The research team of Dr Xavier Wong Hoi-leong, Associate Professor (left), and Dr Pallavi Asthana, Research Assistant Professor (right) of the School of Chinese Medicine at HKBU demonstrated for the first time that artesunate is able to treat obesity in a non-human primate.

The research findings have been published in the international academic journal Nature Communications.

Artesunate as an anti-obesity agent

The treatment of obesity typically involves a combination of lifestyle changes and medications. However, patient compliance with exercise and dietary changes is often challenging, and many anti-obesity drugs are associated with adverse effects. Artesunate is an FDA-approved anti-malaria drug. Previous studies have unveiled another beneficial effect of artesunate in reducing body weight in obese mice, but the mechanism of how this is achieved is unclear.

A research team led by scholars at HKBU's School of Chinese Medicine (SCM) including Dr Xavier Wong Hoi-leong, Associate Professor; Professor Bian Zhaoxiang, Chair Professor and Tsang Shiu Tim Endowed Professor in Chinese Medicine Clinical Studies; and Dr Pallavi Asthana, Research Assistant Professor, discovered that artesunate is a powerful anti-obesity agent using computer simulated-drug screening methods. They also examined the effects of artesunate treatment in animal models with obesity and investigated its impact on a hormone that regulates bodyweight and appetite.

Body fat reduction of 30% in mice model

The researchers explored the therapeutic effect of artesunate on obesity using mice with diet-induced obesity. Daily administration of artesunate to the obese mice over a period of 13 days led to a reduction in average body weight of approximately 10%, and a dramatic reduction in average body fat of approximately 30%, which was attributable to reduced food intake.

Compared to other commercially available weight loss drugs like metformin and liraglutide, artesunate has been found to be more effective in regulating body weight as well as controlling food intake, improving insulin sensitivity, reducing fat, lowering cholesterol levels in the blood, and alleviating fatty liver disease in obese mice.

Demonstrates anti-obesity effect in primate

To further investigate artesunate's potential as an anti-obesity agent for humans, the researchers conducted an experiment using macaques, a non-human primate. They injected artesunate into obese macaques every two days for two weeks. The macaques showed a drop in the total food intake during the period and consumed approximately 25% less food compared to a control group without artesunate injection.

Throughout the study, the artesunate-treated macaques showed approximately 7% reduction in body weight without obvious weight rebound upon treatment discontinuation. Their fasting insulin and blood glucose levels were also lower, indicating improved insulin sensitivity.

In addition, there were no negative effects on the kidneys of the obese macaques due to artesunate treatment. Regular blood tests showed significant improvements in liver and metabolic health. More importantly, the treated macaques did not show any signs of nausea and malaise. The results highlight the potential of artesunate as an effective and safe anti-obesity agent for humans.

Dr Wong said: "Unlike many anti-obesity drugs with varying degrees of adverse effects, artesunate has been used as a potent anti-malarial drug with a good profile of safety and efficacy for decades. Given the strong anti-obesity effects of artesunate demonstrated by the results of our experiments using a primate model, it is suggested that artesunate can be repurposed as an effective therapeutic agent for the treatment of human obesity, which may bring better treatment results for obese patients."

Triggers signal to reduce food intake

The researchers further unveiled the mechanism of how artesunate controls bodyweight and appetite. It was discovered that artesunate increases circulating levels of Growth Differentiation Factor 15 (GDF15), an appetite-regulating hormone which is secreted by various tissues in the body. When GDF15 binds to and activates the receptor named the GDNF family receptor α-like (GFRAL), it triggers a signal from the hindbrain to reduce food intake.

Professor Bian said: "Our study described the signalling mechanism of how artesunate reduces food intake and body weight, which lays the foundation of further investigation on this compound as a potential anti-obesity agent. However, a series of studies and trials on its efficacy, safety and other aspects of application on humans are needed before it can be deployed properly for the purpose of obesity treatment.

"The research results provide hope for developing a novel treatment agent in response to the public health challenge of obesity, which warrants more extensive and effective interventions," he added.

SOURCE Hong Kong Baptist University