Pharmacological Investigation of Oryza sativa Antioxidants in Neurodegeneration

Abstract

Oryza sativa serves as a staple food worldwide and it is enriched with essential phytophenolic chemical constituents which possess plenty of disease modulating features. γ-Oryzanol (OZ) and Ellagic acid (EA) are chemically phenolic phytoconstituents having prominent anti-oxidative effects and have potentials to modulate molecular biochemistry in beneficial way. Hence, current investigation was aimed to evaluate neuroprotective and cognitive enhancement effects of Oryza sativa phytophenolic constituents in STZ induced SAD/ LOAD and Aβ (1-42) induced EAOD in animal models. Both these animal models mimic the pathological relevance of neurodegenerative ailments as in humans. In silico experiments suggested target specificity of FA, OZ and EA for AchE and Aβ (1-42). Our findings suggested the safety and cytoprotective profile of Oryza sativa phytoconstituents in presence of neurotoxins in the SH-SY5Y human neuroblastoma cell line. Furthermore, antioxidative effect by DPPH assay, anti-AchE effect against AchE enzyme from Electrophorus electricus and Aβ (1-42) antiaggregatory effects fulfilled prime requirements of Oryza sativa phytochemicals to get explored further for neurodegenerative ailments. The in vivo experiments suggested therapeutic effects of FA, OZ and EA in STZ induced LOAD and Aβ (1-42) induced EOAD with reference to their biochemical as well as behavioural modulatory features. 30 days treatment of OZ (100 mg/kg, p.o.) and EA (50 mg/kg, p.o.) in STZ (3 mg/kg i.c.v.) induced SAD showed correction of biochemical abnormalities by improvement in oxidative stress profile, retardation of pro-inflammatory markers i.e. GFAP and CRP, AchE level, and Aβ plaque level. Treatment of EA i.e. EA70 and EA140 (single dose of 70 μM and140 μM respectively, i.c.v.) in Aβ (1-42) (10μL, 1μg/μL, i.c.v.) treated animals signified Aβ (1-42) anti-aggregatory effect, Ca+ +/Calpain/GSK-3β/CDK5 modulatory, anti-tauopathic effects. Furthermore the study signified anti-inflammatory effects through prevention of astroglial activation, modification of FAIM-L expression and subsequent protection from TNF-α induced death signals. The neuromodulatory effects of EA was due to regulation of CREB level, dynamin-1 expression and synaptophysin level which supported properties of EA to modify LTP and synaptic plasticity. Oryza sativa phytoconstituents revealed beneficial cytological and behavioural modulation in context of improvement in long term, short term spatial memory as well as associative learning behaviour in animals which indicated cognitive enhancement effects of OZ and EA.