Neuroprotective effects of rutin, sodium selenite, and rutin-conjugated selenium nanoparticles in a social isolation model

Abstract

Background Social isolation (SI) is a long-standing experimental paradigm that models schizophrenia-like behavioural and neurobiological changes caused by the action of oxidative stress, neuroinflammation, apoptosis, and neurotransmitter imbalance. The scope of this paper was to comparatively assess the effectiveness of rutin, sodium selenite (Na 2 SeO 3 ), and rutin-conjugated selenium nanoparticles (RUT-SeNPs) to determine their neuroprotective activity using a rat model of neurobehavioral impairment following SI. Methods In silico analysis of Rutin activity including in silico ADMET and toxicity, and molecular docking. Forty-two healthy male albino rats were allocated equally in to six groups; Control group, Social isolation group (SI), SI treated with Olanzapine (SI&OLA), SI treated with Rutin group (SI&RUT), SI treated with the sodium selenite group (SI&Na 2 SeO 3 ), and SI treated with Se nanoparticles biosynthesized using the Rutin group (SI&RUT-SeNPs). All groups undergone biochemical analysis including behavioral tests, assessment of neural function, oxidative stress, inflammation, and apoptosis, histopathological analysis, immunohistochemistry, and gene expression. Results SI induction produced significant behavioral, biochemical, neurochemical, and structural impairments compared with controls ( P < 0.05). SI rats showed marked reductions in locomotion, sucrose preference, social interaction, antioxidant capacity (Nrf2, SOD, CAT, GSH), neurotransmitters (serotonin, dopamine, GABA, glycine), and BDNF, alongside significant increases in oxidative stress markers (8-OHdG, MDA, NO), inflammatory cytokines (TNF-α, IL-1β, NF-κB), apoptotic mediators (Bax and Caspase-3), GFAP, and histological degeneration ( P < 0.05). Across all assessments, RUT-SeNPs produced the strongest and statistically significant recovery, yielding values comparable to control and significantly superior to SI, SI&OLA, and SI&RUT groups ( P < 0.05). RUT-SeNPs normalized behavioral outcomes, antioxidant status, cytokine levels, apoptotic markers, neurotransmitters, BDNF/GFAP balance, and cortical histoarchitecture. Conclusion Rutin and sodium selenite provided significantly protective effects across behavioral, biochemical, and neurochemical parameters. Among all treatments, RUT-SeNPs produced markedly attenuated, restoring nearly all measured markers including redox balance, cytokines, apoptosis regulators, neurotransmitters, BDNF/GFAP levels, and cortical histology to values comparable to controls.