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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 on energy-saving mode
2009-09-15

The University of the Free State (UFS) has undertaken several measures to reduce energy consumption on the Main Campus in Bloemfontein.

“Part of Eskom’s strategy is that all the main universities must reduce their electricity consumption. Because the university is the second biggest user of electricity in Bloemfontein we have to cut our consumption according to the new energy policy,” said Prof. Niel Viljoen, Chief Director of Operations at the UFS.

“Electricity is also expensive and if we look at global warming and everybody’s responsibility, I think we all have a moral obligation to save energy,” said Prof. Viljoen.

“The energy crisis of January 2008 and beyond, with its load-shedding limitations, was a major driver for the government to introduce the Power Conservation Scheme,” said Mr Anton Calitz, the UFS’s electrical engineer.

The measures put in place by the UFS include amongst others:

The introduction of a solar water-heating system in the residences, which is a first of its kind in Bloemfontein.
An investigation is also being launched into alternatives and the effective heating of rooms in the residences.

Feasibility studies are currently being conducted to determine whether energy saving can be achieved with radiation panels.

Energy-saving lights have been installed in the following buildings: the Architecture Building, Genmin Lectorium, Geology lecture halls, Winkie Direko Building, George du Toit Building, Sasol Library, Francois Retief Building, as well as in the residences. This measure has resulted in massive energy saving.

Energy meters for the Library, Computer Laboratory Building, François Retief Building and Steyn Substation are being planned as the first phase.

Real-time metering will result in every UFS computer user being aware of power consumption on the campus.

New lift motors and control systems that reduce energy consumption have been installed at the Agriculture and the George du Toit Buildings.

In the Computer Laboratory Building the temperature adjusting point for the venues is set at 22 °C and, in the case of new projects, green guidelines are applied.

It is expected that the government and local authorities will bring more pressure to bear on the UFS to save energy. Applications for increased capacity will possibly be linked to energy-saving targets.

This trend will continue until 2014 when additional power stations will be put into operation.

“Our aim is to save 10% on energy consumption,” said Prof. Viljoen.

“Heavy financial penalties will be imposed if a 10% saving is not achieved,” added Mr Calitz.

On average, our energy consumption per day this year is 128,964 kWh as compared to last year’s 119,752 kWh.

Media Release
Issued by: Mangaliso Radebe
Assistant Director: Media Liaison
Tel: 051 401 2828
Cell: 078 460 3320
E-mail: radebemt.stg@ufs.ac.za  
14 September 2009

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