Halofuginone shows promise for weight loss by boosting key metabolic regulators.
Overweight and obesity have quickly become major global health challenges, increasing the risk for a wide range of serious diseases. As people around the world strive for healthier lifestyles, the demand for effective weight loss solutions is growing stronger than ever. Halofuginone (HF), a natural compound extracted from the roots and leaves of the Changshan plant, could emerge as a powerful new option for tackling obesity.
For more than 2,000 years, Changshan, the root of Dichroa febrifuga Lour, has been used in traditional Chinese medicine to treat fever caused by malaria. While its healing properties have been known for centuries, scientists have only recently started to explore whether HF might also help address modern health concerns like obesity and its related complications.
In an important breakthrough, a research team led by Professor Jianping Weng from the University of Science and Technology of China (USTC), working closely with Academician John R. Speakman from the Shenzhen Institutes of Advanced Technology, found that HF can do much more than previously thought.
Their study, published in Science Advances, revealed that HF boosts levels of two critical proteins: growth differentiation factor 15 (GDF15) and fibroblast growth factor 21 (FGF21). These proteins play key roles in controlling appetite and regulating metabolism, leading to reduced body weight and better overall metabolic health.
In a preclinical mouse experiment, researchers accidentally discovered that HF could safely reduce weight, and further studied its weight reduction effect in a diet-induced obese (DIO) animal model.
Mechanisms Behind Weight Reduction
The study found that GDF15, the so called “anorexigenic factor”, which reduced food intake and achieved weight loss by acting on the GDNF family receptor α-like (GFRAL) receptor in the brain.
FGF21, as a core metabolic hormone secreted by the liver, can promote energy consumption, enhance insulin sensitivity, and regulate metabolism in the liver and adipose tissue.
The secret of how HF achieved significant weight management effects lay in its increasing of endogenous GDF15 and FGF21, thereby reducing appetite and increasing energy expenditure in a dual approach. Compared to GDF15 and FGF21 recombinant protein drugs, upregulating GDF15 and FGF21 levels through small molecule drugs are more economical and of patient compliance.
Consistent Metabolic Benefits
In a DIO mouse model, researchers observed a significant decrease in body weight and enhanced energy metabolism (FGF21 promotes fat burning), as well as improved insulin sensitivity.
These metabolic benefits of HF were maintained regardless of the sex of the mouse, the method of administration, the type of animal model (DIO mice, ob/ob mice, DIO minipigs) and the feeding temperature.
The researchers further pointed out that HF up-regulated the expression and secretion of GDF15 and FGF21 through integrating stress response. Knocking down GDF15 and FGF21, respectively, can partially offset the weight loss mediated by HF. HF, as an EPRS1 inhibitor, can exert the effect of reducing weight.
However, MAZ-negative compounds, which are unable to inhibit EPRS1, could not reduce weight and did not have the ability to upregulate GDF15 and FGF21, implying that EPRS1 may be the direct molecular target of HF for weight loss.
The study suggests that HF and its chemical derivatives hold promise as potential new drugs for treating the obesity. From antimalarial to anti-obesity, the cross-disciplinary preclinical use of HF, once again, underlines the significance of the traditional Chinese medicine in modern drug research and development.
Reference: “The clinical antiprotozoal drug halofuginone promotes weight loss by elevating GDF15 and FGF21” by Suowen Xu, Zhenghong Liu, Tian Tian, Wenqi Zhao, Zhihua Wang, Monan Liu, Mengyun Xu, Fanshun Zhang, Zhidan Zhang, Meijie Chen, Yanjun Yin, Meiming Su, Wenxiang Fang, Wenhao Pan, Shiyong Liu, Min-dian Li, Peter J. Little, Danielle Kamato, Songyang Zhang, Dongdong Wang, Stefan Offermanns, John R. Speakman and Jianping Weng, 26 March 2025, Science Advances.
DOI: 10.1126/sciadv.adt3142
Never miss a breakthrough: Join the SciTechDaily newsletter.
Follow us on Google and Google News.
2 Comments
How do I get the HF product
Google is your friend:
Recent research suggests that a compound found in the herbal medicine Changshan (Dichroa febrifuga), traditionally used for malaria-induced fever for over 2,000 years, may be a new option for treating obesity.
Specifically, Halofuginone (HF), an alkaloid in Changshan, has shown potential in regulating appetite and energy metabolism by increasing the levels of certain proteins (GDF15 and FGF21) that play key roles in appetite control and metabolism.