Ongoing projects

Anti-inflammatory iridoids and alkaloids from some widely used and some less explored medicinal plants. 01/01/2021 - 31/12/2024

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)

Research team(s)

Chair Tilman - Olive polyphenols and cardiovascular health 01/12/2020 - 30/11/2023

Abstract

In this Chair research focuses on extracts and polyphenols of olive (Olea European), and their function in maintaining cardiovascular health. Cardiovascular diseases are one of the most important causes of death worldwide, and they remain the most important one in Belgium. Research of this Chair will contribute to the knowledge of the role of olive and olive polyphenols in maintaining cardiovascular health. The antioxidant, anti-inflammatory, lipid lowering and anti-hypertensive activity of olive polyphenols and standardized olive extract will be investigated in depth. The effects of olive polyphenols will be studied in a clinical trial in metabolic syndrome patients with elevated blood lipid parameters and slightly elevated blood pressure, as well as in models of oxidative stress and inflammation. In addition, the biotransformation of olive polyphenols by the human gut microbiome will be investigated in the validated GIDM-Colon model, and the effects of formed metabolites on the cardiovascular system will be studied.

Researcher(s)

Research team(s)

Protective effects of nutritional polyphenols and their metabolites towards mechanisms contributing to arterial stiffness. 01/10/2020 - 30/09/2024

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)

Research team(s)

Development and validation of analytical methods for quality control of herbal food supplements (ANAHERBAFOOD). 28/10/2019 - 31/12/2021

Abstract

The Royal Decree KB 29.08.1997 updated in 2017 (KB 24.01.2017 ), imposes the criteria and analytical requirements to which herbal food supplements (containing plants) must comply. These requirements are defined as "does not contain detectable amounts of …" or specify a "maximalamount of ..." a particular compound or class of compounds. However, in many cases appropriate analytical procedures are lacking or not adequate. The general objective of this project is to develop and validate analytical methods to detect (and to establish detection limits) or to quantify concerned products.

Researcher(s)

Research team(s)

Research in het domain of Natural Products and Food. 23/08/2019 - 31/12/2021

Abstract

This gift is related to a clinical trial which is conducted by NatuRA research group. This double blind, placebo and active product controlled clinical trial is investigating the effects of Pycnogenol on Attention-Deficit-Hyperactivity-Disorder (ADHD).

Researcher(s)

Research team(s)

The role of autophagy in the prevention of oxidative stress and cardiovascular disease by olive polyphenols. 01/10/2018 - 30/09/2022

Abstract

Atherosclerotic plaque rupture is the leading cause of acute cardiovascular syndromes and is responsible for 3.9 million deaths in Europe every year. Preventive strategies are greatly needed to reduce the health care burden of cardiovascular disease (CVD). It is well-known that the Mediterranean diet results in a lower CVD risk, with virgin olive oil as an important element. Many of the health-promoting effects are ascribed to the olive polyphenols. Over the years, studies have shown that olive polyphenols reduce oxidative stress and inflammation and enhance vascular function. In recent literature, these effects were related to the upregulation of autophagy. Autophagy is a cellular housekeeping mechanism and autophagy deficiency is detrimental in the development of CVD. Thus, inducing autophagy is likely to be an effective preventive strategy. Olive polyphenols were identified as natural autophagy inducers, but further research is needed to define the contribution of this mechanism to their antioxidant and atheroprotective effects. Therefore, we will determine the most potent autophagy-inducing olive polyphenol in endothelial cells (ECs) and vascular smooth muscle cells (VSMCs) and define the underlying molecular mechanisms linked to autophagy. The most potent polyphenol will be selected for further in vivo analysis, in which we will identify its effects on the functionality of healthy blood vessels, CVD prevention and oxidative stress, with a special focus on the role of EC and VSMC autophagy. This project will give insight in the mechanism of action of olive polyphenols and is an important step towards the implementation of olive polyphenol-based nutraceuticals for the prevention of CVD.

Researcher(s)

Research team(s)

Effect of a polyphenol-rich plant extract on Attention-Deficit Hyperactivity Disorder (ADHD): a randomised, double blind, placebo and active product controlled multicenter trial. 01/01/2018 - 31/12/2021

Abstract

Methylphenidate (MPH, e.g. Rilatine, Medikinet, Concerta), the first choice medication for Attention-Deficit Hyperactivity Disorder (ADHD), is associated with several adverse effects like insomnia and decreased appetite. In addition, ADHD has been associated with immune and oxidantantioxidant imbalances, which offer potential for certain nutritional supplements as ADHD therapy. A commercially available extract from Pinus pinaster, Pycnogenol®, has antioxidant and immunomodulatory activities. One small randomised trial suggests therapeutic benefit from Pycnogenol® in ADHD, though this study had several limitations. This project is therefore a randomised, double blind, parallel multicenter trial to compare the effect of Pycnogenol® to MPH and placebo over a ten week period on the behaviour of 144 ADHD and Attention-Deficit Disorder (ADD) patients. The ability of Pycnogenol® to improve ADHD or ADD behaviour will be evaluated in week 5 and 10. Evaluations of effects on immunity, oxidative stress and other psychiatric/physical complaints (to investigate mechanism of action) will be performed in week 10 as compared to baseline. Acceptability evaluations will be performed in week 10, based on adherence, dropouts and reports of adverse events. Dietary habits will be taken into account. Patients will be recruited from the university hospitals of Antwerp and Ghent, as well as ZNA Erasmus hospital (Antwerp).

