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SA plant extracts and zebrafish larvae could hold key to better epilepsy medication

20 September 2024 | Story André Damons | Photo Supplied

zebrafish-blue-in-aquarium — 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.”

The Noldus Daniovision equipment used by Prof Anke Wilhelm.

News Archive

Conference: Expanded ARV treatment

2005-03-02

VENUE: University of the Free State, Bloemfontein, South Africa
DATE: 30 March 2005 - 1 April 2005

ARV Programme as on 24Feb Download Word document
Programme Special events Download Word document

Official web site www.fshealth.gov.za/subsites/arvc

Rationale for the Conference
At the time of the planned Conference, much ground would have been covered, both in the Free State and in South Africa, in respect of the expanded public sector ARV treatment programme in respect of research, experiences in practice, training of staff, treatment of patients, lessons learned, successes and failures, etc. The time would then be quite opportune to share these in a systematic manner with other provinces and countries, as well as with the large variety of stakeholders and role players in the ARV and related domains, be they academics and researchers, policy makers and service/facility managers, the variety of caregivers, and the community organisations and affected patients.

The Conference and current research
The proposed Conference is, firstly, directly linked to the current research on the public sector roll-out of ARV treatment in the Free State conducted by several research institutions (e.g. CIET, CHSR&D, UCT Lung Institute). Secondly, the Conference could and would serve as a forum for other research groups in the country and further a field to report and share knowledge and experiences on ARV treatment and related initiatives. Lastly, the Conference will stage a golden opportunity for researchers and scientists, on the one hand, and policy makers, managers, and caregivers (as knowledge users), on the other hand, to engage in cross-disciplinary discourse on this mutual and topical theme.

Theme of Conference
Expanded ARV treatment in the Free State: sharing experiences

Focus
The focus is primarily on public sector ARV treatment in the Free State, but also initiatives/activities/perspectives of relevance to the Free State elsewhere in the country at large and further a field, as well as relevant ARV initiatives in the public, private, NGO and FBO sectors. Bear in mind, however, that ARV treatment is but part of a much more comprehensive approach to HIV and AIDS. The Conference will, therefore, not narrowly focus on the ARV treatment programme only. The broader context, other relevant dimensions, and a comprehensive approach to the challenges of HIV, AIDS and TB are of equal importance.

The purpose of the Conference
Enhance meaningful exchange, mutual understanding and collaboration among researchers, scientists, policy makers, managers and practitioners in the field of ARV treatment and related fields.

Share experiences in the various spheres of ARV treatment and related spheres (policy, management, practice, research, training, public-private-civil society sectors).

Record, reflect and report on the establishment of the ARV treatment programme in the Free State, and in within the context of the comprehensive HIV/AIDS programme.

Disseminate important research results on ARV treatment and related themes to health policy makers, managers, practitioners, communities and to the research community.

Stimulate discourse among various disciplines and various stakeholders/role players involved in ARV treatment and related programmes.

Sensitise and acquaint researchers to the requirements of policy makers, managers and practitioners in respect of ARV treatment and related fields.

Facilitate the implementation of research results in ARV treatment policy, programmes and practice.

Dissemination of Conference-related information
Information generated during the Conference could feed into policy, management and practice of ARV treatment, the training accompanying such programme, and the existing body of knowledge. After the Conference the information will be disseminated via the Internet and by scientific and popular publications.

Date and duration
Set for 30 & 31 March & 1 April 2005; to commence at 09:00 on the first day (30 March) and to end at 16:30 (1 April) the third day.

Format and scope of Conference
Alternating plenary, parallel sessions and debates focused on topical issues and interest groups. The Conference will strive to be maximally interactive and participative.

Themes and topics to cover:

Policy, management and health services/practice (various levels and contexts – clinical treatment, information, IT systems, pharmacy, laboratories, nutrition)
Research covering all relevant disciplines and diverse dimensions of ARV treatment and related themes
Training and evaluation of training
Patients, communities and civil society organisations
Public, private, NGO, FBO initiatives and partnerships

Emphasis will be on the Free State, however, with of significant involvement from other provinces, SADC countries, and countries further a field. The thrust will be to export lessons and experiences from the Free State, but also to import lessons and experiences from other provinces, countries and sectors.

Presenters
Key presenters from the Free State, other provinces, South Africa, from the private, FBO and NGO sectors, and from several other countries

Delegates
About half of the delegates will be Free State stakeholders and role players (all levels and all contexts). The other half will be role players and stakeholders in the ARV and related fields from other provinces, the national level, and other countries, as well as from the private, public and non-governmental sectors.

Focused workshops
Provision will be made for half-a-day or one-day workshop initiatives on the third day (1 April 2005).

Enquiries
For more information please contact:

Prof Dingie van Rensburg
Centre for Health Systems Research & Development
University of the Free State
PO Box 339
Bloenfontein
SOUTH AFRICA
9300

Contact:
Carin van Vuuren
Conference Organiser
Centre for Health Systems Research & Development
University of the Free State
P.O.Box 339
Bloemfontein
South Africa
9300
Tel +27 (0) 51 401 2181
Fax +27 (0) 51 4480370
Cell 0832932890
e-mail: arvconference.hum@mail.uovs.ac.za

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