In vivo multi-omics evaluation of ellagic Acid–Gold nanoparticles from Syzygium cumini for glycemic improvement and β-cell preservation in type 2 diabetic mice

Abstract

Diabetes mellitus remains a major global health challenge, affecting over 537 million adults worldwide and this number is expected to rise 783 million by 2045, underscoring the need for improved therapeutic strategies. In this study, we synthesized and evaluated ellagic-acid-loaded gold nanoparticles (EA-AuNPs) prepared from Syzygium cumini seed extract as a potential antidiabetic intervention. EA-AuNPs exhibited a spherical morphology with an average size of 68.4 ± 5.2 nm, zeta potential of −24.6 mV, and encapsulation efficiency of 81.3 ± 2.7 %, indicating stability and optimal drug-loading capacity. In vivo testing in streptozotocin-induced diabetic mice (n = 40) revealed that EA-AuNPs (25 mg/kg, orally, for 28 days) reduced fasting blood glucose by 68.3 % (p < 0.001) and HbA1c by 43.5 % (p < 0.01), while enhancing serum insulin by 2.8-fold. Histological assessment showed restoration of islet morphology with an increase in β-cell area, consistent with protective and recovery-associated effects. Multi-omics analyses supported modulation of metabolic and inflammatory pathways, including PI3K/AKT, AMPK, and NF-κB, consistent with improved glucose homeostasis and reduced oxidative stress (MDA ↓52.4 %, SOD ↑2.1-fold). Collectively, these findings suggest that EA-AuNPs may offer a promising nanophytochemical approach for managing Type 2 diabetes, warranting further mechanistic and translational investigation.