Researcher(s)

Research team(s)

Past projects

Prospective investigation of oxidative stress in West Nile virus Infection (PROWENI PILOT). 20/10/2020 - 19/07/2021

Abstract

"WNV infection is the most common cause of epidemic encephalitis in humans in Europe and the United States. West Nile Neuro-invasive Disease (WNND) develops in 1% of infected individuals; it has a 10% case fatality rate and is associated with long-term neurologic and cognitive sequelae in survivors. WNV penetrates the blood-brain barrier, invades the central nervous system and causes necrosis and apoptosis of neurons, but the extent of neuronal injury encountered in brain regions with similar viral load varies widely. We hypothesize that the induction of oxidative stress and autophagy by WNV infection determines the severity of infection and the outcome of neuronal injury in WNV infection. During the 2020 WNV transmission season in Romania, one of the high burden countries in Europe, we will for the first time, comprehensively investigate the sequential intra-host profile of a panel of established markers of oxidative stress and autophagy in plasma, erythrocytes, Peripheral Blood Mononuclear Cells, serum and urine in human WNV cases (n=10) and age-matched healthy controls (n=5). We will develop multiparameter indexes to measure the redox status and to investigate associations of these indexes with clinical, radiological and neuropsychological outcomes. Elucidation of the role of oxidative stress could lead to new opportunities for pharmacotherapeutic interventions in WNV infections."

Researcher(s)

Research team(s)

The role of autophagy in the prevention of oxidative stress and cardiovascular disease by olive polyphenols. 01/11/2019 - 31/10/2021

Abstract

Atherosclerotic plaque rupture is the leading cause of acute cardiovascular syndromes and is responsible for 3.9 million deaths in Europe every year. Preventive strategies are greatly needed to reduce the health care burden of cardiovascular disease (CVD). The Mediterranean diet results in a lower CVD risk, with virgin olive oil as an important element. Many of the health-promoting effects are ascribed to the olive polyphenols (OPs), which have shown to reduce oxidative stress and were recently linked with autophagy. Autophagy is a cellular housekeeping mechanism and autophagy deficiency is detrimental in the development of CVD. Thus, inducing autophagy is likely to be an effective preventive strategy. OPs were identified as natural autophagy inducers, but further research is needed to define the contribution of this mechanism to their antioxidant and atheroprotective effects. Therefore, we will determine the most potent autophagy-inducing OP in endothelial cells and vascular smooth muscle cells and define the underlying molecular mechanisms linked to autophagy. The most potent OP will be selected for further in vivo analysis, in which we will identify its effects on the functionality of healthy blood vessels, CVD prevention and oxidative stress. This project will give insight in the mechanism of action of OPs and is an important step towards the implementation of OP-based nutraceuticals for the prevention of CVD.

Researcher(s)

Research team(s)

Investigations on selected natural product classes as inhibitors of Advanced Glycation Endproducts (AGEs) and modulators of autophagy 01/10/2017 - 30/09/2019

Abstract

During previous investigations in the host laboratory it has been found that several classes of natural products, i.e. polymethoxy-flavones, biflavonoids, xanthones and quinazoline alkaloids, exhibited AGEs inhibiting properties. AGEs (or Advanced Glycation Endproducts) are implicated in many age-related chronic diseases and in protein ageing, and are associated with diabetic complications, atherosclerosis, neurodegenerative diseases, cancer and the normal ageing processes. AGEs have been found to induce autophagy, a favourable subcellular process contributing to cellular homeostasis and adaptation to stress by removing damaged or unwanted intracellular material. Similar to AGEs, autophagy has been associated with different pathological conditions including heart disease, cancer and neurodegeneration. Autophagy is stimulated in atherosclerosis and in oxidative stress conditions. Therefore, AGEs inhibition and modulation of autophagy were selected as targets to be evaluated and to establish structure-activity relationships for the product classes mentioned above. Both AGEs inhibition and modulation of autophagy are relatively new targets in natural product research. AGEs inhibitors and inducers of autophagy, or a combination of both, may be potentially useful products against degenerative diseases in a broad sense, such as the ones mentioned above.

Researcher(s)

Research team(s)

Revisiting Cocoa: Exploiting the full potential of cocoa raw materials through novel processing (REVICO). 01/09/2017 - 31/08/2021

Abstract

REVICO aims to develop innovative fermentation and downstream processing methods to allow a sustainable and optimal use of various cocoa bean components and their specific applications, in particular regarding flavour and health-promoting components.

Researcher(s)

Research team(s)

From Insect to Surfactant (INFACT). 01/09/2017 - 31/08/2019

Abstract

Aim of this innovation project is the introduction of the black soldier fly as a new sustainable source of lipids, from which "green surfactants" can be produced using green and less poluting chemical synthetic pathways. The project involves (1) purification of insect lipids (solvent extraction followed by traditional and enzymatic degumming methods); (2) production of green surfactants (case studies in cooperation with industrial partners); (3) characterisation of the surfactants produced; (4) perception by consumerrs about the use of insect-derived lipids in non-food products.

Researcher(s)

Research team(s)

Analysis of red yeast rice. 23/03/2017 - 31/12/2017

Abstract

This project represents a formal research agreement between UAntwerpen and on the other hand the client. UAntwerpen provides the client research results mentioned in the title of the project under the conditions as stipulated in this contract.

Researcher(s)

Research team(s)

Unraveling the influence of diseases on the metabolism of xenobiotics by the gut microbiome. 01/01/2017 - 31/12/2017

Abstract

The human lives in symbiosis with millions of micro-organisms. A great amount of bacteria is located in the human gut. These micro-organisms, in combination with their unique genes, are called the gastrointestinal microbiome. Only recently the role of the intestinal microbiome in the formation of metabolites of orally ingested compounds has become evident. Fundamental questions concerning the role of the gut microbiome however remain unanswered for the majority of therapeutic, toxic and diet-derived xenobiotics. The composition of the gut microbiome is quite stable in healthy adults and contributes to the maintenance of a healthy state in adulthood. On the other hand, several pathological states are characterized by a modified composition of the intestinal microflora as already demonstrated in obesity and type 2 diabetes. Therefore, the aim of the project is to develop an integrated experimental platform to identify biotransformation due to the microbiome and to evaluate the influence of different disorders (type 2 diabetes, obesity) on this 'microbiotic metabolism'. The fate of the test compounds (simvastatin, tetrabromobisphenol A and epigallocatechin gallate) in a validated in vitro gastrointestinal dialysis system with a colon phase and in well-characterized phenotypes of healthy people and obese and type 2 diabetic patients, will be studied. Detection and identification of the metabolites will be achieved by advanced analytical techniques.

