Comparative antidiabetic effects of Cymbopogon citratus leaf extract, derived silver nanoparticles, and their combination in alloxan-induced diabetic mice.

Abstract

Plant-mediated nanoparticles are being investigated for metabolic disorders, but therapeutic gains from full-dose co-administration should be distinguished from true pharmacological synergy. This study compared the antidiabetic effects of Cymbopogon citratus leaf ethanolic extract (LEE), biosynthesized silver nanoparticles (AgNPs), and their combination in alloxan-induced diabetic mice. AgNPs were synthesized using LEE as a reducing and capping agent and characterized by UV-Vis spectroscopy, dynamic light scattering, zeta potential analysis, transmission electron microscopy, Fourier-transform infrared spectroscopy, and X-ray diffraction. The AgNPs showed a surface plasmon resonance peak at 432 nm, mean hydrodynamic diameter of 38.2 ± 4.6 nm, zeta potential of -28.4 ± 3.1 mV, and predominantly spherical morphology. Diabetic mice received metformin, LEE, AgNPs, or LEE + AgNPs for 28 days, followed by evaluation of glycaemic, oxidative, lipid, hepatorenal, haematological, pancreatic histopathological, and integrated biomarker recovery responses. The combination group recorded fasting blood glucose of 128.0 ± 3.0 mg/dL and HbA1c of 6.5 ± 0.1%, compared with 141.0 ± 5.7 mg/dL and 7.3 ± 0.1%, respectively, in the AgNP group. Although combined administration produced the highest integrated biomarker recovery index (80.61 ± 0.61%), additional improvements over AgNP monotherapy were limited or nonsignificant across several endpoints. Pancreatic histopathology also showed improved islet area, cellular density, and lesion scores following treatment. Co-administration produced endpoint-specific additional benefits but did not demonstrate pharmacological synergy. Further route-matched dose-response studies, mechanistic validation, nanoparticle biodistribution, and long-term biosafety assessment are required.