D-Pinitol improves cognitive dysfunction and neuronal damage induced by isoproterenol via modulation of NF-κB/BDNF/GFAP signaling in Swiss albino mice

Objective(s): Neurological disorders are the world’s most distressing problem. The adverse effects of current medications continue to compel scientists to seek safer, more effective, and economically affordable alternatives. In this vein, we explored the effect of D-Pinitol on isoproterenol-induced neurotoxicity in mice.Materials and Methods: Forty-two mice were randomly distributed into ۷ groups each having ۶ animals. Group I; received saline. Group II; received isoproterenol (ISO) ۱۵ mg/kg/day, s.c. for ۲۰ days. Group III, IV; received ۵۰ and ۱۰۰ mg/kg/day/oral of D-Pinitol, respectively along with ISO for ۲۰ days. Group V; received D-Pinitol ۱۰۰ mg/kg/day/oral for ۲۰ days. Group VI; received propranolol ۲۰ mg/kg/day/oral and ISO for ۲۰ days. Group VII; received propranolol ۲۰ mg/kg/day/oral for ۲۰ days. On the ۲۱st day after behavioral tests, blood was collected and mice were sacrificed for various biochemical, histopathological, and immunohistochemical analyses.Results: Chronic administration of isoproterenol caused neurotoxicity, cognitive dysfunction, and histopathological changes in the brain as evidenced by increase in GFAP, oxidative stress (via SOD, CAT, TBARS, and GSH), neuroinflammation  (NF-kB, TNF-α, IL-۶, and IL-۱۰), and decrease in AchE and BDNF. Co-administration of D-Pinitol (۱۰۰ mg/kg) significantly prevented these pathological alterations. The cognitive improvement was also observed through the forced swim test, elevated plus maze test, and rotarod test.Conclusion: Our findings on D-Pinitol thus clearly established its neuroprotective role in ISO-induced neurodegeneration in Swiss albino mice.

کلیدواژه ها:

D-Pinitol ، Inflammation ، Isoproterenol ، Neuroprotection ، Neurotoxicity ، Oxidative stress