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Obesity / Anti Obesity / Anti Obesity Agents · Journal article
Journal of Ethnopharmacology · July 6, 2026
Encouraging direction, but not yet definitive.
This preclinical study shows that astragalin (ASG), a flavonoid from Morus alba, reduces obesity-related metabolic disturbances in high-fat diet-fed mice through apparent AMPK activation and downstream PI3K/AKT signaling. While the breadth of endpoints and mechanistic convergence are encouraging, the work is in an animal model and does not yet support human use; the authors themselves call for further studies to confirm direct target engagement and downstream signaling.
Preclinical in vivo study in high-fat diet-induced obese mouse model with mechanistic validation. High-fat diet-fed mice with obesity-related metabolic disturbances. Intervention: M. alba aqueous extract or astragalin (ASG). Compared with: HFD-fed control mice (untreated); Compound C co-administration as negative control for AMPK engagement.
M. alba extract significantly reduced body weight gain and improved serum lipid profiles and hepatic lipid accumulation in obese mice ASG recapitulated several beneficial effects of extract, including improvements in body weight gain, glucose tolerance, insulin sensitivity, hepatic lipid burden, and inflammatory status ASG reduced systemic and hepatic pro-inflammatory cytokines and modulated hepatic and intestinal GLUT1/2 transcripts and protein levels
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These findings suggest astragalin warrants further investigation as a potential natural compound for obesity and metabolic dysfunction, but the evidence is preclinical and does not yet support clinical use. Human trials would be needed to establish safety, efficacy, and relevant dosing.
Sound preclinical study in mice demonstrating metabolic benefit of a natural compound via plausible signaling pathways, but lacks human evidence and relies on surrogate endpoints and mechanistic markers rather than clinical outcomes.
As stated by the source record.
Quoted from the source exactly as published.
These findings suggest astragalin warrants further investigation as a potential natural compound for obesity and metabolic dysfunction, but the evidence is preclinical and does not yet support clinical use. Human trials would be needed to establish safety, efficacy, and relevant dosing.
Graded across the dimensions that decide whether you should act, each from what the source actually supports. There is no single score, and where a dimension was not assessed it says so.
Ethnopharmacological relevance. Morus alba L. (M. alba) also known as white mulberry is recognized in traditional Chinese medicine (TCM) and Ayurveda as a functional food and nutraceutical supplement for treating conditions such as hypertension, diabetes, and obesity. In TCM, mulberry leaves are specifically described as enhancing hepatic lipid metabolism, promoting lipid excretion to support obesity treatment.Aim of the study. This study aimed to investigate the anti-obesity potential of M. alba leaf extract and its flavonoid component, astragalin (ASG), using a high-fat diet (HFD)-induced obese mouse model, and to elucidate the underlying molecular mechanisms.Methods. HFD-fed mice were treated with M. alba aqueous extract or ASG using a curative treatment approach. Body weight, glucose tolerance, insulin sensitivity, serum lipid profiles, hepatic steatosis, and inflammatory cytokines were assessed. Systemic and hepatic inflammation was measured by enzyme-linked immunosorbent assay (ELISA), while glucose transporter (GLUT1 and GLUT2) transcripts and protein levels were measured by RT-PCR and Western blotting, respectively. Molecular interactions were evaluated using cellular thermal shift assay (CETSA), drug affinity responsive target stability (DARTS), and molecular docking analyses, while AMP-activated protein kinase (AMPK), phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT), calcium/calmodulin-dependent protein kinase kinase 2 (CaMKK2) and liver kinase B1 (LKB1) phosphorylation was also assessed by Western blotting. Pharmacologic inhibition with Compound C was performed to confirm AMPK involvement.Results. Treatment with M. alba extract significantly reduced body weight gain, improved serum lipid profiles, and attenuated hepatic lipid accumulation in obese mice. Phytochemical analysis identified ASG as a major bioactive constituent. ASG recapitulated several beneficial effects of the extract, including improvements in body weight gain, glucose tolerance, insulin sensitivity, hepatic lipid burden, and inflammatory status. ASG reduced systemic and hepatic levels of pro-inflammatory cytokines and modulated hepatic and intestinal GLUT1/2 transcripts and protein levels. Mechanistically, ASG showed evidence of AMPK engagement in CETSA, DARTS, and docking analyses, and was associated with increased hepatic AMPK and PI3K/AKT phosphorylation. Co-administration of Compound C attenuated several metabolic benefits of ASG, supporting AMPK involvement.Conclusion. ASG ameliorates obesity-related metabolic abnormalities in HFD-fed mice and is associated with AMPK engagement and increased hepatic AMPK/PI3K/AKT phosphorylation. These findings support ASG as a promising natural lead compound for obesity-related metabolic dysfunction, although further studies are needed to define its direct target interaction and downstream signaling more conclusively.
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