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A researcher from the University of the Free State (UFS) hopes to make living with epilepsy and other diseases of the central nervous system (CNS) easier by using South African plants extracts which may have anti-epileptic properties and testing them on zebrafish larvae.

Prof Anke Wilhelm, Associate Professor and Divisional Head of Organic Chemistry in the UFS Department of Chemistry, focuses her research on the isolation of active GABAergic compounds (substances that affect the brain’s GABA system, which helps control nervous system activity) by using a test that measures the movement of zebrafish larvae.

Even though obtaining regulatory approval for use as a treatment for epilepsy is a long and complex process, Prof Wilhelm hopes to contribute to the better pain management of people suffering from epilepsy and diseases of the CNS through an affordable alternative drug with less side effects.

The tests are done in a zebrafish bioassay (an analytical method to determine the potency of a substance by its effect on living animals) housed at the UFS’ Chemistry Department.

Why zebrafish larvae?

Prof Wilhelm, who is a National Research Foundation Y2-rated synthetic organic chemist, says zebrafish share about 70% of their genes with humans, and about 84% of human genes known to be associated with diseases have a counterpart in zebrafish. This makes them a valuable model for studying human biology and disease.

“Zebrafish are powerful tools for modelling a wide range of CNS diseases, contributing significantly to the understanding of disease mechanisms and the development of potential treatments,” she says. “Mood disorders, anxiety, insomnia, and attention deficit hyperactivity disorder (ADHD) are all diseases which may be studied through this bioassay.”

She explains that the zebrafish larvae are studied seven days after fertilisation in their bioassay. The larvae are incubated with the specific plant extract at a certain (non-toxic) concentration for three hours. Pentylenetetrazol (PTZ), a GABAA receptor antagonist that has been extensively used in rodent models for acute seizure and anxiety, is then administered to induce concentration-dependent seizures in the zebrafish larvae.

“GABA receptor antagonists are drugs that inhibit the action of gamma-aminobutyric acid, the chief inhibitory neurotransmitter in the mammalian central nervous system,” Prof Wilhelm says. “A specialised infrared camera is then used to track the movement of the larvae inside a chamber. The data is then converted into a graph which shows the movement of each larva over 30 minutes.

“If lowering of movement is observed at a specific concentration it means that the plant extract may have the potential to be used as an epileptic drug, since it has the ability to counteract the induced seizure in the larvae. This bioassay is extremely useful in drug discovery and toxicity screening of plant extracts.”

Zebrafish embryos, she says, develop quickly, with major organs forming within 36 hours of fertilisation. This rapid development allows researchers to observe the effects of experiments in a short period. The maintenance of a zebrafish model is less costly and labour-intensive than using a rodent model. “The use of zebrafish larvae allows for high-throughput screening due to their small size and transparency, which facilitates observation of CNS-related effects. Their genetic and physiological similarities to humans make them a valuable model for early-stage drug discovery.”

Potential uses

The next step in the research, according to Prof Wilhelm, is to identify a single compound from a natural source which may have potential anti-epileptic activity while causing less side effects than current drugs on the market. Researchers would then investigate the possibility of synthesising such a compound on a large scale, to eliminate the use of a natural resource and promote sustainability.

“Many plant extracts which I have screened show a synergistic effect in the zebrafish bioassay, meaning that the extract or the combination of compounds shows potential, but the isolated compounds are inactive. Even if a plant extract shows promise in preclinical and early clinical studies, obtaining regulatory approval for use as a treatment for epilepsy is a long and complex process.

“This includes demonstrating consistent efficacy, safety, and quality in large-scale clinical trials. One of the major challenges in using plant extracts is the lack of standardisation. The concentration of active compounds in plant extracts can vary depending on factors like the plant's growing conditions, harvest time, and extraction methods. This variability makes it difficult to ensure consistent efficacy and safety, therefore this is a time-consuming process.”

Green chemistry

After being approached by Dr Glen Taylor, Senior Director of the UFS Directorate Research Development (DRD), in 2017, regarding funding for Noldus Daniovision equipment, Prof Wilhelm received training from Prof Matthias Hamburger of the University of Basel in Switzerland on how to use such equipment. The larval zebrafish locomotive bioassay was established at the UFS Chemistry Department during 2017 and 2018 and now provides a third-stream income for the department, in conjunction with the Department of Genetics, where the adult zebrafish are housed.

Prof Wilhelm’s other research interests include green chemistry, food sustainability, and recycling. She is looking into green extraction techniques using non-conventional extraction methods to recover valuable bioactive compounds from agricultural and food residues. “Techniques like ultrasound, microwave-assisted extraction, and the use of deep eutectic solvents are becoming popular for their efficiency and alignment with circular economy principles.”

News Archive

Research grant holder first to be graded at UFS in NRF’s Thuthuka Programme
2007-11-17

 

In the picture, from the left are: Ms Gudrun Schirge (National Research Foundation), Mr Nico Benson (Directorate Research Development at the UFS), Prof Heidi Hudson (Department of Political Science at the UFS) and Dr Annelize Venter (Co-ordinator of the Thuthuka Programme at the UFS)
Photo: Mangaliso Radebe

 

Research grant holder first to be graded at UFS in NRF’s Thuthuka Programme

Prof. Heidi Hudson, Departmental Chairperson at the University of the Free State's (UFS) Department of Political Science, recently received a C1 grading from the National Research Foundation (NRF).

With this grading she became the first researcher and grant holder in the Thuthuka Programme for young researchers at the UFS to be graded by the NRF.

“The Thuthuka Programme is a capacity building initiative from the NRF which prepares young researchers for grading and provides them with a good grounding for research,” said Dr Annelize Venter, researcher at the UFS Research Development Directorate and co-ordinator of the Thuthuka Programme.

According to Dr Venter, the UFS currently has 44 researchers who receive funding from the Thuthuka Programme for their postgraduate studies. The results of possible entrants to the programme in 2008 are awaited.

”The UFS also received ten researchers additional to the current 69 who have a valid evaluation status. The results of an additional 11 applications are also awaited. Some of these are first applications,” said Dr Venter.

Over and above the grant holders in the Thuthuka Programme, any researcher can apply to be evaluated by the NRF’s Evaluation Centre. The evaluation status of a researcher serves as the norm determinator and the quality of research at a university is measured according to this.

Ms Gudrun Schirge from the NRF presented a workshop today at the UFS to researchers who wanted to apply for grading and evaluation.
Researchers who wished to apply for the re-evaluation of their current evaluation status also attended the workshop.

Ms Schirge was one of the founders of the evaluation system and has been a manager at the Evaluation Centre for the past 20 years. She will be retiring this year and will be involved with the centre on a part-time basis.

Media Release
Issued by: Lacea Loader
Assistant Director: Media Liaison
Tel: 051 401 2584
Cell: 083 645 2454
E-mail: loaderl.stg@ufs.ac.za  
16 November 2007
 

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