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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

SA must appoint competent judges
2009-05-08

 

At the inaugural lecture are, from the left: Prof. Teuns Verschoor, Acting Rector of the UFS, Judge Farlam and Prof. Johan Henning, Dean of the Faculty of Law at the UFS.

Supreme Court of Appeal Judge Ian Farlam has called on the South African government to appoint and continue to appoint competent, fair and experienced judicial officers to sit in the country’s courts.

He also emphasised the need to have an efficient and highly respected appellate division, which rightly enjoys the confidence of all.

Judge Farlam was speaking at the University of the Free State (UFS) where he delivered his inaugural lecture as Extraordinary Professor in Roman Law, Legal History and Comparative Law in the Faculty of Law.

He said there were important lessons that emanated from the study of legal history in the Free State, particularly including the lesson that there were courageous jurists who spoke up for what they believed to be right, and a legislature who listened and did the right thing when required.

“This is part of our South African heritage which is largely forgotten – even by those whose predecessors were directly responsible for it. It is something which they and the rest of us can remember with pride,” Judge Farlam said.

Addressing the topic, Cox and Constitutionalism: Aspects of Free State Legal History, Judge Farlam used the murder trial of Charles Cox, who was accused of killing his wife and both daughters, to illustrate several key points of legal history.

Cox was eventually found guilty and executed, however, the trial caused a deep rift between the Afrikaans and English speaking communities in the Free State.

Judge Farlam also emphasised that the Free State Constitution embodied the principle of constitutionalism, with the result that the Free State was a state where the Constitution and not the legislature was sovereign. He said it was unfortunate that this valuable principle was eliminated in the Free State after the Boer War and said that it took 94 years before it was reinstated.

Judge Farlam added, “Who knows what suffering and tragedy might not have been avoided if, instead of the Westminster system, which was patently unsuited to South African conditions, we had gone into Union in 1910 with what one can describe as the better Trekker tradition, the tradition of constitutionalism that the wise burghers of the Free State chose in 1854 to take over into their Constitution from what we would call today the constitutional best practice of their time?”

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
8 May 2009
             

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