Abstract
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•Degeneration of the brain tissue is related to cell apoptosis, axonal failure to regenerate, and demyelination, that lead to abnormal structure and function of neurons and the occurrence of neurodegenerative disorders is in increasable, due to increased lifespan.•D-galactose is present usually in the human body as one of the reducing sugars and is used frequently to induce brain aging in animal models as chronic systemic exposure of D-galactose causes the acceleration of gradual deterioration of functional characteristics of organs.•Isoflavones are phytoestrogens of plant origin, mostly found in the members of the Fabaceae family, that exert beneficial effects in various degenerative disorders. Having high similarity to 17-βestradiol, isoflavones can bind estrogen receptors, scavenge reactive oxygen species, activate various cellular signal transduction pathways, and modulate growth and transcription factors, activities of enzymes, cytokines, and genes regulating cell proliferation and apoptosis. Isoflavones prevent oxidative stress induced by Aβ-peptide in neuronal cells.•The use of bone MSCs-derived extracellular exosomes (BMSCs-EXs) exhibits potential therapeutic effects like MSCs through mediate the paracrine activities of MSCs.•BMSCs-EXs have emerged as a promising therapeutic approach for the treatment of neurodegenerative disease as improvement in oxidant/antioxidant balance and through their paracrine activity.
The present study evaluated the therapeutic potential of soybean nano-isoflavone extract versus bone marrow mesenchymal stem cells derived extracellular exosomes (BMSCs-EXs) in experimentally induced neurodegenerative diseases in rats (ND). In this study, 36 albino male rats were divided into four groups: Group I (control rats); Group II (induced neurodegenerative disease in rats by intraperitoneal injection of d-galactose (120 mg/kg/day for 2 months); Group III (ND-induced rats treated with nano-isoflavone in doses of 10 mg/kg by oral gavage for 3 months); and Group IV (ND-induced rats treated with a single dose injection of BMSCs-EXs. The effect of BMSCs-EXs was evaluated by cerebral oxidant/antioxidant biomarkers, and mRNA gene expression quantitation for cerebral tumor necrosis factor α (TNF-α), inducible nitric oxide synthase (i-NOS) and GAPDH pathway-encoding genes by real time reverse transcription polymerase chain reaction (RT-PCR) techniques. Then, histopathological examination of the cerebral cortical tissues. Our results showed that BMSC-EXs were successfully isolated and characterized. d-galactose produced a significant rise in the number of damaged neurons, decreased cerebral superoxide dismutase and catalase activities, increased cerebral malondialdehyde levels, downregulated the cerebral TNF-α, and i-NOS pathway-encoding genes. Furthermore, BMSC-EXs and nano-isoflavone treatments repaired damaged cerebral tissue and recovered its function greatly following induction of neurodegenerative disease. Treatment with either MSCs-EXs or nano-isoflavones led to significant improvement in the histological findings, reversed the degenerative effect of d-galactose, and had a favorable therapeutic utility against d- galactose-induced neurodegenerative disease.