Researcher(s)

Research team(s)

1H-NMR and LCMS-based metabolomics on human plasma and peripheral blood mononuclear cells (PBMC) for early detection of colorectal cancer. 01/10/2016 - 30/09/2019

Abstract

The functional levels of a biological system include the genome, transcriptome, proteome and metabolome, and the latter is considered as most representative of the phenotype. Tumors develop tumor-specific metabolism that endows them with more predominant proliferation, independent of tissue type, while retaining some metabolic traits of the tissue from which they originated. Exploring the cancer metabolome is considered as a promising way to reveal phenotypic changes related to cancer, and to establish specific biomarkers that may be used in screening for diagnostic and prognostic purposes. Many cancers have a higher cure rate if detected in early stages. Metabolomics is an analytical tool used in conjunction with pattern recognition approaches and bioinformatics to detect metabolites and follow their changes in biofluids or tissue. 1H-NMR spectroscopy and LCMS are the two major spectroscopic techniques used in metabolic analysis. This project focuses on colorectal cancer (CRC). It has been established that, apart from plasma, peripheral blood mononuclear cells (PBMC) may provide potential prognostic biomarkers for disease, and may constitute an excellent starting point for early CRC biomarker discovery. Therefore, the main objective of this project is the metabolomics analysis by 1H-NMR and LCMS of plasma and PBMC from diagnosed CRC patients in various stages and healthy controls, and to establish a set of early biomarkers for this cancer type.

Researcher(s)

Research team(s)

Implementation of a state of the art reference center for pharmaceutical and pharmacological studies in Cuba to support the use of natural product formulations composed of indigenous phytomedicinal and nutraceutical molecules. 13/03/2016 - 31/12/2019

Abstract

The project aims to establish a multidisciplinary reference platform at CIDEM with improved capacity (infrastructure+ know-how/training) in natural drug research and development, which integrates preparation of plant extracts, extraction and purification, analytical and structural characterization, molecular pharmacological evaluation and design and evaluation of appropriate systems of drug delivery, which allows pharmaceutical and pharmacological studies of phytomedicinal and nutraceutical products according to international standards, to stimulate the use of natural products in the National System of Health (NSH) in Cuba.

Researcher(s)

Research team(s)

Development of an integrated strategy to characterize new lead compounds based on natural pro-drugs and their metabolites, applied on antiinflammatory drugs 01/02/2016 - 31/01/2020

Abstract

A novel approach is presented in order to characterize new lead compounds from natural sources. Many natural products are pro-drugs that are metabolized and activated after oral administration. Nevertheless, this aspect is usually overlooked when searching for new therapeutic agents using classical approaches. In this project, Salix spp. (willow bark) and Filipendula ulmaria (meadowsweet) were selected as case studies for the characterization of new leads for anti-inflammatory drugs.

Researcher(s)

Research team(s)

Novel natural producs for healthy ageing from Mediterranean diet and food plants of other global sources (MediHealth). 01/01/2016 - 31/12/2019

Abstract

The main goal of the MediHealth project is to introduce a novel approach for the discovery of active agents of food plants from Mediterranian diet and other global sources to promote healthy ageing. This will be achieved through an extended and well-balanced scheme of researcher's secondments between 5 universities and 4 enterprises from EU and associated countries as well as 4 universities from Third countries.

Researcher(s)

Research team(s)

Investigations on selected natural product classes as inhibitors of Advanced Glycation Endproducts (AGEs) and modulators of autophagy. 01/10/2015 - 30/09/2017

Abstract

During previous investigations in the host laboratory it has been found that several classes of natural products, i.e. polymethoxyflavones, biflavonoids, xanthones and quinazoline alkaloids, exhibited AGEs inhibiting properties. AGEs (or Advanced Glycation Endproducts) are implicated in many age-related chronic diseases and in protein ageing, and are associated with diabetic complications, atherosclerosis, neurodegenerative diseases, cancer and the normal ageing processes. AGEs have been found to induce autophagy, a favourable subcellular process contributing to cellular homeostasis and adaptation to stress by removing damaged or unwanted intracellular material. Similar to AGEs, autophagy has been associated with different pathological conditions including heart disease, cancer and neurodegeneration. Autophagy is stimulated in atherosclerosis and in oxidative stress conditions. Therefore, AGEs inhibition and modulation of autophagy were selected as targets to be evaluated and to establish structure-activity relationships for the product classes mentioned above. Both AGEs inhibition and modulation of autophagy are relatively new targets in natural product research. AGEs inhibitors and inducers of autophagy, or a combination of both, may be potentially useful products against degenerative diseases in a broad sense, such as the ones mentioned above.

Researcher(s)

  • Promotor: Pieters Luc
  • Co-promotor: Apers Sandra
  • Fellow: Velichkova Stefaniya

Research team(s)

Investigation of immune and oxidative stress aberrancies in ADHD and the potential of polyphenol-rich plant extract supplementation in ADHD therapy. 01/10/2015 - 30/09/2017

Abstract

The general aim of this project is to improve understanding of immune and oxidative stress aberrancies in ADHD and to evaluate the effects of supplementation with Pinus pinaster bark extract on behaviour and comorbid symptoms and on immune, oxidative stress and antioxidant biomarkers, as compared to placebo, no intervention and MPH treatment.

