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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 appoints first black woman director
2006-05-03

 The Executive Management of the University of the Free State’s (UFS) has approved the appointment of Mrs Refiloe Seane as Director of Kovsie Student Counselling, and Dr Francois Strydom as Director of Student Development. 

Ms Seane is the first black woman director to be appointed at the UFS and has been acting in this position since last year.

“Mrs Seane’s appointment is the latest in a series of appointments of women in management positions at the UFS.  It signifies our commitment to create a diverse and dynamic institution of higher learning,” said Prof Frederick Fourie, Rector and Vice-Chancellor of the UFS.

Other appointments of women in management positions include that of Prof Magda Fourie as Vice-Rector:  Academic Planning; Prof Letticia Moja as Dean: Faculty of Health Sciences; Dr Choice Makhetha as Vice-Dean:  Student Affairs and Prof Engela Pretorius as Vice-Dean: Humanities. 

Mrs Seane joined the UFS in 1997 as counselling psychologist at Kovsie Counselling.  In 2003 she was promoted to senior psychologist. She holds a master’s degree in Counselling Psychology at the UFS.

“The need for students to receive counselling is steadily on the increase.  I contribute this to the increasing challenges facing young people of today.  Some of the issues we deal with include among others personal adjustment to the university environment, learning and study skills, career guidance and developmental and psychological problems,” said Mrs Seane.

“I commit myself to develop students and prepare them for their studies and careers ahead. My aim is to improve the efficiency of counselling services at the UFS.  This will help produce balanced graduates who will become role players both nationally and internationally,” said Mrs Seane.

Dr Francois Strydom has been appointed as Head/Director for Kovsie Student Development.  Before his appointment Dr Strydom was senior lecturer at the University of the Witwatersrand’s (WITS) School of Human and Community Development.  He holds a Ph D in Psychology from Oxford University, after having obtained a BA degree, BA Honours and master’s degrees in Psychology at the UFS.

“This appointment signals the elevation of the function of student development to directorate level for the first time. It reflects the commitment of the University to support students and their academic development in order to improve their academic success rates. The increase of success rates of especially black students from disadvantaged school backgrounds is a key element of the transformation process of the UFS,” said Prof Fourie.

Media Release
Issued by: Lacea Loader
Media Representative
Tel:  (051) 401-2584
Cell:  083 645 2454
E-mail:  loaderl.stg@mail.uovs.ac.za
2 May 2006

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