Ormosanine confers protection on neuronal function via regulation of inflammatory cytokine levels and oxidative stress

Abstract


 
 
 
 Purpose: To investigate the neuroprotective effect of ormosanine on rat model of Alzheimer’s disease (AD), and the mechanism(s) of action involved.
 Methods: Rats were randomly assigned to 4 groups (10 rats/group): control group, AD group, 25 mg ormosanine/kg group, and 50 mg ormosanine/kg group. Alzheimer’s disease (AD) was induced in the rats via intracerebroventricular (ICV) injection of amyloid-β (Aβ)25-35 at a concentration of 1 mg/mL. Cognitive function was determined by Morris water maze test (MWMT), while lipid profile, oxidative stress parameters and cytokine level were assayed using their respective assay kits. The levels of monoamines were determined in brain tissues using high-performance liquid chromatography (HPLC), while terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay was used to determine apoptosis in neuronal cells.
 Results: Cognitive function was significantly improved (p < 0.05) in ormosanine treated group than AD group of rats. Ormosanine significantly and dose-dependently reduced lipid and cytokines levels as well as activities of AST and ALT, but it significantly increased the level of HDL-C in a dose-dependent fashion (p < 0.05). Moreover, ormosanine significantly and dose-dependently increased SOD activity, but reduced MDA level and neuronal cell apoptosis in brain tissues of AD rats (p < 0.05). Treatment of AD rats with ormosanine led to significant and dose-dependent increase in the levels of monoamines and BDNF in rat brain tissues (p < 0.05).
 Conclusion: These results show that ormosanine confers protection on neuronal function via regulation of inflammatory cytokine levels and oxidative stress, and therefore, could potentially be developed for the management of Alzheimer’s disease.