Researcher(s)

Research team(s)

Biotechnological and Phytochemical Investigations on Antitumoural and Antigenotoxic Plants. 01/10/2015 - 31/03/2016

Abstract

Plants are known to contain a wide range of antitumoural constituents as well as cancer chemopreventive agents. In this PhD project two plant species have been selected, each of which representative for one of both approaches; i.e. Gloriosa superba as a species containing antitumoural agents, and Erythrina latissima as a species containing cancer chemopreventive agents. The research planned during the applicant's stay at the University of Antwerp will mainly focus on the second plant species and the second approach, i.e. cancer chemopreventive agents that can reduce the carcinogenic effects of contaminants in food and animal feed, such as mycotoxins and especially aflatoxins, which are amongst the most potent carcinogens known. An extract from the South African plant Erythrina latissima and its constituents will be evaluated as detoxifying agents against the genotoxic/carcinogenic effects of mycotoxins. Antigenotoxic effects will be tested against mycotoxin (such as aflatoxin B1) - induced mutagenicity. Bacteria (Ames test and Vitotox test) or human cell lines (comet assay and micronucleus/cytome test) will be exposed to the toxin alone, and in the presence of extract or isolated constituents. The mutagenicity response of both treatments will be compared. After development and validation of an appropriate analytical method, the active constituents will be quantified in the crude extract, and the well-characterised extract will be available in future projects for follow up tests in vivo in rats, and for field tests in cattle, for its protective effect against aflatoxin-induced toxicity (in a bilateral FWO research project with the Onderstepoort Veterinary Institute, South-Africa

Researcher(s)

  • Promotor: Apers Sandra
  • Fellow: Zarev Yancho

Research team(s)

Phytochemical and pharmacological investigations on medicinal plants from Pakistan. 15/07/2015 - 14/07/2016

Abstract

In this project four medicinal plants, more in particular Nymphoides indica, Kickxia ramosissima, Cordia dichotoma and Ferula narthex, traditionally used in Pakistan in two different therapeutic areas, i.e. for antimicrobial purposes or against diabetes and its complications, will be phytochemically and pharmacologically investigated. Constituents will be isolated, identified by means of spectroscopic methods, and evaluated in a range of pharmacological assays related to antimicrobial and antidiabetic activity.

Researcher(s)

Research team(s)

Development of an integrated strategy to characterize new lead compounds based on natural pro-drugs and their metabolites. 01/01/2015 - 31/12/2018

Abstract

Many natural products are pro-drugs that are metabolized and activated after oral administration, but this is usually overlooked when searching for new lead compounds. Here Filipendula ulmaria (meadowsweet) and Herniaria hirsuta are selected as case studies for the characterization of new leads for anti-inflammatory drugs, and drugs for nephrolithiasis. An LC-MS and 1H-NMR platform will be used for the fast metabolomic profiling of plant extracts. Secondly, a dialysis model simulating human gastro-intestinal (GI) metabolization will be applied to activate potential pro-drugs. In addition, the dialysate containing the GI metabolites will be treated with microsomal S9 fractions to mimic liver metabolization. The resulting metabolized samples (before and after S9 treatment) will be profiled in the same LC-MS and 1H-NMR platform, and compared with the original profiles. At the same time all extracts and metabolized extracts will be pharmacologically evaluated in a range of in vitro assays related to anti-inflammatory and anti-nephrolithiasis properties, and all data will be analyzed in a metabolomics approach using multivariate data analysis in order to characterize the pharmacologically active constituents and their metabolites as new lead compounds.

Researcher(s)

Research team(s)

Development of an integrated strategy to characterize new lead compounds based on natural pro-drugs and their metabolites. 01/01/2015 - 31/12/2018

Abstract

A novel approach is presented in order to characterize new lead compounds from natural sources. Many natural products are pro-drugs that are metabolized and activated after oral administration. Nevertheless, this aspect is usually overlooked when searching for new therapeutic agents using classical approaches. In this project, the Nauclea pobeguinii tree, Herniaria hirsuta herb, Salix spp. (willow bark) and Filipendula ulmaria (meadowsweet) were selected as case studies for the characterization of new leads for antimalarial, anti-nephrolithiasis, and anti-inflammatory drugs. LC-MS (Liquid Chromatography – Mass Spectrometry) and NMR (Nuclear Magnetic Resonance Spectroscopy) platforms will be established for the fast metabolic profiling of plant extracts, prepared using comprehensive extraction methods to cover the full range of constituents. Secondly, a gastro-intestinal dialysis model (GIDM) simulating human GI metabolization, will be applied in order to activate potential pro-drugs. In addition, the dialysate containing the GI metabolites will be treated with microsomal S9 fractions to mimic liver metabolization. The resulting metabolized samples (before and after S9 treatment) will be profiled using the same LC-MS and NMR platforms, and compared with the original profiles. At the same time all extracts and metabolized extracts will be pharmacologically evaluated in a range of in vitro assays related to antimalarial, anti-nephrolithiasis and anti-inflammatory properties. Pharmacological and chromatographic/ phytochemical data will be analyzed in a metabolomics approach using multivariate data analysis in order to identify pharmacologically active constituents or metabolites. Targeted isolation and final pharmacological evaluation in vitro and in vivo will yield new lead compounds against malaria, nephrolithiasis and inflammatory diseases.

Researcher(s)

Research team(s)

Development of an integrated strategy to characterize new lead compounds based on natural pro-drugs and their metabolites. 01/10/2014 - 30/09/2017

Abstract

Many natural products are pro-drugs that are metabolized and activated after oral administration. Nevertheless this aspect is usually overlooked when searching for new lead compounds for therapeutic agents. In this project Filipendula ulmaria (meadowsweet) and Herniaria hirsuta have been selected as case studies for the characterization of new leads for anti-inflammatory drugs, and drugs for nephrolithiasis. An LC-MS and 1H-NMR platform will be used for the fast metabolomic profiling of plant extracts, prepared using comprehensive extraction methods to cover the full range of constituents. Secondly, the platform will be extended with a dialysis model simulating human gastro-intestinal (GI) metabolization, which will be applied to activate potential pro-drugs. In addition, the dialysate containing the GI metabolites will be treated with microsomal S9 fractions to mimic liver metabolization. The resulting metabolized samples (before and after S9 treatment) will be profiled in the same LC-MS and 1H-NMR platform, and compared with the original profiles. At the same time all extracts and metabolized extracts will be pharmacologically evaluated in a range of in vitro assays related to anti-inflammatory and anti-nephrolithiasis properties. Pharmacological and chromatographic / phytochemical data will be analyzed in a metabolomics approach using multivariate data analysis in order to characterize the pharmacologically active constituents and their metabolites as new lead compounds.

