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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

PhD students’ voices reverberate across Africa and beyond
2014-01-14

 

Noel Ndumeya, Tinashe Nyamunda, Ivo Mhike and Anusa Daimon
Photo: Hannes Pieterse
The Centre of Africa Studies (CAS) has been recruiting the best young scholars from across the SADC region – with magnificent success. In the span of six months, four PhD students have excelled both on the African continent and abroad.

Anusa Daimon, Noel Ndumeya, Ivo Mhike and Tinashe Nyamunda – the names of these distinguished students. Set against the backdrop of global excellence and competition, they have been awarded several positions at conferences and already published world-wide.

Anusa Daimon’s PhD studies at the CAS focuses on Malawian migrants and their descendants in Southern Africa. It explores issues of identity construction and agency among this group.

Since his arrival at the CAS, Daimon has won two fully-funded awards to attend international conferences and workshops. He was invited to attend the Young African Scholars Conference at Cambridge University in the UK. He also went to Brazil to the IGK Work and Human Lifecycle in Global History Summer Academy. This workshop explored the historical and modern meanings and practices of work in terms of ‘freedom’ and ‘unfreedom’.

Noel Ndumeya holds a special interest in environmental history and the aspects of conservation and conflict. His PhD hones in on land and agrarian studies with specific focus on South Eastern Zimbabwe.

Ndumeya has won an award from the African Studies Association United Kingdom (ASAUK). This earned him an invitation to Nairobi, Kenya, to work with an editor from the Journal of Southern Africa Studies (JSAS).

Ivo Mhike’s research specialises in youth culture and their relationship with the state. In his PhD he uses juvenile delinquency as a window towards an analysis of social constructs of youth behaviour. This includes youth policy and their institutional and administrative links to the state.

Mhike has been invited to attend the CODESRIA Child and Youth Institute in Dakar, Senegal, with the theme: Social Protection and the Citizen Rights of Vulnerable Children in Africa.

Tinashe Nyamunda specialises in African Economic History. His PhD thesis is entitled, “The State and Finance in Rhodesia: A study of the evolution of the monetary system during the Unilateral Declaration of Independence (UDI), 1965–1979”.

Under the direction of his primary supervisor, Prof Ian Phimister and his secondary supervisor, Dr Andrew Cohen, four of his papers have been accepted for publication. Nyamunda also received sponsorship from the Rector’s Office for an edited book collection of which he is the leading author. The book focuses on the many aspects of Zimbabwe’s blood diamonds.

Recently, Nyamunda has contributed papers at conferences in Botswana and Scotland and attended a workshop at Lund University in Sweden. He has also received an invitation from Germany and Oxford to present some chapters of his PhD thesis.

“The centre has provided the best working environment any PhD student can dream of,” Nyamunda said. He continued to remark that the opportunities Prof Jonathan Jansen has created opened up immense possibilities for them.

“Given these fruitful experiences in just a year at the university,” Nyamunda said,” imagine what can be accomplished given the resources and environment availed by the institution.” The prospects after his PhD studies looks bright, he concluded, because of the opportunities provided by the UFS.

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