal thickness, inhibit inflammation and the stress induced response of the endoplasmatic reticulum (UPR).

Finally, a lipophilic ointment for the topical treatment of psoriasis will be developed. The most promising plant extract or compounds from the above specified testing will be incorporated in the vehicle and will be tested for skin tolerance and effectivity, using the standardized psoriasis plaque-test.

Leishmaniasis is one of the 20 communicable diseases currently classified by WHO as neglected tropical diseases (NTDs) affecting economically disadvantaged populations in the tropics. New efficacious, safe and affordable therapies are urgently needed. We have recently shown that Arnica tincture, an approved herbal medicinal preparation, can effectively cure cutaneous Leishmaniasis (CL) caused by Leishmania braziliensis in a golden hamster model. The tested Arnica tincture, applied topically, was even somewhat more efficacious than the standard antimonial therapeutic Glucantime. Based on these very promising results, the current investigation aims at in-depth investigations on the therapeutic efficacy of Arnica preparations for the treatment of this very severe disfiguring NTD. The main aims are to find out (i) whether Arnica is also active against CL caused by other Leishmania species, (ii) to investigate whether isolated Arnica constituents are equally efficacious as the total tincture, or whether the total extract of Arnica tincture is superior to its isolated chemical constituents and (iii) to gain first evidence on the therapeutic usefulness in human patients.

This herbal medicine could become a new efficacious cure, less toxic, more convenient to administer than standard antimonial therapy and affordable for the disadvantaged population usually affected by CL.