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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

Media: ANC can learn a lesson from Moshoeshoe
2006-05-20


27/05/2006 20:32 - (SA) 
ANC can learn a lesson from Moshoeshoe
ON 2004, the University of the Free State turned 100 years old. As part of its centenary celebrations, the idea of the Moshoeshoe Memorial Lecture was mooted as part of another idea: to promote the study of the meaning of Moshoeshoe.

This lecture comes at a critical point in South Africa's still-new democracy. There are indications that the value of public engagement that Moshoeshoe prized highly through his lipitso [community gatherings], and now also a prized feature in our democracy, may be under serious threat. It is for this reason that I would like to dedicate this lecture to all those in our country and elsewhere who daily or weekly, or however frequently, have had the courage to express their considered opinions on pressing matters facing our society. They may be columnists, editors, commentators, artists of all kinds, academics and writers of letters to the editor, non-violent protesters with their placards and cartoonists who put a mirror in front of our eyes.

There is a remarkable story of how Moshoeshoe dealt with Mzilikazi, the aggressor who attacked Thaba Bosiu and failed. So when Mzilikazi retreated from Thaba Bosiu with a bruised ego after failing to take over the mountain, Moshoeshoe, in an unexpected turn of events, sent him cattle to return home bruised but grateful for the generosity of a victorious target of his aggression. At least he would not starve along the way. It was a devastating act of magnanimity which signalled a phenomenal role change.

"If only you had asked," Moshoeshoe seemed to be saying, "I could have given you some cattle. Have them anyway."

It was impossible for Mzilikazi not to have felt ashamed. At the same time, he could still present himself to his people as one who was so feared that even in defeat he was given cattle. At any rate, he never returned.

I look at our situation in South Africa and find that the wisdom of Moshoeshoe's method produced one of the defining moments that led to South Africa's momentous transition to democracy. Part of Nelson Mandela's legacy is precisely this: what I have called counter-intuitive leadership and the immense possibilities it offers for re-imagining whole societies.

A number of events in the past 12 months have made me wonder whether we are faced with a new situation that may have arisen. An increasing number of highly intelligent, sensitive and highly committed South Africans across the class, racial and cultural spectrum confess to feeling uncertain and vulnerable as never before since 1994. When indomitable optimists confess to having a sense of things unhinging, the misery of anxiety spreads. It must have something to do with an accumulation of events that convey the sense of impending implosion. It is the sense that events are spiralling out of control and no one among the leadership of the country seems to have a handle on things.

I should mention the one event that has dominated the national scene continuously for many months now. It is, of course, the trying events around the recent trial and acquittal of Jacob Zuma. The aftermath continues to dominate the news and public discourse. What, really, have we learnt or are learning from it all? It is probably too early to tell. Yet the drama seems far from over, promising to keep us all without relief, and in a state of anguish. It seems poised to reveal more faultlines in our national life than answers and solutions.

We need a mechanism that will affirm the different positions of the contestants validating their honesty in a way that will give the public confidence that real solutions are possible. It is this kind of openness, which never comes easily, that leads to breakthrough solutions, of the kind Moshoeshoe's wisdom symbolises.

Who will take this courageous step? What is clear is that a complex democracy like South Africa's cannot survive a single authority. Only multiple authorities within a constitutional framework have a real chance. I want to press this matter further.

Could it be that part of the problem is that we are unable to deal with the notion of "opposition". We are horrified that any of us could become "the opposition". In reality, it is time we began to anticipate the arrival of a moment when there was no longer a single [overwhelmingly] dominant political force as is currently the case. Such is the course of change. The measure of the maturity of the current political environment will be in how it can create conditions that anticipate that moment rather than ones that seek to prevent it. This is the formidable challenge of a popular post-apartheid political movement.

Can it conceptually anticipate a future when it is no longer overwhelmingly in control, in the form in which it currently is and resist, counter-intuitively, the temptation to prevent such an eventuality? Successfully resisting such an option would enable its current vision and its ultimate legacy to our country to manifest itself in different articulations of itself, which then contend for social influence.

In this way, the vision never really dies, it simply evolves into higher, more complex forms of itself. If the resulting versions are what is called "the opposition" that should not be such a bad thing - unless we want to invent another name for it. The image of flying ants going off to start other similar settlements is not so inappropriate.

I do not wish to suggest that the nuptial flights of the alliance partners are about to occur: only that it is a mark of leadership foresight to anticipate them conceptually. Any political movement that has visions of itself as a perpetual entity should look at the compelling evidence of history. Few have survived those defining moments when they should have been more elastic, and that because they were not, did not live to see the next day.

I believe we may have reached a moment not fundamentally different from the sobering, yet uplifting and vision-making, nation-building realities that led to Kempton Park in the early 1990s. The difference between then and now is that the black majority is not facing white compatriots across the negotiating table. Rather, it is facing itself: perhaps really for the first time since 1994. It is not a time for repeating old platitudes. Could we apply to ourselves the same degree of inventiveness and rigorous negotiation we displayed up to the adoption or our Constitution?

Morena Moshoeshoe faced similarly formative challenges. He seems to have been a great listener. No problem was too insignificant that it could not be addressed. He seems to have networked actively across the spectrum of society. He seems to have kept a close eye on the world beyond Lesotho, forming strong friendships and alliances, weighing his options constantly. He seems to have had patience and forbearance. He had tons of data before him before he could propose the unexpected. He tells us across the years that moments of renewal demand no less.

  • This is an editied version of the inaugural Moshoeshoe Memorial Lecture presented by Univeristy of Cape Town vice-chancellor Professor Ndebele at the University of the Free State on Thursday. Perspectives on Leadership Challenges In South Africa

 

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