Evaluation of the Anti-obesity Effects of Alfalfa Aqueous Extract on a High-fat Diet-induced Obesity Model in Rats

Abstract

Background: Obesity is a major metabolic disorder associated with an increased risk of diabetes, cardiovascular disease, and liver damage. Medicinal plants with antioxidant and metabolism-regulating properties may offer a complementary approach to managing obesity-related complications. Objectives: This study aimed to investigate the anti-obesity effects of aqueous alfalfa (Medicago sativa) extract in a high-fat diet-induced obesity model in rats. Methods: In this experimental study, 48 male Wistar rats were randomly assigned to six groups: control, negative control (high-fat diet [HFD]), positive control (HFD + orlistat 5 mg/kg), and three HFD groups receiving alfalfa extract at doses of 200, 400, or 600 mg/kg for 8 weeks. Body weight, fasting blood glucose (FBS), serum glucose, lipid profile (TG, TC, HDL, and LDL), liver enzymes (AST and ALT), and markers of oxidative stress (MDA, SOD, and GSH) were measured. Results: The HFD significantly increased body weight, serum glucose (from 102.83 ± 8.28 to 228.67 ± 35.56 mg/dL), TG (from 54.33 ± 55.70 to 108.33 ± 25.24 mg/dL), total cholesterol (from 56.57 ± 69.40 to 102.83 ± 16.19 mg/dL), LDL (from 28.00 ± 15.42 to 55.17 ± 20.24 mg/dL), ALT (from 25.33 ± 6.50 to 61.80 ± 8.38 U/L), and MDA (from 1.50 ± 0.20 to 4.50 ± 0.40 nmol/mL), while decreasing AST (from 57.00 ± 7.95 to 14.66 ± 1.46 U/L), HDL (from 40.67 ± 20.60 to 26.83 ± 23.43 mg/dL), SOD (from approximately 75.00 ± 8.00 to approximately 18.00 ± 4.00 U/mL), and GSH (from approximately 50.00 ± 5.00 to approximately 20.00 ± 3.00 µmol/L) (P < 0.001 for all). Administration of alfalfa extract at 400 mg/kg significantly improved the reported metabolic and oxidative-stress parameters: glucose decreased to 121.00 ± 12.74 mg/dL, TG to 59.83 ± 12.93 mg/dL, LDL to 27.67 ± 14.43 mg/dL, ALT to 32.83 ± 3.54 U/L, and MDA to 1.80 ± 0.25 nmol/mL, while SOD increased to 55.00 ± 7.00 U/mL and GSH to 45.00 ± 5.50 µmol/L (P < 0.05 vs. HFD for all). Body-weight trajectories differed overall among groups (P < 0.001); however, the time × treatment interaction was not significant (P = 0.081), and the final body weights of all alfalfa-treated groups were higher than those of the negative-control group. The 600 mg/kg dose showed no additional metabolic benefit and was associated with adverse histopathological changes, including persistent lipid vacuoles, inflammatory foci, and occasional hepatocyte necrosis with hemorrhage. Conclusions: Aqueous alfalfa extract at 400 mg/kg demonstrated promising metabolic and antioxidant effects in this animal model of obesity. However, the body-weight findings did not show a definitive treatment-related reduction in weight trajectory, and the adverse effects observed at 600 mg/kg underscore the need for careful safety evaluation. Further toxicological and clinical studies are required before any translational implications can be considered.