Mulberry fruit protects dopaminergic neurons in toxin-induced Parkinson's disease models.
Parkinson's disease (PD), one of the most common neurodegenerative disorders, is characterised by the loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc) to the striatum (ST), and involves oxidative stress. Mulberry fruit from Morus alba L. (Moraceae) is commonly eaten, and has long been used in traditional oriental medicine. It contains well-known antioxidant agents such as anthocyanins. The present study examined the protective effects of 70 % ethanol extract of mulberry fruit (ME) against neurotoxicity in in vitro and in vivo PD models. In SH-SY5Y cells stressed with 6-hydroxydopamine (6-OHDA), ME significantly protected the cells from neurotoxicity in a dose-dependent manner. Other assays demonstrated that the protective effect of ME was mediated by its antioxidant and anti-apoptotic effects, regulating reactive oxygen species and NO generation, Bcl-2 and Bax proteins, mitochondrial membrane depolarisation and caspase-3 activation. In mesencephalic primary cells stressed with 6-OHDA or 1-methyl-4-phenylpyridinium (MPP+), pre-treatment with ME also protected dopamine neurons, showing a wide range of effective concentrations in MPP+-induced toxicity. In the sub-acute mouse PD model induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), ME showed a preventative effect against PD-like symptoms (bradykinesia) in the behavioural test and prevented MPTP-induced dopaminergic neuronal damage in an immunocytochemical analysis of the SNpc and ST. These results indicate that ME has neuroprotective effects in in vitro and in vivo PD models, and that it may be useful in preventing or treating PD.
Kim
Hyo Geun
HG
Department of Oriental Pharmaceutical Science and Kyung Hee East-West Pharmaceutical Research Institute, College of Pharmacy, Kyung Hee University, Dongdaemun-gu, Seoul 130-701, South Korea.
Ju
Mi Sun
MS
Shim
Jin Sup
JS
Kim
Min Cheol
MC
Lee
Sang-Hun
SH
Huh
Youngbuhm
Y
Kim
Sun Yeou
SY
Oh
Myung Sook
MS
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D002460:Cell Line; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005638:Fruit; D006801:Humans; D020267:MPTP Poisoning / Q000188:drug therapy* / Q000378:metabolism; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051379:Mice; D031625:Morus; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use; D009498:Neurotoxins / Q000494:pharmacology; D009569:Nitric Oxide / Q000096:biosynthesis; D016627:Oxidopamine / Q000494:pharmacology; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism
D000975:Antioxidants; D018696:Neuroprotective Agents; D009498:Neurotoxins; D010936:Plant Extracts; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; D009569:Nitric Oxide; D016627:Oxidopamine; D004298:Dopamine