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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

Protection of Information bill- opinions from our experts
2011-11-28

Prof. Hussein Solomon
Senior Professor in the Department of Political Science at the University of the Free State. 

In recent years, given their failure to effectively govern, the ANC has become increasingly defensive. These defensive traits have become particularly acute in light of the various corruption scandals that members of the ruling party involve themselves in.
 
Given the fact that for now they are assured of an electoral majority (largely on account of their anti-apartheid credentials), coupled with the fact that they have managed to make parliament a rubber stamp of the executive as opposed to holding the executive accountable, it is the media which has increasingly held the ruling party to account by exposing such corruption and incompetence in government.
 
The passing of the information bill, therefore, is not merely an attack on the media, but an attack on the pivotal issue of accountability. Without accountability, there can be no democracy.
 
By defining national interest broadly, by refusing to accept a public interest clause in the bill, the ANC increasingly shows its disdain to South Africa's constitution and its citizens.
 
More importantly, as former Minister of Intelligence and ANC stalwart Ronnie Kasrils pointedly makes clear, the ANC is also betraying its own noble struggle against the odious apartheid regime. It was the media which played a key role in exposing apartheid's excesses, it is the same media which is coming under attack by the heirs of PW Botha's State Security Council - Minister of State Security Siyabong Cwele and his security apparatchiks whose mindsets reflect more Stalin's Gulag's than the values of the Freedom Charter.
 
The passing of this bill is also taking place at a time when journalists have had their phones attacked, where the judiciary has been deliberately undermined and parliament silenced.
 
Democrats beware!

 
Prof. Johann de Wet
Chairperson: Department of Communication Science 
 
The ANC’s insistence on passing the Protection of State Information Bill in its current form and enforcing it by law, means that the essence of our democratic state and the quality of life of every citizen is at stake.
 
Yes, our freedom as academics, researchers, mass media practitioners and citizens comes into play. Freedom implies the right to choose and is, along with equality, an underlying principle which helps make democracy happen. While the South African state needs to protect (classify) information which could threaten its security and/or survival, the omission of a public interest clause in the Bill at this stage effectively denies a citizen the right to freedom of information.
 
 Freedom of information, along with press freedom, freedom of speech, freedom of assembly, freedom of association and religious freedom, are essential to democracy. These freedoms are granted because they conform to basic liberal ideas associated with (Western) democracy and which resonate with South Africa’s liberal constitution, such as (1) belief in the supreme value of the individual (and thus not of the state); (2) belief that the individual has natural rights (rights which belong to all human beings by nature – such as the right to life and to control government)) which exist independently of government, and which ought to be protected by and against government; and (3) recognition of the supreme value of the individual. 
 
One wonders how many cases of South African government corruption and mismanagement would have been uncovered by investigative journalists over the past number of years if this Bill in its current form was on the statute books. This Bill represents a backward step from the promise of democracy of having an informed public. The former National Party government had similar laws in place and one does not want to go there again. The infamous Information Scandal in South Africa of some thirty years ago, or Muldergate as it has come to be known, reminds one of what governments can do when it works clandestinely.
 
What South Africans need, is more information on what government structures are doing and how they are doing it with taxpayers’ money, not less information. While information in itself does not equal communication or dialogue, it is an indispensable part thereof, and the need for dialogue based on verifiable information is urgent for meeting vexed challenges facing South African communities. Academics in all fields of specialisation are constantly in need of untainted information to pursue answers and/or offer solutions to where South Africa should be moving in all spheres of life.

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