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20 September 2024 | Story André Damons | Photo Supplied
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Zebrafish blue in an aquarium.

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

Faculty of Education hosts global education conference
2015-11-09



The Faculty of Education at the University of the Free State hosted the Annual conference of the South African Education Research Association (SAERA).  From the left are Profs André Keet, Director of the Institute for Reconciliation and Social Justice, Sechaba Mahlomaholo, Dean: Faculty of Education, Carlos Torres, keynote speaker and Professor of Social Sciences and Comparative Education, and former Director of the UCLA-Latin American Center, and Azlam Fataar, SAERA president.

National and global issues, trends, and research were discussed at the annual conference of the South African Education Research Association (SAERA), hosted by the Faculty of Education at the University of the Free State.

Considered as the highlight for educators, education researchers, and education policy makers, this conference is linked directly to the World Education Research Association (WERA), and to the American Education Research Association (AERA).

More than 400 delegates from national and international universities, as well as other interest groups such as the Department of Higher Education and Training of South Africa, have submitted abstracts on a variety of topics, spanning the different disciplines in education.

Keynote Speaker, Prof Carlos Torres, Professor of Social Sciences and Comparative Education, and former Director of the UCLA-Latin American Center, explained the importance of global citizenship education.

“The requirements to enable global citizenship education are clarification, bare essentials, principles, teaching methods, and agents. Global citizenship education is an intervention in search of a theory.”

Prof Torres's areas of theoretical research focus on the relationship between culture and power, the interrelationships of economic, political, and cultural spheres, and the multiple and contradictory dynamics of power among, and within, social movements that make education a site of permanent conflict and struggle.

Prof Teboho Moja, policy researcher and policy analyst for higher education in South Africa, spoke enthusiastically about changes taking place currently in higher education, changes that are driven by the recent demands of university students. Her keynote address dealt with equality and equity in higher education in South Africa.

“This conference is taking place whilst ‘something’ is happening in South Africa. This ‘something’ had to happen to achieve equity in higher education. Recent events on campuses left me proud to see the unity amongst students. Will the next phase in transformation and reform see that the doors of learning will be opened to all, as stated in the Freedom Charter?”

Prof Moja has authored articles on higher education reform issues in areas such as the governance of higher education, policy processes, and impact of globalisation on higher education.

“Hosting a conference of this magnitude validated the research work of the Faculty of Education in particular. It also positioned the Faculty positively in the national and international conversations around education research and gave the Faculty the opportunity to showcase its research, teaching, community engagement, and most importantly its organisational skills,” said Prof Sechaba Mahlomaholo, Dean of the Faculty of Education. According to Prof Mahlomaholo, staff (academic and support) in the Faculty have benefited greatly from listening to and networking with outstanding scholars from across the broad spectrum of education disciplines in the world. “These scholars also role modelled excellence in education research, which both our students and academic staff are now working towards emulating and surpassing,” he said.


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