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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

UFS congratulates Wayde van Niekerk and other students for their national and international accomplishments
2015-09-17



Kovsies showing the world that success is inevitable
Photo: Johan Roux

Students from the University of the Free State (UFS) have not only conquered South Africa (SA), they have also left footprints in the world. During 2014 and 2015, our students have performed well in various fields.

A special celebratory event was held at the Bloemfontein Campus on Tuesday 15 September 2015. Members of the Rectorate, Student Representative Council (SRC), Grey College Secondary School personnel and former principal, Mr Johan Volsteedt, as well as UFS staff members and students gathered at the Callie Human Centre to congratulate those students who have recently represented the university with excellence atnational and global levels. Also present were representatives from the Department of Sports Arts Culture and Recreation (SACR) in the Free State and the Free State Sport Confederation (FSSC).

Sports leadership has proven to be one of Kovsies’ areas of expertise. From Wayde van Niekerk making international headlines as the 2015 Men’s 400m World Sprint Champion, to Nicole Walraven who was named as the SA under-21 Hockey 2015 Player of the Year, speaks the language of winners.

Wayde believes that his achievements are also for his family, friends, mentors, and the university community to rejoice in.“What I achieved is our achievement,” he said “the person I am today is because of the people around me.” Also supporting him at this event was MsAns Botha, his coach together with his family and friends.

Andricia Hinckemann’s commitment to promote environmental sustainability in light of the global warming crisis earned her the Miss Earth SA 2015 second princess status.

The UFS Debating Society also joined the ranks as highfliers when announced as South African National Universities Debating Champions for 2015. The UFS team competed in nine preliminary rounds. Devon Watson and NkahisengRalepeli from the UFS had to fight their way through nine preliminary rounds to the finals. Competing in the category English as a First Language, Devon and Nkahiseng brought yet another championship title home.

Success is music to our ears here at Kovsies, Veritas and Marjolein showed us that music can also symbolize success. These residence serenade groups took first and second place, respectively, at the 2015 ATKV National University Sêr competition.

Other students who have the world in their hands and are striving to make it a better place include Rolene Strauss (Miss World 2015), Elzane van der Berg (Deaf Miss South Africa 2014), the Shimlas (2015 Varsity Cup champions),KovsieNetball (2014 Varsity Netball champions and winners of 2014 National Premier League), KovsieTennis (2014 USSA Champions) and Varsity Sevens Champions 2015.

Prof Jonathan Jansen, Vice-Chancellor and Rector of the university remarked upon the inevitable nature of success amongst our university’s students. “Whether they are in athletics, netball, or debating, Kovsie students do well in every aspect of their lives.”

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