Bioengineered AgNPs from Lepidagathis Pungens Extract Enhance GLUT4 and PPARγ

Introduction: Diabetes mellitus is a chronic metabolic disorder associated with hyperglycemia, oxidative stress, and long-term complications. Conventional therapies often lose efficacy and cause adverse effects. Green-synthesized silver nanoparticles (AgNPs) of-fer a biocompatible and sustainable alternative. This study evaluated the antidiabetic efficacy of Lepidagathis Pungens-mediated AgNPs (LP-AgNPs). Method: LP-AgNPs were synthesized using ethanol extract of Lepidagathis pungens and characterized by UV-Vis, SEM, TEM, FTIR, XRD, and zeta potential analysis. In vitro as-says in 3T3-L1 adipocytes assessed cytotoxicity and GLUT4/PPARγ expression. In vivo efficacy was evaluated in streptozotocin–nicotinamide-induced diabetic Wistar rats treated with LP-AgNPs (50 and 100 mg/kg) for 21 days, with Metformin (150 mg/kg) as reference. Biochemical parameters, oxidative stress markers, and histopathology were analyzed. Results: LP-AgNPs were spherical (20–30 nm) and stable, showing reproducible drug re-lease. In vitro, LP-AgNPs significantly upregulated GLUT4 and PPARγ expression, levels comparable to those of Metformin. In vivo, LP-AgNPs reduced fasting glucose (up to 60%, p <0.001), lowered malondialdehyde (45%), and enhanced SOD and CAT activities. Insulin levels and HbA1c improved markedly, while liver and renal markers indicated protective effects. Histopathology confirmed preservation of pancreatic, hepatic, and renal tissues. Discussion: The therapeutic potential of LP-AgNPs is attributed to nanoparticle-mediated delivery and phytochemical synergy, enhancing insulin sensitivity and antioxidative de-fense. Compared with standard therapy, LP-AgNPs addressed both hyperglycemia and oxi-dative stress, providing broader benefits. Conclusion: LP-AgNPs exhibit potent antidiabetic and antioxidative effects, highlighting their promise as a natural, eco-friendly nanotherapeutic for diabetes. Long-term and clinical studies are warranted.