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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 offers bursaries for interpreters
2005-12-01

The Unit for Language Management (previously Unit for Language Facilitation and Empowerment) at the University of the Free State (UFS) is offering bursaries to persons who want to apply for the Post-graduate Diploma in Language Practice (interpreting) for 2006. 

The Unit was involved in the setting up of a comprehensive interpreting infrastructure at the Free State Legislature and provided the interpreting services for the Truth and Reconciliation Commission (TRC) for the latter’s full duration.

“The UFS supports a multilingual society.  Our language policy, which was approved by the Council in 2003, is a striking example.  This policy is in accordance with the national movement towards multilingualism and the recognition of language rights.  Through the training of interpreters the UFS is empowering others to exercise their language rights and to partake meaningfully in formal conversations,“ said Prof Theo du Plessis, head of the UFS Unit for Language Management (ULM). 

“The UFS has been using interpreter services at executive management meetings and other occasions such as meetings, seminars and conferences for several years.  The demand for these services has risen quite considerably.  We have found that the current three interpreters on the Main Campus will soon not be able to cope with this demand,” said Prof du Plessis.

According to Prof du Plessis institutions like the Mangaung Local Municipality and the Motheo District Municipality use the interpreter services of the ULM on a regular basis. 
“Because the demand for interpreter services is becoming so great, the demand for trained interpreters is also increasing.  This is why we are offering bursaries for persons who want to be trained as interpreters to register in 2006 for the Post-graduate Diploma in Language Practice (interpreting) as offered by the UFS Department of Afro-asiatic Studies and Language Practice and Sign Language,” said Prof du Plessis.

According to Prof du Plessis the UFS will be able to use these students on an ad-hoc basis to assist with interpreter services on the Main Campus or to deliver interpreter services to institutions outside the UFS. 

The bursaries will preferably be awarded to persons with English as mother tongue with an above average knowledge of Afrikaans or Sesotho.  The duration of the bursaries is one year and only tuition fees will be paid.  “To qualify for the bursaries, prospective students must have an undergraduate qualification,” said Prof du Plessis.

The closing date for applications is 25 January 2006.  For any enquiries, Mrs Susan Lombaard can be contacted at (051) 401-2405 or 072 605 4966 during office hours or at lombasc.hum@mail.uovs.ac.za.

Media release
Issued by: Lacea Loader
Media Representative
Tel:  (051) 401-2584
Cell:  083 645 2454
E-mail:  loaderl.stg@mail.uovs.ac.za
1 December 2005
 

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