Dose-dependent antidiabetic and multiorgan protective effects of Ziziphus abyssinica methanolic extract in streptozotocin-induced diabetic mice

Abstract

BACKGROUND: Diabetes mellitus (DM) is a global health challenge, with rising prevalence and significant economic burden, particularly in low- and middle-income countries. Current synthetic antidiabetic drugs, though effective, are associated with adverse effects, prompting interest in plant-based alternatives. OBJECTIVES: This study evaluated the antidiabetic potential of Ziziphus abyssinica methanolic extract (ZAE) in streptozotocin (STZ)-induced diabetic mice. METHODS: Male Swiss Albino mice were grouped into normal control, diabetic control, glibenclamide (5 mg/kg), and ZAE-treated (200, 400, 600 mg/kg) groups. Parameters were monitored for 28 days. RESULTS: ZAE at 600 mg/kg normalized blood glucose (148.7 ± 11.0 mg/dL vs. normal control group 148.0 ± 3.0 mg/dL, ∗P∗ >0.05), achieving a 66 % reduction (∗P ∗ < 0.001) versus diabetic controls (437.2 ± 43.6 mg/dL). Body weight recovered fully (40.5 ± 1.9 g vs. 41.2 ± 1.2 g, ∗P ∗ >0.05), contrasting with a 25 % loss in diabetic controls (∗P∗ < 0.001). Lipid profiles improved, with HDL rising (61.8 ± 3.9 vs. 33 ± 2.4 mg/dL, ∗P∗ = 0.002) and LDL declining (37.5 ± 2.4 vs. 58.8 ± 3.7 mg/dL, ∗P∗ = 0.002). Liver (ALT, AST, ALP) and renal (creatinine, urea) markers normalized (∗P∗ < 0.05). Histopathology revealed β-cell preservation (∗P∗ < 0.01) and, specifically at the 600 mg/kg, a marked reduction in hepatic inflammation and renal protection. CONCLUSION: The 600 mg/kg ZAE demonstrated novel, dose-dependent efficacy not only in glycemic control but also in pancreatic β-cell preservation and multiorgan protection, showing significant benefits in renal and cardiac tissues where glibenclamide was ineffective. These findings suggest the traditional use of Ziziphus abyssinica and highlight the potential of 600 mg/kg regimen to provide concurrent glycemic control and multi-organ protection.