Researcher(s)

Research team(s)

Protective effects of South African plants on mycotoxin-induced mutagenicity and toxicity. 01/09/2014 - 31/08/2016

Abstract

The aim of the project is to evaluate extracts of South African plants as detoxifying agents against the mutagenic effects of mycotoxins using in vitro bioassays. Such plant extracts may be added to feeds and foods as a chemo-preventive measure against the genotoxic effects of mycotoxins, particularly aflatoxins.

Researcher(s)

  • Promotor: Pieters Luc
  • Co-promotor: Apers Sandra
  • Co-promotor: Verschaeve Luc

Research team(s)

Evaluation of the potential of Boldoa saponins as vaccine adjuvants 15/07/2014 - 14/07/2015

Abstract

Vaccines are one of the most effective health interventions ever developed and remain as one of the best shots to prevent epidemic diseases. Generally, traditional vaccines (live, but attenuated, or inactivated whole organisms) and new generation vaccines (e.g. recombinant proteins, purified antigen and DNA) are poorly immunogenic due to lack of effective immune stimulus. Therefore, adjuvants in vaccine formulations have become increasingly important ingredients to increase the immunological efficiency and improve vaccination schedules. Currently, over 100 potent adjuvants have been reported. However, most of them cannot be licensed for human use because of their undesired side effects. Even the most common chemical adjuvant(s) approved for use in licensed human vaccines (e.g. Alum; FDA approved, but neurotoxic) produce unwanted side effects including pain at injection site, inflammation, lymphadenopathy, granulomas and sterile abscess, among others. Due to toxicity issues, there is a critical need to develop or identify adjuvant molecules that initiate a potent immune response with less reactogenicity and less systemic toxicity. In this study, we propose to identify and investigate benchmarking candidate adjuvants based on saponins from Boldoa purpurascens which are safe and less toxic (preliminary results) than other adjuvant saponins (QS 21). The discovery of new saponin-adjuvant from this study would lead to more efficient vaccines aiming to elicit a specific, protective and long-lasting immunity after vaccination. The central research hypothesis of this study is that new saponins purified from Boldoa leaves and stems would exert the immune adjuvant activity without exhibiting systemic toxicity. To study this hypothesis, we will isolate the saponins and fully characterize their chemical structure. Their haemolytic and cytotoxic activity will be determined and the most promising saponin(s) and/or well characterised saponin fraction(s) will be evaluated in vitro on their potential as vaccin adjuvant.

Researcher(s)

  • Promotor: Apers Sandra
  • Fellow: Hernández Ortega Yannarys

Research team(s)

Inhibition of advanced glycation- and advanced lipoxidation -endproducts (AGEs and ALEs) by phytochemicals from Japanese and Nepalese herbs. 01/01/2014 - 31/12/2014

Abstract

The main goal of this project is to identify the bioactive phytochemicals (focusing on AGEs and ALEs inhibitors) from selected plants, and to investigate the mechanisms of the inhibition. Previous studies on Japanese food habits, in particularly from Okinawan islands, have shown that some local plants consumed regularly are very rich in bioactive phytochemicals and are supposed to contribute to longevity of the local people. Some reports on Nepalese herbs are also revealing the same. Based on pubished evidence that supports the presence of phytochemicals in food from Japan, in particular Okinawa, and assessment of the traditional usages and reported studies on Nepalese herbs, a series of 20 plant species has been selected for the intended study.

Researcher(s)

Research team(s)

Protective effect of South African plants on mycotoxin-induced mutagenicity and toxicity. 01/12/2013 - 30/11/2016

Abstract

Mycotoxins cause animal diseases and decrease production of eggs, milk and meat. Genotoxic or mutagenic effects are amongst the important adverse effects. A mutagenic compound is most often also carcinogenic. Aflatoxins are one of the important mycotoxins and amongst the most potent carcinogens. Other mycotoxins may also be mutagenic and carcinogenic. In this project we intend to evaluate extracts of South African plants as detoxifying agents against the mutagenic effects of mycotoxins. Preliminary research found this to be a very realistic approach which may provide identification of protective substances that can be added to feeds and foods as chemo-preventive measures against the genotoxic/carcinogenic effects of mycotoxins. Extracts of the plants will be prepared and antimutagenic effects will be tested against mycotoxin (such as aflatoxin B1, fumonisin and ochratoxin)-induced mutagenicity. For this, bacteria (Ames test and Vitotox test) or human cell lines (comet assay and micronucleus/cytome test) will be exposed to the toxin alone, and in the presence of extract. The mutagenicity response of both treatments will be compared. The most promising extracts will be fractionated and fractions will again be tested until active compounds are purified. The active compounds will then be quantified in the original extracts, and the well-characterised extracts will be evaluated in vivo in rats for their protective effects against aflatoxin-induced toxicity.

Researcher(s)

Research team(s)

Analyses for the Federal Agency FAVV. 26/11/2013 - 31/12/2013

Abstract

This project represents a formal research agreement between UA and on the other hand FAVV. UA provides FAVV research results mentioned in the title of the project under the conditions as stipulated in this contract.

Researcher(s)

  • Promotor: Apers Sandra

Research team(s)

Investigation of immune and oxidative stress aberrancies in ADHD and the potential of polyphenol-rich plant extract supplementation in ADHD therapy. 01/10/2013 - 30/09/2015

Abstract

The general aim of this project is to improve understanding of immune and oxidative stress aberrancies in ADHD and to evaluate the effects of supplementation with Pinus pinaster bark extract on behaviour and comorbid symptoms and on immune, oxidative stress and antioxidant biomarkers, as compared to placebo, no intervention and MPH treatment.

Researcher(s)

Research team(s)

Analysis of samples. 23/08/2013 - 31/12/2013

Abstract

This project represents a formal service agreement between UA and on the other hand HAS Hogeschool. UA provides HAS Hogeschool research results mentioned in the title of the project under the conditions as stipulated in this contract.

