Green-synthesized Salvia officinalis-conjugated Selenium Nanoparticles Mitigate Diabetic Complications via Multi-target Molecular and Histopathological Restoration in STZ-induced Mice

Abstract

Diabetes mellitus is a chronic metabolic disease characterized by hyperglycemia and oxidative stress, which can lead to serious complications. In recent years, with the development of nanomedicine, selenium nanoparticles (SeNPs) have emerged as promising therapeutic agents due to their antioxidant and insulin-mimetic properties. This experiment aimed to evaluate the therapeutic efficacy of selenium nanoparticles prepared from Salvia officinalis leaves extract (SOLE–SeNPs) on metabolic, oxidative, inflammatory, and histopathological complications in STZ-induced diabetic mice SOLE-SeNPs were synthesized by an aqueous leaf extract as both a natural reducing and capping agent. TEM, DLS, zeta potential, UV–Vis spectroscopy, and FTIR techniques were used for the characterization of nanomaterials with regard to morphology, particle size, surface charge, optical properties, and biomolecular interaction. Male mice were classified into five groups, and two doses of SOLE-SeNPs (21.4 and 53.5 mg/kg) or glibenclamide (600 µg/kg) were administered for 21 days after STZ treatment to induce diabetes. Glucose, insulin, lipid profile, oxidative stress markers (GSH, SOD, and MDA), cytokine levels (IL-6 and TGF-β1), gene expression analysis (Bcl-2, GK, and GLUT2), as well as hepatic histopathology were evaluated for therapeutic assessment. Nanoparticle characterisation verified the successful synthesis with spherical shape (diameter 75 nm), good dispersity (DLS peak 60 nm), and high colloidal stability (zeta potential: - 44.84 mV). SOLE-SeNPs, especially at high doses, significantly decreased plasma glucose and triglyceride levels, accompanied by increased insulin and HDL-C levels, along with total cholesterol recovery. Elevated GSH and SOD, along with decreased MDA, confirm the powerful antioxidant effect of SOLE-SeNPs. Pro-inflammatory cytokines were markedly reduced. At the molecular level, we observed upregulation of Bcl-2 and GK in the pancreas and modest modulation of GLUT2 in the liver. Histopathological evaluation indicated almost restored hepatic architecture with high-dose SOLE-SeNPs treatment, outperforming glibenclamide in most parameters The results of this study showed that the SeNPs synthesized by SOLE extract have notable antidiabetic and antioxidant activities, which implies a combination of selenium bioactivity and some other phytochemical compounds in S. officinalis. These findings confirm the mode of action previously reported for nanoparticle-mediated therapy through an exciting new, environmentally friendly synthesis method. Limitations: Brief treatment duration and no assessment of long-term toxicities SOLE-SeNPs possessed strong and dose-dependent efficacy in preventing diabetic complications through a comprehensive set of metabolic, antioxidant, anti-inflammatory, and gene-modulatory actions. The phytoconjugated character assures their synergistic bioactivity, making them a novel green nanoplatform for diabetes treatment. The long-term safety, biodistribution, and cellular pathways must be investigated in future studies to further confirm the clinical application.