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Metab Brain Dis ; 38(2): 557-571, 2023 Feb.
Article in English | MEDLINE | ID: mdl-36401682

ABSTRACT

Parkinson's disease (PD) is a neurodegenerative disorder characterized by both motor and non-motor features. The current treatment regimen for PD are dopamine enhancers which have been reported to worsen the disease prognosis after long term treatment, thus, the need for better treatment options. This study sought to investigate the protective action of Double Stem Cell® (DSC), a blend of stem cells extracts from Swiss apples (Malus Domestica) and Burgundy grapes (Vitis vinifera) on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinsonism in mice and genetic model of PD in Drosophila melanogaster. Male albino mice were pretreated with MPTP (4 × 20 mg/kg, i.p., two hourly in 8 h), twelve hours before administration of DSC (8, 40, or 200 mg/kg, p.o.). Thereafter, behavioural, biochemical and immunohistochemical assays were carried out. The impact of vehicle or DSC supplementation on α-synuclein aggregation was evaluated in Drosophila melanogaster using the UAS-Gal4 system, female DDC-Gal4 flies were crossed with male UAS-α-synuclein, the progenies were examined for fecundity, locomotion, memory, and lifespan. MPTP-induced motor deficits in open field test (OFT), working memory impairment (Y-maze test (YMT)) and muscle incoordination (rotarod test) were ameliorated by DSC (8, 40 or 200 mg/kg) through dose-dependent and significant improvements in motor, cognitive and motor coordination. Moreso, MPTP exposure caused significant increase in lipid peroxidation and decrease in antioxidant enzymes activities (glutathione, catalase and superoxide dismutase) in the midbrain which were attenuated by DSC. MPTP-induced expression of microglia (iba-1), astrocytes (glia fibrillary acidic protein; GFAP) as well as degeneration of dopamine neurons (tyrosine hydroxylase positive neurons) in the substantia nigra (SN) were reversed by DSC. Supplementation of flies feed with graded concentration of DSC (0.8, 4 or 20 mg/ml) did not affect fecundity but improved climbing activity and lifespan. Findings from this study showed that Double Stem Cell improved motor and cognitive functions in both mice and Drosophila through attenuation of neurotoxin-induced oxidative stress and neuroinflammation.


Subject(s)
Neuroprotective Agents , Parkinson Disease , Plant Extracts , Animals , Mice , 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine/metabolism , 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine/pharmacology , alpha-Synuclein/metabolism , Antioxidants/pharmacology , Disease Models, Animal , Dopaminergic Neurons/metabolism , Drosophila melanogaster , Mice, Inbred C57BL , Models, Genetic , Neuroinflammatory Diseases , Neuroprotective Agents/pharmacology , Neuroprotective Agents/therapeutic use , Oxidative Stress , Parkinson Disease/metabolism , Substantia Nigra/metabolism , Plant Extracts/pharmacology
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