Integrative Therapy with Moringa o leifera Leaf Extract and Sitagliptin Potentiates Antidiabetic, Antidyslipidemic, and Hepatoprotective Effects in Streptozotocin-Induced Diabetic Rats

Abstract

Introduction : In diabetics, hyperglycemia leads to dyslipidemia and liver damage. Integrative therapy combining traditional medicine with a conventional antidiabetic drug is an innovative strategy to alleviate these issues with a lower dose and fewer adverse effects. Therefore, we investigated the antidiabetic, antidyslipidemic, and hepatoprotective effects of Moringa oleifera leaf extract, alone and in combination with sitagliptin, at a comparatively lower dose in streptozotocin-induced diabetic rats. Methods : Thirty (30) Swiss albino male rats were allocated into five groups. Except for the normal control group, diabetes was induced using a single dose of streptozotocin (STZ, 45 mg/kg, intraperitoneally). Over a 4-week experimental period, the effects of SGT (Sitagliptin, 100 mg/70 kg BW), MoLE ( Moringa oleifera leaves extract, 200 mg/kg BW), and SGT + MoLE (integrative therapy of sitagliptin, 50 mg/70 kg BW with ethanolic M. oleifera leaves extract, 100 mg/kg BW) were evaluated. The study assessed blood glucose, glycosylated hemoglobin (HbA1c), serum lipid profile, triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-c), and low-density lipoprotein cholesterol (LDL-c) and liver function markers such as protein level (albumin, globulin) and serum enzymes, alanine transaminase (ALT) and aspartate transaminase (AST), alkaline phosphatase (ALP) and gamma-glutamyl transferase (GGT). Results and Discussion : The SGT, MoLE, and SGT + MoLE groups showed a significant reduction (p < 0.05) in plasma glucose ((5.98 ± 0.44) mmol/L, (6.10 ± 0.50) mmol/L and (5.74 ± 0.53) mmol/L, respectively) compared to diabetic control ((13.76 ± 0.83) mmol/L) as well as HbA1c levels (4.70% ± 0.48%, 5.24% ± 0.67% and 4.30% ± 0.23%, respectively) compared to diabetic control rats (9.38% ± 0.54%) after 4 weeks of treatment. Diabetics rats treated with SGT, MoLE, and SGT + MoLE significantly attenuated the elevation of total cholesterol ((102.9 ± 7.09) mg/dL vs (88.48 ± 6.354) mg/dL, (90.38 ± 6.419) mg/dL and (81.24 ± 5.767) mg/dL, respectively; diabetics vs SGT, MoLE, and SGT + MoLE treated group), triglycerides ((83.22 ± 7.75) mg/dL vs (72.08 ± 5.40) mg/dL, (75.24 ± 5.29) mg/dL and (70.84 ± 6.80) mg/dL, respectively), LDL cholesterol ((78.12 ± 6.98) mg/dL vs (58.90 ± 6.20) mg/dL, (61.96 ± 6.05) mg/dL and (60.26 ± 7.42) mg/dL, respectively), while attenuated reduced level of HDL cholesterol ((29.48 ± 3.59) vs (39.94 ± 4.05) mg/dL, (37.68 ± 4.54) mg/dL and (40.10 ± 5.89) mg/dL, respectively). Albumin levels decreased while globulin levels increased in diabetic rats; after treatment, both were restored to normal. Rats with diabetes had significantly higher levels of the liver enzymes ALT, AST, ALP, and GGT. The treatment of SGT, MoLE, and SGT + MoLE significantly attenuated these increased enzyme levels, but M . oleifera extract alone did not significantly reduce GGT levels. Conclusion : The study demonstrated that Moringa oleifera leaf extract and its combination with sitagliptin exhibited antidiabetic activity by decreasing blood glucose and HbA1c levels, antihyperlipidemic effects by stabilizing the lipid profile, and hepatoprotective effects by normalizing protein and liver enzyme levels. Furthermore, integrative therapy potentiates these effects at a comparatively lower dose.