Luteolin/ZnO nanoparticles attenuate neuroinflammation associated with diabetes via regulating MicroRNA-124 by targeting C/EBPA

Abstract

Objective: The most prevalent brain-specific microRNA, MicroRNA-124, exhibits anti-inflammatory properties. Luteolin nano-formulation with Zn oxide in the form of L/ZnO NPs may boost anti-diabetic properties; however, its beneficial effect on miRNAs is yet unknown in diabetes. The effectiveness of L/ZnONPs supplements in preventing diabetic neurodegeneration by modulating inflammatory responses in a diabetic model was investigated. Methods: A diabetic rat model was induced by a high-fat diet and streptozotocin (30 mg/kg I.P.). Plasma glucose, insulin, and HOMR-IR levels, as well as cytokines, lipid peroxidation, GSH/GSSG, and glucose transporter 1, were determined along with the tight junction proteins occludin (OCLN) and zona occludens 1 (ZO-1). Moreover, the expressions of brain CCAAT/enhancer-binding protein (C/EBPA mRNA), miR-124, glial fibrillary acidic protein (GFAP), and NF-kBp65 were measured alongside the histological investigation. Results: The results revealed that L/ZnO NPs were able to diminish lipid peroxidation, increase the activity of antioxidant enzymes, and reduce inflammation under oxidative stress. Consequently, it was able to reduce hyperglycemia, elevate insulin levels, and improve insulin resistance. Besides, L/ZnO NPs upregulate miR-124, reduce C/EBPA mRNA, increase BCl-2, and inhibit apoptosis. The results indicate that diabetes raises BBB permeability via tight junction protein decline, which is restored following L/ZnO NPs treatment. Luteolin/ZnO NPs regulate miR-124 and microglia polarization by targeting C/EBPA and are expected to alleviate inflammatory injury via modulation of the redox-sensitive signal transduction pathways. Luteolin/ZnO NPs have a novel target for the protection of the BBB and the prevention of neurological complications in diabetes.