Inhibition of gene expression and production of iNOS and TNF-α in experimental model of neurodegenerative disorders stimulated microglia by Soy nano-isoflavone/stem cell-exosomes

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 ?? (TNF-??), 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-??, and i-NOS pathway-encoding genes. Furthermore, BMSC-EXs and nanoisoflavone 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.

Automated summary

This study evaluated the therapeutic potential of soybean nano-isoflavone extract and bone marrow mesenchymal stem cells derived extracellular exosomes in experimentally induced neurodegenerative diseases in rats. The results showed that both treatments repaired damaged cerebral tissue and recovered its function greatly, with favorable therapeutic utility against D-galactose-induced neurodegenerative disease.