Impact of Allium ursinum Extract on the Metabolism of Diabetic Mice: An NMR-Based Approach to Uncover Glucose-Regulating Mechanisms

Introduction: Allium ursinum (A. ursinum) is a medicinal plant recognized for its wide range of therapeutic properties, including anti-inflammatory, antioxidant, and antidiabetic activities. Nevertheless, the precise metabolic mechanisms underlying antidiabetic effects remain insufficiently understood. In this study, we aimed to investigate the hypoglycemic effects of A. ursinum hydro-methanolic extract and characterize the associated metabolic changes in diabetic Balb/C mice. Materials and Methods: Hydro-methanolic extract of A. ursinum was prepared, and then its polar and volatile constituents were identified using Liquid Chromatography-Mass Spectrometry and Gas Chromatography-Mass Spectrometry, respectively. Forty mice were allocated into control groups (healthy, diabetic + solvent, and diabetic + metformin) and experimental groups receiving different doses of A. ursinum extract. Treatments were administered for ۲۱ consecutive days, after which blood glucose levels were assessed, and the effective doses (ED۵۰ and ED۹۰) were calculated. To assess metabolic changes associated with the hypoglycemic effects, serum samples were analyzed using proton nuclear magnetic resonance (۱H-NMR)-based metabolomics. Hepatic and renal toxicity were evaluated by enzymatic assay and histopathological examinations. Results: The administration of A. ursinum at tested doses led to a significant decrease in blood glucose levels in diabetic mice (۱۶۰ mg/kg). These hypoglycemic effects were accompanied by notable changes in the serum metabolic profile, affecting pathways such as ketone body synthesis and degradation, D-glutamate metabolism, pyruvate metabolism, glycolysis/gluconeogenesis, arginine biosynthesis, and the tricarboxylic acid cycle. Importantly, no evidence of liver or kidney toxicity was observed at the higher dose (ED۹۰ = ۱۴۱ mg/kg). Conclusions: This study showed that A. ursinum has antidiabetic effects and highlighted the role of metabolite changes in diabetes pathophysiology. Hence, the glucose-lowering metabolites identified could be potential targets for the development of future antidiabetic treatments.

کلیدواژه ها:

plant extract ، Allium ursinum ، Metabolomics ، Diabetes ، Hypoglycemic ، Tissue Toxicity