Ishola I O, Oloyo A K, Olubodun-Obadun T G, Godswill O D, Omilabu S A, Adeyemi O O
Department of Pharmacology, Therapeutics and Toxicology, Faculty of Basic Medical Sciences, College of Medicine, University of Lagos, Lagos, Lagos State, Nigeria.
Department of Physiology, Faculty of Basic Medical Sciences, College of Medicine, University of Lagos, Lagos, Lagos State, Nigeria.
Metab Brain Dis. 2023 Feb;38(2):557-571. doi: 10.1007/s11011-022-01120-3. Epub 2022 Nov 19.
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.
帕金森病(PD)是一种以运动和非运动特征为特点的神经退行性疾病。目前针对PD的治疗方案是多巴胺增强剂,但据报道长期治疗后会使疾病预后恶化,因此需要更好的治疗选择。本研究旨在探究双干细胞(DSC)(一种来自瑞士苹果(苹果属)和勃艮第葡萄(葡萄属)的干细胞提取物混合物)对1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP)诱导的小鼠帕金森症以及黑腹果蝇PD基因模型的保护作用。雄性白化小鼠在腹腔注射MPTP(4×20mg/kg,每两小时一次,共8小时)前12小时,经口给予DSC(8、40或200mg/kg)进行预处理。此后,进行行为学、生物化学和免疫组织化学检测。使用UAS-Gal4系统在黑腹果蝇中评估载体或补充DSC对α-突触核蛋白聚集的影响,雌性DDC-Gal4果蝇与雄性UAS-α-突触核蛋白果蝇杂交,检测后代的繁殖力、运动能力、记忆力和寿命。DSC(8、40或200mg/kg)通过剂量依赖性且显著改善运动、认知和运动协调能力,减轻了MPTP在旷场试验(OFT)中诱导的运动缺陷、工作记忆损害(Y迷宫试验(YMT))和肌肉不协调(转棒试验)。此外,MPTP暴露导致中脑脂质过氧化显著增加,抗氧化酶活性(谷胱甘肽、过氧化氢酶和超氧化物歧化酶)降低,而DSC可使其减弱。DSC逆转了MPTP诱导的小胶质细胞(iba-1)、星形胶质细胞(胶质纤维酸性蛋白;GFAP)的表达以及黑质(SN)中多巴胺能神经元(酪氨酸羟化酶阳性神经元)的变性。用不同浓度(0.8、4或20mg/ml)的DSC补充果蝇饲料不影响繁殖力,但改善了攀爬活动和寿命。本研究结果表明,双干细胞通过减轻神经毒素诱导的氧化应激和神经炎症,改善了小鼠和果蝇的运动和认知功能。