Comparative Metabolic, Antioxidant, and Histopathological Effects of Agrimonia pilosa, Calendula arvensis, and Polygonum hydropiper Extracts in Streptozotocin-Induced Diabetic Mice

Background: Oxidative stress, dyslipidemia, weight loss, and tissue injury accompany sustained hyperglycemia and provide complementary endpoints for evaluating botanical interventions. This study compared hydroalcoholic extracts of Agrimonia pilosa, Calendula arvensis, and Polygonum hydropiper with Vaccinium myrtillus as a positive botanical control in a mouse model of streptozotocin-induced diabetes. Methods: Thirty male CD1 mice aged 4–6 weeks were studied in six groups of five animals. Diabetes was induced by a single intraperitoneal administration of streptozotocin at 180 mg/kg body weight. Fasting blood glucose was measured before streptozotocin administration, 72 h and one week after injection. Animals showing fasting blood glucose concentrations >300 mg/dL, confirmed by repeated measurement, were considered diabetic and included in the chronic treatment experiment. Following confirmation of diabetes, hydroalcoholic tinctures were administered orally once daily for 35 days at the previously selected doses: A. pilosa 200 mg/kg, C. arvensis 150 mg/kg, P. hydropiper 100 mg/kg, and V. myrtillus 100 mg/kg as an active botanical comparator. Glycemia and body mass were followed longitudinally; food and water intake were recorded weekly. Whole-blood lipids, malondialdehyde (MDA), total antioxidant capacity (TAC), superoxide dismutase (SOD), glutathione peroxidase (GPx), albumin, and creatinine were assessed, together with histopathology. Animal-level between-group comparisons used two-sided Welch independent-samples t-tests; glycemic treatment-versus-untreated-STZ comparisons were Bonferroni-adjusted. Food and water intake were summarized descriptively because they were recorded at cage level. Results: At day 35, mean glycemia was 358.60 mg/dL in untreated diabetic mice and 122.00, 177.20, 252.20, and 174.80 mg/dL after A. pilosa, P. hydropiper, C. arvensis, and V. myrtillus, respectively. A. pilosa had the lowest glucose mean among survivors, but two animals died, leaving n = 3 at days 28 and 35 and a potential for survivor bias. P. hydropiper showed higher SOD and GPx activities in exploratory pairwise analyses, whereas C. arvensis had the lowest day-35 triglyceride mean. Histopathology revealed hepatic alterations in several treatment groups and myocardial interfascicular edema in P. hydropiper and V. myrtillus; these findings were descriptive and were not used for between-group severity ranking. Conclusions: The extracts showed distinct exploratory activity profiles. P. hydropiper was associated with a numerical glycemic reduction and higher SOD and GPx activities in exploratory pairwise analyses, whereas C. arvensis produced the lowest day-35 triglyceride concentration. A. pilosa showed the largest numerical reduction in glycemia among the surviving animals; however, mortality observed in the A. pilosa group during treatment and the resulting final sample of three animals precluded firm conclusions regarding comparative efficacy.