SYNERGISTIC ANTIDIABETIC EFFECTS OF BERBERIS ARISTATA AND HAMELIA PATENS EXTRACTS IN HIGH-FAT DIET/STREPTOZOTOCIN-INDUCED TYPE 2 DIABETIC RATS: BIOCHEMICAL, HISTOPATHOLOGICAL, AND PHYTOCHEMICAL INVESTIGATIONS

Abstract

Type 2 diabetes mellitus (T2DM) is a progressive metabolic disorder marked by chronic hyperglycemia, insulin resistance, oxidative stress, and pancreatic β-cell dysfunction. Although conventional antidiabetic drugs improve glycemic control, long-term use can cause adverse effects, underscoring the need for safer, multitarget therapies. Berberis aristata and Hamelia patens have antihyperglycemic and antioxidant properties; however, their combined efficacy remains underexplored. This study investigated the synergistic antidiabetic effects of combined extracts of B. aristata and H. patens in an HFD/STZ-induced diabetic rat model. Thirty-six Wistar rats were divided into six groups (n = 6). Diabetes was induced with HFD followed by streptozotocin (50 mg/kg, i.p.). Diabetic rats received gliclazide (10 mg/kg), B. aristata (100 mg/kg), H. patens (100 mg/kg), or their combination (200 mg/kg) orally for six weeks. Body weight, fasting blood glucose, HbA1c, lipid profile, renal biomarkers, urinary parameters, phytochemicals, and pancreatic histopathology were evaluated. The combined extract showed superior antidiabetic activity compared with the individual extracts, significantly improving glycemic control, body weight, lipid profile, and renal function. Fasting blood glucose decreased from 339.0 ± 1.63 to 267.8 ± 2.27 mg/dL, whereas diabetic controls remained hyperglycemic (357.0 ± 1.73 mg/dL). The combination normalized fasting glucose (91.6 mg/dL) and HbA1c (4.6%), improved blood urea (20.36 mg/dL) and creatinine (0.66 mg/dL), eliminated urinary glucose, and restored pancreatic islet architecture with marked β-cell preservation. Overall, the combination exhibited significant synergistic antidiabetic effects and represents a promising polyherbal therapeutic candidate for T2DM management.