Anti-inflammatory Activity of Ursolic Acid in MPTP-Induced Parkinsonian Mouse Model

被引:126
作者
Rai, Sachchida Nand [1 ]
Zahra, Walia [1 ]
Sen Singh, Saumitra [1 ]
Birla, Hareram [1 ]
Keswani, Chetan [1 ]
Dilnashin, Hagera [1 ]
Rathore, Aaina Singh [1 ]
Singh, Rajan [1 ]
Singh, Rakesh K. [1 ]
Singh, Surya Pratap [1 ]
机构
[1] Banaras Hindu Univ, Inst Sci, Dept Biochem, Varanasi 221005, Uttar Pradesh, India
关键词
Parkinson's disease; Ursolic acid; MPTP; Neuroinflammation; IMPROVES NEUROBEHAVIORAL ACTIVITY; NIGRAL DOPAMINERGIC-NEURONS; KAPPA-B ACTIVATION; NIGROSTRIATAL TISSUE; BEHAVIORAL DEFICITS; OXIDATIVE STRESS; OLEANOLIC ACID; MICROGLIA; DISEASE; DEGENERATION;
D O I
10.1007/s12640-019-00038-6
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Neuroinflammation plays an important role in the progression of Parkinson's disease (PD) and hence may represent a target for treatment. The drugs used currently for PD only provide symptomatic relief and have adverse effects in addition to their inability in preventing degeneration of neurons. Flavonoids show potent antioxidant and anti-inflammatory activities which is very valuable for the health of human beings. Thus, in the present study, we have tried to explore the anti-inflammatory activity of orally given ursolic acid (UA) (25 mg/kg bwt), a pentacyclic triterpenoid in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-intoxicated mouse model. Significant severe oxidative stress and biochemical alterations have been seen in Parkinsonian mice after MPTP intoxication. Whereas, UA administration has significantly rescued the harmful consequence of MPTP intoxication. Ionized calcium-binding adaptor molecule 1 (Iba1), tumor necrosis factor-alpha (TNF-alpha), and nuclear transcription factor-kappa B (NF-kappa B) were seen to be altered in the substantia nigra pars compacta (SNpc) of MPTP-intoxicated mice through immunohistochemical studies. The changes in the expression level of these parameters primarily suggest increased inflammatory responses in MPTP-intoxicated mice as compared with the control. However, UA have significantly reduced these inflammatory parameters (Iba1 and TNF-alpha) along with transcription factor NF-kappa B, which regulates these inflammatory parameters and thus have inhibited MPTP-induced neuroinflammation. The immunoreactivity of tyrosine hydroxylase (TH) was considerably increased by UA treatment in the SNpc of Parkinsonian mice. The neuroinflammation and neurodegeneration along with impairments in biochemical and behavioral parameters were found to be reversed on treatment with UA. Thus, UA has shown potent anti-inflammatory activity by preventing the degeneration of dopaminergic neurons from MPTP-induced Parkinsonian mice.
引用
收藏
页码:452 / 462
页数:11
相关论文
共 63 条
[31]   Presence of reactive microglia in monkey substantia nigra years after 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine administration [J].
McGeer, PL ;
Schwab, C ;
Parent, A ;
Doudet, D .
ANNALS OF NEUROLOGY, 2003, 54 (05) :599-604
[32]   Enhanced neuroprotective effect by combination of bromocriptine and Hypericum perforatum extract against MPTP-induced neurotoxicity in mice [J].
Mohanasundari, M. ;
Srinivasan, M. S. ;
Sethupathy, S. ;
Sabesan, M. .
JOURNAL OF THE NEUROLOGICAL SCIENCES, 2006, 249 (02) :140-144
[33]  
More SV, 2013, CNS NEUROL DISORD-DR, V12, P680
[34]   LEVELS OF GLUTATHIONE, GLUTATHIONE REDUCTASE AND GLUTATHIONE S-TRANSFERASE ACTIVITIES IN RAT LUNG AND LIVER [J].
MORON, MS ;
DEPIERRE, JW ;
MANNERVIK, B .
BIOCHIMICA ET BIOPHYSICA ACTA, 1979, 582 (01) :67-78
[35]   Ursocholanic acid rescues mitochondrial function in common forms of familial Parkinson's disease [J].
Mortiboys, Heather ;
Aasly, Jan ;
Bandmann, Oliver .
BRAIN, 2013, 136 :3038-3050
[36]   Ferulic acid pretreatment mitigates MPTP-induced motor impairment and histopathological alterations in C57BL/6 mice [J].
Nagarajan, Sangeetha ;
Chellappan, David Raj ;
Chinnaswamy, Prabu ;
Thulasingam, Senthilkumar .
PHARMACEUTICAL BIOLOGY, 2015, 53 (11) :1591-1601
[37]  
Nagatsu T, 2000, J NEURAL TRANSM-SUPP, P143
[38]   CHARACTERIZATION OF URSOLIC ACID AS A LIPOXYGENASE AND CYCLOOXYGENASE INHIBITOR USING MACROPHAGES, PLATELETS AND DIFFERENTIATED HL-60 LEUKEMIC-CELLS [J].
NAJID, A ;
SIMON, A ;
COOK, J ;
CHABLERABINOVITCH, H ;
DELAGE, C ;
CHULIA, AJ ;
RIGAUD, M .
FEBS LETTERS, 1992, 299 (03) :213-217
[39]   The Role of Inflammatory and Oxidative Stress Mechanisms in the Pathogenesis of Parkinson's Disease: Focus on Astrocytes [J].
Niranjan, Rituraj .
MOLECULAR NEUROBIOLOGY, 2014, 49 (01) :28-38
[40]   ASSAY FOR LIPID PEROXIDES IN ANIMAL-TISSUES BY THIOBARBITURIC ACID REACTION [J].
OHKAWA, H ;
OHISHI, N ;
YAGI, K .
ANALYTICAL BIOCHEMISTRY, 1979, 95 (02) :351-358