title: Grape extract protects mitochondria from oxidative damage and improves locomotor dysfunction and extends lifespan in a Drosophila Parkinson's disease model.
abstract: A botanical extract (Regrapex-R) prepared from whole grape (Vitis vinifera) and Polygonum cuspidatum, which contains polyphenols, including flavans, anthocyanins, emodin, and resveratrol, exhibited dose-dependent scavenging effects on reactive oxygen species (ROS). The extract inhibited increases of ROS and protein carbonyl in isolated rat liver mitochondria following exposure to 2,2'-azobis (2-amidino propane) dihydrocholoride (AAPH), a potent lipid oxidant generator. The antioxidant effects of this extract were further demonstrated by protecting enzyme activities of the mitochondrial respiratory electron transport chain (complexes I and II) and pyruvate dehydrogenase in isolated liver mitochondria with AAPH insult. In human neuroblastoma cells (SKN-MC), pretreatment of extract protected cells against AAPH induced oxidation in maintaining cell viability and inhibiting excessive ROS generation. Extract was fed to transgenic Drosophila expressing human alpha-synuclein. This model for Parkinson disease recapitulates essential features of the disorder, including loss of dopaminergic neurons in the substantia nigra and a locomotor dysfunction that is displayed by a progressive loss of climbing ability measured using a geotaxis assay. Male transgenic flies fed the extract (0.16-0.64 mg/100 g of culture medium) showed a significant improvement in climbing ability compared to controls. Female transgenic flies showed a significant extension in average lifespan. These results suggest that Regrapex-R is a potent free radical scavenger, a mitochondrial protector, and a candidate for further studies to assess its ability to protect against neurodegenerative disease and potentially extend lifespan.
authors.affiliation: Institute of Mitochondrial Biology and Medicine, Department of Biology and Engineering, The Key Laboratory of Biomedical Information Engineering of Ministry of Education, Xi'an Jiaotong University School of Life Science and Technology, Xi'an, China.
authors.forename: Jiangang
authors.initials: J
authors.lastname: Long
authors.forename: Hongxiang
authors.initials: H
authors.lastname: Gao
authors.forename: Lijuan
authors.initials: L
authors.lastname: Sun
authors.forename: Jiankang
authors.initials: J
authors.lastname: Liu
authors.forename: Xi
authors.initials: X
authors.lastname: Zhao-Wilson
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D000975:Antioxidants / Q000378:metabolism; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D004331:Drosophila melanogaster / Q000378:metabolism*; D006801:Humans; D008297:Male; D008928:Mitochondria / Q000378:metabolism*; D009068:Movement; D018384:Oxidative Stress / Q000187:drug effects*; D010300:Parkinson Disease / Q000628:therapy*; D010936:Plant Extracts / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species; D027843:Vitis / Q000378:metabolism*; D051844:alpha-Synuclein / Q000737:chemistry
chemical_list: D000975:Antioxidants; D010936:Plant Extracts; D017382:Reactive Oxygen Species; D051844:alpha-Synuclein