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

被引：127

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

来源：

NEUROTOXICITY RESEARCH | 2019年 / 36卷 / 03期

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

页码：452 / 462

页数：11

共 63 条

[1] Interleukin-10 protects against inflammation-mediated degeneration of dopaminergic neurons in substantia nigra [J].