Research Emmy Tuenter

Abstract

Sea cucumbers, a class of marine echinoderms, are traditionally used as a culinary delicacy, as well as in medicine, in particular in Asia. However, the scientific exploration of their potential health benefits lags behind. This project aims to bridge this gap by comprehensively investigating the bioactive constituents of commercially relevant Holothuria sea cucumber species. Objectives: - Perform a non-targeted chemical profiling of Holothuria extracts using UHPLC-HRMS. - Screen extracts for anti-inflammatory, antiviral, antifungal, and cytotoxic activities. - Purify, isolate and elucidate the structures of promising bioactive compounds. - Assess the biotransformation of active constituents after oral intake using an in vitro gastrointestinal dialysis model (GIDM). - Identify potential marker compounds for the chemotaxonomic classification of Holothuria species. Significance: This research holds promise for: - Uncovering novel bioactive compounds from sea cucumbers with potential applications in functional foods or drug discovery. - Providing a scientific basis for the use of sea cucumbers in traditional medicine. - Developing tools to support the sustainable use of sea cucumber populations, more specifically by assessing the potential of chemotaxonomic classification. Methodology: Various chromatographic and spectroscopic techniques (flash chromatography, HPLC-DAD, semi-preparative LC-DAD-MS, NMR) in combination with a series of in vitro bioassays to assess anti-inflammatory, antifungal, antiviral and cytotoxic properties will be employed. Multivariate statistical analysis will guide the isolation and structure elucidation of bioactive compounds. Using the GIDM model, their stability and absorption characteristics in the gastrointestinal tract will be evaluated. Marker compounds for species identification will be identified through UHPLC-HRMS and NMR analysis. Expected Outcomes: - Identification and characterization of novel bioactive compounds from sea cucumbers. - Increased understanding of the gastrointestinal biotransformation of fractions and bioactive compounds from sea cucumbers - Initiating a robust approach for the chemotaxonomic classification of Holothuria species, which may contribute to the sustainable use and conservation of marine resources. This research project aligns with the NatuRAPT group's mission to explore natural products with human health benefits. It expands the group's expertise into marine bioactive compounds and paves the way for future research in this domain.

Researcher(s)

• Promoter: Tuenter Emmy

Research team(s)

• Natural Products & Food Research and Analysis - Pharmaceutical Technology (NatuRAPT)

Project type(s)

• Research Project

Abstract

Nuclear Magnetic Resonance (NMR) is a spectroscopic technique that provides unique insight into the chemical structure and conformational dynamics of molecules. It is indispensable for medicinal and organic chemistry, for natural products research and for all related domains drawing on organic chemistry. For all publications in these fields, journals demand that research data are extensively supported by NMR-analysis: if NMR data are not or only partially delivered, research cannot be accepted for publication. This is because NMR spectroscopy is a sui generis methodology for which no generally applicable alternatives exist. There are currently only two operating NMRs left at UAntwerpen (both 400 MHz): one in the Medicinal Chemistry research group (UAMC) and one in the Organic Synthesis group (ORSY). In both groups, a large number of externally and internationally funded projects entirely rely on these very intensively used machines. Loss or temporary drop-out of a remaining instrument would have ruinous consequences on research. The available spectrometer at UAMC will be 15 years old in 2024 and at the end of its expected life-time. We therefore would like to replace the UAMC NMR. Spectrometers working at 400 MHz are the literature standard for most medicinal, organic and natural products applications and are expected to remain so for the next two decades. This application also fits in a long-term strategy to ensure that NMR-dependent research remains possible at UAntwerp.

Researcher(s)

• Promoter: Augustyns Koen
• Co-promoter: Billen Pieter
• Co-promoter: Elvas Filipe
• Co-promoter: Maes Bert
• Co-promoter: Prothiwa Michaela
• Co-promoter: Tuenter Emmy
• Co-promoter: Van Der Veken Pieter

Research team(s)

• Medicinal Chemistry (UAMC)

Project type(s)

