Neuroprotective and anti-inflammatory effects of morin in a murine model of Parkinson's disease

被引:66
作者
Lee, Kyung Moon [1 ]
Lee, Yujeong [1 ]
Chun, Hye Jeong [1 ]
Kim, Ah Hyun [1 ]
Kim, Ju Yeon [1 ]
Lee, Joo Yeon [1 ]
Ishigami, Akihito [2 ]
Lee, Jaewon [1 ]
机构
[1] Pusan Natl Univ, Dept Pharm, Mol Inflammat Res Ctr Aging Intervent, Coll Pharm, Busan 609735, South Korea
[2] Tokyo Metropolitan Inst Gerontol, Mol Regulat Aging, Tokyo, Japan
基金
新加坡国家研究基金会;
关键词
morin; MPTP; oxidative stress; mitochondrial dysfunction; neuroinflammation; astrocyte; Parkinson's disease; NF-KAPPA-B; MPTP MOUSE MODEL; OXIDATIVE STRESS; MITOCHONDRIAL DYSFUNCTION; ASTROGLIAL ACTIVATION; BRAIN; ASTROCYTES; CELLS; INHIBITION; APOPTOSIS;
D O I
10.1002/jnr.23764
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Parkinson's disease (PD) is one of the most common neurodegenerative disorders and is characterized by loss of dopaminergic neurons in the substantia nigra (SN). Although the causes of PD are not understood, evidence suggests that oxidative stress, mitochondrial dysfunction, and inflammation are associated with its pathogenesis. Morin (3,5,7,2,4-pentahydroxyflavone) is a flavonol found in wine and many herbs and fruits. Previous studies have suggested that morin prevents oxidative damage and inflammation and ameliorates mitochondrial dysfunction. The present study describes the neuroprotective effects of morin in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model of PD, and we report the results of our investigation into its neuroprotective mechanism in primary neurons and astrocytes. In the mouse model, morin pretreatment ameliorated motor dysfunction, protected against dopaminergic neuronal losses in SN and striatum, and alleviated MPTP-induced astrocyte activation. In vitro studies revealed that morin protected primary cultured neurons against 1-methyl-4-phenylpyridine (MPP+)-mediated reactive oxygen species production and mitochondrial membrane potential (MMP) disruption. In addition, morin effectively reduced MPP+-induced astroglial activation and nuclear translocation of nuclear factor-B in primary cultured astrocytes. These results indicate that morin acts via multiple neuroprotective mechanisms in our mouse model and suggest that morin be viewed as a potential treatment and preventative for PD. (c) 2016 Wiley Periodicals, Inc.
引用
收藏
页码:865 / 878
页数:14
相关论文
共 69 条
[1]   Mitochondrial oxidative stress and dysfunction induced by isoniazid: study on isolated rat liver and brain mitochondria [J].
Ahadpour, Morteza ;
Eskandari, Mohammad Reza ;
Mashayekhi, Vida ;
Tehrani, Kamaleddin Haj Mohammad Ebrahim ;
Jafarian, Iman ;
Naserzadeh, Parvaneh ;
Hosseini, Mir-Jamal .
DRUG AND CHEMICAL TOXICOLOGY, 2016, 39 (02) :224-232
[2]   MORIN, A FLAVONOID, ON LIPID PEROXIDATION AND ANTIOXIDANT STATUS IN EXPERIMENTAL MYOCARDIAL ISCHEMIC RATS [J].
Al-Numair, Khalid S. ;
Chandramohan, Govindasamy ;
Alsaif, Mohammed A. ;
Veeramani, Chinnadurai ;
El Newehy, Ahmed S. .
AFRICAN JOURNAL OF TRADITIONAL COMPLEMENTARY AND ALTERNATIVE MEDICINES, 2014, 11 (03) :14-20
[3]   Probenecid potentiates MPTP/MPP+ toxicity by interference with cellular energy metabolism [J].
Alvarez-Fischer, Daniel ;
Noelker, Carmen ;
Gruenewald, Anne ;
Vulinovic, Franca ;
Guerreiro, Serge ;
Fuchs, Julia ;
Lu, Lixia ;
Lombes, Anne ;
Hirsch, Etienne C. ;
Oertel, Wolfgang H. ;
Michel, Patrick P. ;
Hartmann, Andreas .
JOURNAL OF NEUROCHEMISTRY, 2013, 127 (06) :782-792
[4]   Monoamine oxidase-B mediates ecstasy-induced neurotoxic effects to adolescent rat brain mitochondria [J].
Alves, Ema ;
Summavielle, Teresa ;
Alves, Cecilia Juliana ;
Gomes-da-Silva, Joana ;
Barata, Jose Custodio ;
Fernandes, Eduarda ;
Bastos, Maria de Lourdes ;
Tavares, Maria Amelia ;
Carvalho, Felix .
JOURNAL OF NEUROSCIENCE, 2007, 27 (38) :10203-10210
[5]   Targeted studies on the interaction of nicotine and morin molecules with amyloid β-protein [J].
Boopathi, Subramaniam ;
Kolandaivel, Ponmalai .
JOURNAL OF MOLECULAR MODELING, 2014, 20 (03)
[6]   SYSTEMIC 3-NITROPROPIONIC ACID - BEHAVIORAL DEFICITS AND STRIATAL DAMAGE IN ADULT-RATS [J].
BORLONGAN, CV ;
KOUTOUZIS, TK ;
RANDALL, TS ;
FREEMAN, TB ;
CAHILL, DW ;
SANBERG, PR .
BRAIN RESEARCH BULLETIN, 1995, 36 (06) :549-556
[7]   The parkinsonian neurotoxin MPP+ opens the mitochondrial permeability transition pore and releases cytochrome c in isolated mitochondria via an oxidative mechanism [J].
Cassarino, DS ;
Parks, JK ;
Parker, WD ;
Bennett, JP .
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE, 1999, 1453 (01) :49-62
[8]   Tetrahydrobiopterin causes mitochondrial dysfunction in dopaminergic cells: Implications for Parkinson's disease [J].
Choi, HJ ;
Lee, SY ;
Cho, Y ;
No, H ;
Kim, SW ;
Hwang, OY .
NEUROCHEMISTRY INTERNATIONAL, 2006, 48 (04) :255-262
[9]   Naphthazarin has a protective effect on the 1-methyl-4-phenyl-1,2,3,4-tetrahydropyridine-induced Parkinson's disease model [J].
Choi, Seon Young ;
Son, Tae Gen ;
Park, Hee Ra ;
Jang, Young Jung ;
Oh, Shin Bi ;
Jin, Bora ;
Lee, Jaewon .
JOURNAL OF NEUROSCIENCE RESEARCH, 2012, 90 (09) :1842-1849
[10]   COMPARATIVE-STUDIES ON THE MECHANISMS OF PARAQUAT AND 1-METHYL-4-PHENYLPYRIDINE (MPP+) CYTOTOXICITY [J].
DIMONTE, D ;
SANDY, MS ;
EKSTROM, G ;
SMITH, MT .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1986, 137 (01) :303-309