Researcher(s)

  • Promotor: Apers Sandra

Research team(s)

Structure-activity relationship study of cyclopeptide alkaloids as potential new medicines. 01/01/2013 - 31/12/2016

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)

Research team(s)

Phytochemical and pharmacological investigations on medicinal plants from Pakistan. 01/11/2012 - 31/10/2013

Abstract

The aim of this project is the isolation, structure elucidation and phytochemical analysis of biologically active constituents in some selected medicinal plants from Pakistan. Focus of the research project will be on plants used for antimicrobial purposes (against infectious diseases), and on plants used by diabetic patients to relieve diabetic complications or to ameliorate the disease. This work may result in the characterisation of lead compounds for new therapeutic agents, and may provide a scientific basis for the traditional use of the plants investigated.

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Detection and risk evaluation of counterfeit medicines based on their physico-chemical properties. 01/10/2012 - 30/09/2014

Abstract

This project represents a formal research agreement between UA and on the other hand WIV. UA provides WIV research results mentioned in the title of the project under the conditions as stipulated in this contract. The purpose of this project is to evaluate the use of chromatographic (impurity) profiling in the detection and risk evaluation of counterfeit drugs.

Researcher(s)

  • Promotor: Apers Sandra

Research team(s)

Investigation of immune and oxidative stress aberrancies in ADHD and the potential of polyphenol-rich plant extract supplementation in ADHD therapy. 01/10/2012 - 30/09/2013

Abstract

The general aim of this project is to improve understanding of immune and oxidative stress aberrancies in ADHD and to evaluate the effects of supplementation with Pinus pinaster bark extract on behaviour and comorbid symptoms and on immune, oxidative stress and antioxidant biomarkers, as compared to placebo, no intervention and MPH treatment.

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Advanced glycation endproducts (AGEs) inhibitors from Momordica charantia (Bitter lemon) and Citrus depressa (Sikwasha). 01/10/2012 - 30/09/2013

Abstract

Advanced glycation endproducts (AGEs) are a heterogeneous group of compounds that have been implicated in diabetes-related complications. The present project will investigate AGEs inhibition by constituents from two plants, Momordia charantia (Bitter lemon) and Citrus depressa. This study will identify potent anti-AGEs natural compounds, which may serve as lead compounds in the design of new drugs against diabetes and its complications.

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Structure-activity relationship study of cyclopeptide alkaloids as potential new drugs. 01/10/2012 - 31/12/2012

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.

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Phytochemical studies of two plants used in traditional medicine in Pakistan: Ziziyphus oxyphylla and Cedrela serrata. 01/07/2012 - 31/12/2012

Abstract

In this project the biologically active constituents from two medicinal plants from Pakistan, more in particular Ziziyphus oxyphylla (Rhamnaceae) and Cedrela serrata (Meliaceae) will be investigated. Their constituents will be chromatographically isolated, identified by spectroscopic means, and pharmacolligically evaluted in various models.

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Investigations on the active metabolites of promising natural products. 01/01/2012 - 31/12/2015

Abstract

This project comprises the identification of the active metabolites of selected natural products with a proven biological activity. The focus will be on Cranberry (Vaccinium macrocarpon) which is used against urinary tract infections, and the Congolese medicinal plant Nauclea pobeguinii, which showed promising activity against malaria in vitro as well as in vivo. For both plants, in vivo activity may be attributed to the formation of biologically active metabolites. The identification of these active metabolites involves the integrated application of in vitro and in vivo test systems with up-to-date technologies such as LC-MS (Liquid Chromatography – Mass Spectrometry) and LC-NMR (Liquid Chromatography – Nuclear Magnetic Resonance spectroscopy) combined with modern information technology such as MVA (multivariate data analysis) to process large amounts of data. These investigations on metabolites of selected natural products with a proven biological activity represent a challenging research field, whereas the successful completion of the submitted proposal might also lead to the characterisation of potential lead compounds for new drugs.

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Antimalarial constituents and metabolites of Nauclea pobeguinii. 21/06/2011 - 31/12/2013

Abstract

This project will focus on the potential use of strictosamide (isolated from the bark of Nauclea pobeguinii) or its metabolites as a pure chemical entity to be used as an active pharmaceutical ingredient against malaria.

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Method development of tocotrienols in Vitis oil. 01/03/2011 - 28/02/2013

Abstract

This project represents a formal service agreement between UA and on the other hand Hogeschool Hasdenbosch. UA provides Hogeschool Hasdenbosch research results mentioned in the title of the project under the conditions as stipulated in this contract.

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Phytochemical, analytical and preclinical research of plant extracts as potential antitumor therapy. 01/01/2011 - 31/12/2014

Abstract

This project represents a research agreement between the UA and on the onther hand IWT. UA provides IWT research results mentioned in the title of the project under the conditions as stipulated in this contract.

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Establishing a high tech purification platform for the purification of natural or synthetic active compounds. 22/07/2010 - 31/12/2014

Abstract

This project represents a formal research agreement between UA and on the other hand the Flemish Public Service. UA provides the Flemish Public Service research results mentioned in the title of the project under the conditions as stipulated in this contract.

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The use of natural products and standardized herbal preparations for antitumor therapy. 01/07/2010 - 31/12/2014

Abstract

This project represents a formal research agreement between UA and on the other hand a private institution. UA provides the private institution research results mentioned in the title of the project under the conditions as stipulated in this contract.

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Development of an LC-NMR and LC-MS metabolomics platform for structure-activity relationship investigations on selected classes of natural products as new lead compounds for antiplasmodial and antiviral drugs. 01/06/2010 - 31/03/2011

Abstract

A technology platform is developed using LC-MS-DAD and LC-NMR for the metabolomic profiling of medicinal plants. The isolation of only the most promising products, followed by their pharmacological evaluation, may result in lead compounds for new drugs.