• Research Project

Abstract

Ellagitannin-rich herbal remedies are used traditionally because of their anti-inflammatory activity. This is connected not to the ellagitannins themselves but to their metabolites produced by the gut microbiota. Urolithin A (UroA) is recognized as the most significant of all ellagitannins' metabolites. However, not everyone is able to have it produced in their gut. The UroA production is exclusive to the hosts of urolithin metabotype A (UM-A) and B (UM-B) and is most probably dependent on the gut microbiota composition and activity. Preliminary trials showed that UM-A hosts have a lower risk of cardiovascular disease. Moreover, the transition from UM-A to other metabotypes is also connected to aging, which might suggest losing certain beneficial abilities. The identity of microorganisms that differentiate UroA producers were not yet revealed. If recognized, new probiotics might be designed. Providing non-UM-A hosts with the possibility to produce UroA efficiently would grant them an advantage due to reports of a wide range of proven and indicated UroAs biological activities. The project aims to isolate, characterize and preserve bacterial strains able to produce UroA from the fecal samples of UM-A and UM-B donors. This will be possible due to innovative substrate conversion screening strategies and novel metabolomic and sequencing techniques utilization. Results will provide missing insights about urolithin metabotypes for further explanatory studies focused on the elucidation of UM-dependant features. Moreover, bioinformatic tools will be developed to obtain multi-omic descriptions of the studied processes, combining metabolomic and targeted metagenomic data. The project will deliver protocols and data analysis methods that will enable us to run advanced projects in the field of natural products biotransformation research. The established pipelines will be suitable also for dysbiosis, xenobiotic-microbiome interaction and pre- and probiotic design studies.

Researcher(s)

• Promoter: Pieters Luc
• Co-promoter: Hermans Nina
• Co-promoter: Laukens Kris
• Co-promoter: Tuenter Emmy
• Fellow: Popowski Dominik

Research team(s)

• Natural Products & Food Research and Analysis - Pharmaceutical Technology (NatuRAPT)

Project type(s)

• Research Project

Abstract

Broad objective: To document traditional medicines used in management of Sickle Cell Disease (SCD) and malaria in Tanzania, and evaluate their efficacy, safety and active phytochemicals. Specific Objectives: i. To document traditional medicines used in the management of SCD and malaria in Tanzania. ii. To determine the in vitro anti-sickling and antiplasmodial activities of the crude extracts of Tanzanian medicinal plants used for the management of SCD and malaria. iii. To determine safety profile of the selected medicinal plants used in the management of SCD and malaria in Tanzania. iv. To identify bioactive compounds with the anti-sickling activity of the compounds from most promising traditional medicines used in the management of SCD in Tanzania. v. To identify bioactive compounds with the antiplasmodial activity of the compounds from most promising traditional medicines used in the management of malaria in Tanzania.

Researcher(s)

• Promoter: Pieters Luc
• Promoter: Tuenter Emmy

Research team(s)

• Natural Products & Food Research and Analysis - Pharmaceutical Technology (NatuRAPT)

Project type(s)

• Research Project

Abstract

Due to global warming and increased sun exposure, skin cancer has a high incidence and increasing prevalence within the Cuban population. An extract obtained from the local marine plant Thalassia testudinum, rich in polyphenols, has shown effective photoprotection properties and antitumor activity against skin cancer. Until now, the extract production implicates the collection of the species from its natural habitat. However, such approach may endanger biodiversity and eco-sustainability as T. testudinum (known as turtle paste) nurtures other species and plays a central role in the coral reef-seagrass-mangrove ecosystem, which in turn protects the dune from extreme weather events, the coastal communities and the archipelago itself. To preserve the environment, ecological alternatives will be developed for efficient production of secondary metabolites facilitated by abiotic elicitors via bioreactor, tissue culture and plant biotechnology. The obtained biomolecules will next be conjugated to nanostructures to promote synergistic biological effects and to increase therapeutic efficacy. Altogether, environmental friendly and eco-sustainable production strategies will be developed for novel safe and effective pharmaceutical formulations from T. testudinum applicable in the prophylaxis of skin cancer, a serious health problem in Cuba. The overall goal is to strengthen training of gender balanced male and female researchers and build up institutional infrastructure capacities in blue (marine) and green (plant) biotechnology applications to improve health of the Cuban population and to stimulate sustainable eco-friendly circular bio-economy in Cuba. The uptake and outreach of the solutions here achieved may improve international visibility of local institutions, reinforcing global citizenship while education, access to scientific advancement and its benefits, health and human welfare (basic human rights) are improved.

Researcher(s)

• Promoter: Vanden Berghe Wim
• Co-promoter: Pieters Luc
• Co-promoter: Tuenter Emmy

Research team(s)

• Cell death signaling (CDS)

Project type(s)

• Research Project

Abstract

Many acute and chronic diseases are either driven or modulated by inflammation. This project focuses on 3 classes of natural products that hold great promise towards anti-inflammatory targets, i.e. oxindole alkaloids and phenanthridone alkaloids, both acting on the NF-kB pathway; and iridoids targeting COX activity. Because of their potential activity against NF-kB, a series of oxindole alkaloids will be isolated from Uncaria tomentosa and U. rhynchophylla, in order to evaluate their NF-kB inhibitory properties. In addition, also the activity on the same target of phenanthridone alkaloids, a poorly explored class of compounds from the Amaryllidaceae family, will be evaluated. Many iridoid-containing medicinal plants are known for their anti-inflammatory properties, Harpagophytum procumbens (Devil's claw) being a well-known example. Iridoids often occur as glycosides; it has been shown that they have to be hydrolyzed first by beta-glucosidase activity of the microflora in the gastro-intestinal tract, but the structures of the ultimately active compounds are not known. In the present project iridoid glycosides will be isolated from H. procumbens, and several in vitro approaches will be followed to prepare and to characterize the metabolites, which will then be evaluated for inhibition of COX-1/2 activity. Finally, a human pilot study will be carried out to detect and to quantify in blood plasma the metabolites that were active in vitro.

