Neuroprotective effects of geniposide in the MPTP mouse model of Parkinson's disease

被引:81
作者
Chen, YiMei [1 ]
Zhang, Yanfang [1 ]
Li, Lin [1 ]
Hoelscher, Christian [2 ,3 ]
机构
[1] Shanxi Med Univ, Key Lab Cellular Physiol, Taiyuan, Shanxi, Peoples R China
[2] Univ Lancaster, Fac Hlth & Med, Biomed & Life Sci, Lancaster LA1 4YQ, England
[3] Shanxi Med Univ, Hosp 2, Taiyuan, Shanxi Province, Peoples R China
关键词
Neurodegeneration; Growth factor; Oxidative stress; Apoptosis; Dopamine; DOPAMINERGIC-NEURONS; MOTOR IMPAIRMENT; MEMORY DEFICITS; GENE-THERAPY; PC12; CELLS; RAT; EXPRESSION; MICE; APOPTOSIS; PATHWAY;
D O I
10.1016/j.ejphar.2015.09.029
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Parkinson's disease (PD) is a chronic neurodegenerative disease, and there is no cure for it at present. We tested the drug Geniposide, an active component of Gardenia jasminoides Ellis which is used in traditional Chinese medicine. Geniposide has shown neuroprotective and growth-factor like effects in several in vivo and in vitro studies. In the present study, Geniposide had been tested in an acute PD mouse model induced by four 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) intraperitoneal injections. Geniposide treatment (100 mg/kg ip.) for 8 days after MPTP treatment (30 mg/kg ip.) improved the locomotor and exploratory activity of mice (open field), and improved bradykinesia and movement balance of mice (rotarod, swim test). Geniposide treatment also restored tyrosine hydroxylase (TH) positive dopaminergic neuron numbers in the substantia nigra pars compacta. Drug treatment also increased levels of growth factor signaling molecule Bax and reduced the apoptosis signaling molecule Bcl-2. Caspase 3 activation was also reduced in the substantia nigra. We conclude that Geniposide exerted its neuroprotective effect by enhancing growth factor signaling and the reduction of apoptosis. Geniposide is an ingredient in Chinese traditional medicine with few known side effects and shows potential as a drug treatment for Parkinson's disease. (C) 2015 Elsevier B.V. All rights reserved.
引用
收藏
页码:21 / 27
页数:7
相关论文
共 46 条
[1]   Motor and Cognitive Advantages Persist 12 Months After Exenatide Exposure in Parkinson's Disease [J].
Aviles-Olmos, Iciar ;
Dickson, John ;
Kefalopoulou, Zinovia ;
Djamshidian, Atbin ;
Kahan, Joshua ;
Ell, Peter ;
Whitton, Peter ;
Wyse, Richard ;
Isaacs, Tom ;
Lees, Andrew ;
Limousin, Patricia ;
Foltynie, Thomas .
JOURNAL OF PARKINSONS DISEASE, 2014, 4 (03) :337-344
[2]   Exenatide and the treatment of patients with Parkinson's disease [J].
Aviles-Olmos, Iciar ;
Dickson, John ;
Kefalopoulou, Zinovia ;
Djamshidian, Atbin ;
Ell, Peter ;
Soderlund, Therese ;
Whitton, Peter ;
Wyse, Richard ;
Isaacs, Tom ;
Lees, Andrew ;
Limousin, Patricia ;
Foltynie, Thomas .
JOURNAL OF CLINICAL INVESTIGATION, 2013, 123 (06) :2730-2736
[3]   Effects of Gardeniae Fructus Extract and Geniposide on Promoting Ligament Cell Proliferation and Collagen Synthesis [J].
Chen, Quan Cheng ;
Zhang, Wei Yun ;
Kim, HongJin ;
Lee, Ik Soo ;
Ding, Yan ;
Youn, Ui Joung ;
Lee, Sang Myung ;
Na, MinKyun ;
Min, Byung-Sun ;
Bae, KiHwan .
PHYTOTHERAPY RESEARCH, 2010, 24 :S1-S5
[4]   Geniposide Ameliorates Learning Memory Deficits, Reduces Tau Phosphorylation and Decreases Apoptosis via GSK3β Pathway in Streptozotocin-Induced Alzheimer Rat Model [J].
Gao, Chong ;
Liu, Yueze ;
Jiang, Yuanhong ;
Ding, Jianming ;
Li, Lin .
BRAIN PATHOLOGY, 2014, 24 (03) :261-269
[5]   MPTP MECHANISMS OF NEUROTOXICITY AND THEIR IMPLICATIONS FOR PARKINSONS-DISEASE [J].
GERLACH, M ;
RIEDERER, P ;
PRZUNTEK, H ;
YOUDIM, MBH .
EUROPEAN JOURNAL OF PHARMACOLOGY-MOLECULAR PHARMACOLOGY SECTION, 1991, 208 (04) :273-286
[6]   Treatment of advanced Parkinson's disease [J].
Giugni, Juan C. ;
Okun, Michael S. .
CURRENT OPINION IN NEUROLOGY, 2014, 27 (04) :450-460
[7]   Swim-test as a function of motor impairment in MPTP model of Parkinson's disease: A comparative study in two mouse strains [J].
Haobam, R ;
Sindhu, KM ;
Chandra, G ;
Mohanakumar, KP .
BEHAVIOURAL BRAIN RESEARCH, 2005, 163 (02) :159-167
[8]   Insulin, incretins and other growth factors as potential novel treatments for Alzheimer's and Parkinson's diseases [J].
Hoelscher, Christian .
BIOCHEMICAL SOCIETY TRANSACTIONS, 2014, 42 :593-599
[9]  
Holscher C, 1996, BEHAV BRAIN RES, V81, P69
[10]   Mangiferin attenuates MPTP induced dopaminergic neurodegeneration and improves motor impairment, redox balance and Bcl-2/Bax expression in experimental Parkinson's disease mice [J].
Kavitha, Mani ;
Nataraj, Jagatheesan ;
Essa, Musthafa Mohammed ;
Memon, Mushtaq A. ;
Manivasagam, Thamilarasan .
CHEMICO-BIOLOGICAL INTERACTIONS, 2013, 206 (02) :239-247