Researcher(s)

Research team(s)

Development of an LC-NMR and LC-MS metabolomics platform for structure-activity relationship investigations on selected classes of natural products as new lead compounds for antiplasmodial and antiviral drugs. 01/10/2009 - 30/09/2010

Abstract

In this project a technology platform is developed using LC-MS-DAD and LC-NMR for the metabolomic profiling of promising medicinal plants (in this project Nauclea pobeguinii) in order to characterise secondary metabolites in their complex plant matrix. The isolation of only the most promising products, followed by their biological and pharmacological evaluation, may result in new lead compounds for therapeutic agents.

Researcher(s)

Research team(s)

Metabolic profiling and isolation of active compounds of transgenic Maesa cell cultures. 01/07/2009 - 31/12/2013

Abstract

To increase the biosynthesis of medical important Maesa saponins, hybride Maesa/BY2 cell cultures will be generated. These cell cultures will be analysed using UPLC-MS and the metabolic profile of different cell cultures will be compared by PCA. Using this strategy active saponins will be generated and identified in a more efficient way than the classical Pharmacognosy. Interesting compounds will be tested for their anti-angiogenic activity.

Researcher(s)

  • Promotor: Apers Sandra

Research team(s)

Development of science-based, high quality herbal therapeutics. 01/07/2008 - 22/04/2015

Abstract

Due to the growing interest and use of medicinal plants new companies distributing these products arise rapidly and preparations sold in the US or Asia are freely available via the internet. This kind of non-controlled exposure, i.e. with respect to the indication, dosing, contra-indication and side effects, is questionable. In order to maintain its current positive market position and to be a worthy addition to the Western medicine, phytotherapy should be scientifically sustained and of high quality. The proposed project, i.e. the investigation of the efficacy and non-toxicity and analysing the quality of these products, is of big importance for public health.

Researcher(s)

Research team(s)

Development of an in vitro experimental dialysis-model with colonic-phase to simulate the metabolisation by the gut flora and the resorption of naturally occurring polyphenolic antioxidants from the human diet. 01/07/2008 - 31/12/2012

Abstract

This project comprises the development of a continuous flow in vitro dialysis model with a colonic-phase which simulates the gastro-intestinal tract and permits to investigate the absorption and metabolisation of different food constituents. This study focuses on the metabolisation by the gut flora of polyphenolic food constituents, and the antioxidative effects of the metabolites formed and absorbed.

Researcher(s)

Research team(s)

Saponin biosynthesis in hybrid cells and structures. 01/01/2008 - 31/12/2011

Abstract

Natural hybridisation of plant species comprises a part of the mechanisms contributing to the evolution and diversification of species. By this mechanism new secondary metabolites or new combinations of existing secondary metabolites can be created. A major step in making hybrids is the selection of the desired fusion products. In order to do this a new method improving the capacity of the selection will be investigated. Hybrid cell cultures will be analysed with respect to their growth, saponin production and composition, and genome organisation. The aim is to obtain high producing cell cultures delivering preferably the most active saponins as major compounds.

Researcher(s)

Research team(s)

In vitro and in vivo investigations of metabolisation by gut flora, absorption, and antioxidative activity of polyphenolic constituents of human food. 01/01/2008 - 31/12/2011

Abstract

The first objective of this research project is to determine the in vivo antioxidant profile of plant polyphenols after oral supplementation in animals of some selected standardised plant preparations. However, prior to starting this in vivo evaluation, it is essential to extend the existing battery of assays of the research group with additional methods for the assessment of oxidative damage to other endogenous biomolecules than lipids, such as DNA and proteins. The second objective is the development of an in vitro continuous dialysis model with a colon-phase to study the metabolisation by gut flora of the same selected plant preparations and their polyphenolic constituents, the absorption and the antioxidative properties of their metabolites. The presence of the metabolites formed in the in vitro model will be checked in plasma of the laboratory animals. The in vitro antioxidative profile of the metabolites will be compared with the reduction of in vivo parameters of oxidative stress, in order to validate this in vitro dialysis model. In this way the in vitro dialysis model with colon-phase may be, at least in part, a substitute for experiments in laboratory animals in the future.

Researcher(s)

Research team(s)

Principle component analysis (PCA) of complex data generated by chromatographic and spectroscopic analysis of biological mixtures. 01/01/2008 - 31/12/2009

Abstract

There is a never-ending search for novel molecules with superior pharmaceutical properties. Via an IWT-SBO project the production of novel molecules in plants, through use of combinatorial biosynthesis, was started . Because of the high amount of constructs that will be created to screen for new metabolites, a statistical approach will be necessary. To support the statistics of these analyses principle component analysis (PCA) will be necessary.

Researcher(s)

Research team(s)

Permanent technical support service fot the maintenance and the repair of laboratory instument at UNIKIN. A realization study. 01/12/2007 - 31/03/2009

Abstract

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Research team(s)

LC-MS Analysis of Saponins produced by Combinatorial Biosynthesis. 01/02/2007 - 31/07/2007

Abstract

Screening of natural products is one of the strategies that can be followed in the search for new drugs. Recently an IWT-SBO project was started aiming at the combinatorial biosynthesis of active molecules in plants, more in particular saponins. Therefore in the research group new analytical methods will be developed to analyse, to quantify and to identify new saponins, mainly by means of LC-MS.

Researcher(s)

  • Promotor: Apers Sandra

Research team(s)

Evaluation of the in vivo anti-oxidative effects of standardised plant preparations in a diabetic rat model. 01/07/2006 - 31/12/2010

Abstract

The principal anti-oxidative components of Pueraria lobata, Cynara scolymus en Olea europaea, plants containing high amounts of polyphenols, will be characterised and their in vitro anti-oxidative profile established. Analytical methods will be developed and validated in order to obtain test preparations standardised on these active components. The research project will be completed by the investigation of the in vivo anti-oxidative effects of these preparations in a diabetic rat model.

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Development and validation of a microtiter plate model for the evaluation of biocides against Staphylococcus aureus biofilms. 01/03/2006 - 31/12/2007

Abstract

A biofilm is defined as a microbially-derived sessile or adherent community embedded in a matrix and irreversibly attached to a surface. Since biofilms exhibit a high resistance against biocides, this project will develop a method to detect Staphylococcus aureus biofilms. In addition, several known and new biocides will be evaluated for their capacity to inhibit biofilm growth or to destroy existing biofilms.