Researcher(s)

• Promoter: Pieters Luc
• Promoter: Tuenter Emmy

Research team(s)

• Natural Products & Food Research and Analysis - Pharmaceutical Technology (NatuRAPT)

Project type(s)

• Research Project

Abstract

In order to be able to exert biological activity, phytochemicals which are administered orally need to be absorbed from the gut and reach the general circulation. In our lab, simulations with a gastrointestinal dialysis model with colon phase (GIDM-colon) are already performed to assess gastrointestinal biotransformation and passive absorption. However, active absorption and efflux mechanisms, causing flow of metabolites from the enterocytes towards the gut lumen, are not taken into account. With the current Small Research Grant we intend to expand our GIDM-colon set-up with the MIVO® device (Multi In Vitro Organ device). This device can be seeded with human intestinal tissue and thus can mimic the intestinal barrier to replicate human intestinal absorption. Since it is a continuous double flow system, it is devoid of some of the drawbacks of classical Caco-2 cell experiments. Chlorogenic acid and rutin, two phenolic phytochemicals that are widely present in food, are selected as model compounds to assess the performance of this new device. Experiments will be performed with these two compounds as such and after addition to faeces samples. Results will be compared to previously obtained results of our GIDM-colon system and to in vitro and in vivo literature data.

Researcher(s)

• Promoter: Roth Lynn
• Promoter: Tuenter Emmy

Research team(s)

• Physiopharmacology (PHYSPHAR)

Project type(s)

• Research Project

Abstract

Arterial stiffness, a major health issue, progresses with age. Dietary polyphenols improve vascular stiffening via vascular, inflammatory and other mechanisms, most likely due to their metabolites. Although promising effects for prevention and treatment of arterial stiffness have been reported for blueberry and olive polyphenols, it is largely unknown which polyphenol metabolites interact with which underlying mechanisms. In this project, polyphenol metabolites will be generated in gastrointestinal and liver simulations and will be identified subsequently. Since gut microbial composition is linked to arterial stiffness, is affected by polyphenols and is different in the elderly, an aged and young biotransformation model will be compared. Metabolites will be tested, separately and in mixtures analogous to the in vivo situation, in assays on vascular, oxidative, inflammatory and other mechanisms contributing to arterial stiffness. Also, polyphenol effects on gut microbial composition will be evaluated. This combination of analyses renders this project innovative and original. Results will provide a unique insight on polyphenol metabolism and the influence of age thereupon, and on polyphenol prebiotic-like effects. Moreover, they will increase understanding regarding the influence of olive and blueberry polyphenol metabolites on fundamental processes underlying arterial stiffness and multiple other pathological conditions, facilitating future research.

Researcher(s)

• Promoter: Hermans Nina
• Co-promoter: Roth Lynn
• Co-promoter: Tuenter Emmy
• Fellow: Lauwers Stef

Research team(s)

• Natural Products & Food Research and Analysis - Pharmaceutical Technology (NatuRAPT)

Project type(s)

• Research Project

Abstract

The general aim of this project is to combine the LC-MS and LC-NMR platform available in the Laboratory of Pharmacognosy and Pharmaceutical Analysis (Department of Pharmaceutical Sciences, University of Antwerp) for the characterisation of cyclopeptide alkaloids, a promising class of natural products, from selected plant sources, followed by their targeted isolation, and establishment of structure-activity relationships in several pharmacological models.

Researcher(s)

• Promoter: Pieters Luc
• Co-promoter: Hermans Nina
• Fellow: Tuenter Emmy

Research team(s)

Project type(s)

• Research Project

Abstract

The general aim of this project is to combine the LC-MS and LC-NMR platform available in the Laboratory of Pharmacognosy and Pharmaceutical Analysis (Department of Pharmaceutical Sciences, University of Antwerp) for the characterisation of cyclopeptide alkaloids, a promising class of natural products, from selected plant sources, followed by their targeted isolation, and establishment of structure-activity relationships in several pharmacological models.

Researcher(s)

• Promoter: Pieters Luc
• Co-promoter: Apers Sandra
• Co-promoter: Hermans Nina
• Fellow: Tuenter Emmy

Research team(s)

Project type(s)

• Research Project