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Research team(s)

Combinatorial Biosynthesis in Plants. (Combiplan) 01/04/2005 - 30/09/2009

Abstract

The key objective of the Combiplan project is to establish a combinatorial biosynthesis platform in plants that will allow the semi-rational combinatorial engineering of the biosynthesis of existing and novel secondary metabolites in plant cell tissue cultures. To obtain proof of concept, the research strategy designed will be applied to the metabolite class of the triterpene saponins.

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Investigation of dihydrobenzofuran lignans active against leishmaniasis. 01/04/2005 - 30/09/2005

Abstract

Based on a lead compound active against Leishmaniasis, which belongs to the class of the dihydrobenzofuran lignans, characterised in our laboratory, a more detailed investigation of the structure-activity relationship of these compounds will be carried out. Specific up-to-date methods for the synthesis of lignans, as well as QUASAR (Quantitative Structure-Activity Relationship) techniques, will be used.

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Support maintenance scientific equipment. 01/01/2005 - 31/12/2005

Abstract

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Research team(s)

Development of new antiparasitic lead compounds against malaria, trypanosomiasis en leishmaniasis : a multidisciplinary approach. 01/01/2004 - 31/12/2007

Abstract

Parasitic infections such as malaria, trypanosomiasis and leishmaniasis still make a lot of victims every year, especially in developing countries. The aim of this project is to investigate new lead compounds for drugs against these diseases using a multidisciplinary approach: characterisation of new leads from medicinal plants; further investigations of indoloquinoline derivatives, an existing lead; and design of inhibitors of trypanothionsynthetase and prolyloligopeptidase.

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Research team(s)

Isolation and identification of the cancer chemopreventive principles of Calendula officinalis, Pueraria lobata and Calophyllum inophyllum, and establishment of structure-activity relationships. 01/10/2003 - 30/09/2006

Abstract

Cancer claims millions of lives each year. On a world wide basis, cancer represents the single largest cause of death in both men and women. Cancer chemoprevention, a term coined by Sporn in 1976, can be defined as the prevention, inhibition, or reversal of carcinogenesis by administration of one ore more chemical entities, either as individual drugs or as naturally occurring constituents of the diet. Because carcinogenesis is a multistage process there is considerable opportunity for intervention and a number of potential targets for chemoprevention have recently been identified. Based upon the time period during which agents appear to exhibit activity in animal models of carcinogenesis, the major types of chemopreventive agents are: inhibitors of carcinogen formation, 'blocking agents' and 'suppressing agents'. Blocking agents, i.e. inhibitors of tumor initiation, can act by inhibition of carcinogen uptake, inhibition of formation or activation of carcinogen, deactivation or detoxification of carcinogen, preventing carcinogen binding to DNA, or enhancing the level of fidelity of DNA repair. Chemopreventive activity by antioxidant agents includes scavenging reactive electrophiles, scavenging oxygen radicals, and inhibiting arachidonic acid metabolism. Suppressing agents can be described more specifically as inhibitors of tumor promotion/progression. Antiproliferation/ antiprogression activities include, among others, modulation of hormonal and growth factor activity, induction of programmed cell death (apoptosis), and inhibition of angiogenesis. Many classes of natural products, having anti-oestrogenic, anti-inflammatory, antioxidative and/or anti-angiogenic activity, such as carotenoids, isothiocyanates, terpenoids, polyphenols, flavonoids, isoflavones, plant sterols, saponins, lignans and coumarins have shown a great deal of promise. The rationale for this research project is to search molecular evidence for chemopreventive activities shown by three medicinal plants and to link these activities with and establish structure activity relationships for their known and unknown constituents. The work will be focused on, but not limited to, types of constituents for which, based on previous reports, chemopreventive properties can reasonably be expected, but for which the mechanisms of action is mostly unknown.

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Structure-activity relationship investigation in correlation with bioavailability of proanthocyanidins as nutritional antioxidants. 01/01/2003 - 31/12/2006

Abstract

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Research team(s)

Investigation of antioxidant and antiviral natural products from medicinal plants for developing a complementary therapeutical strategy against HSV- and HIV-infections. 01/10/2002 - 30/09/2005

Abstract

In this research antiviral and antioxidant compounds will be isolated from medicinal plants in order to develop a complementary therapeutical strategy against HSV- and HIV-infections.

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01/05/2002 - 30/04/2004

Characterisation of the antimalarial constituents of 4 medicinal plants from Congo. 01/01/2002 - 31/12/2003

Abstract

This project deals with the characterisation of the antimalarial (antiplasmodial) constituents of 4 plants used in traditional medicine in Congo, the activity of which has been confirmed in preliminary in vivo experiments in mice, i.e. Phyllanthus niruri, Cassia occidentalis, Euphorbia hirta and Morinda morindoides. The aim of the project is to find new leads for antimalarial drugs, and to provide a scientific basis for the traditional use of local preparations, including the possibility of standardisation.

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Research team(s)

High pressure liquid chromatographic techniques with fluorimetric detection for the evaluation of antioxidative parameters in vivo and structure-activity assessment of antioxidative natural products. 01/01/2001 - 31/12/2003

Abstract

This project covers the assessment of the in vivo antioxidative properties of natural products. In a first step, rats are stressed with CCl4, after which the concentration of free malondialdehyde and related hydroxyalkenals, determined by means of HPLC, of stressed laboratory animals is compared to the normal, basal concentration. The use of fluorimetric detection enhances both sensitivity and selectivity of the method substantially, important parameters when using small laboratory animals with low MDA plasma concentrations. Subsequently, the in vivo antioxidative effect of some selected polyphenols will be determined, with emphasis on flavonoids and proanthocyanidins. For those compounds structure-activity relationships for in vivo inhibition of lipid peroxidation will be investigated.

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