Lycopodium Attenuates Loss of Dopaminergic Neurons by Suppressing Oxidative Stress and Neuroinflammation in a Rat Model of Parkinson’s Disease

Molecules

Sheikh Azimullah¹  RichardL. Jayaraj¹  Abdu Adem¹  ShreeshK. Ojha¹  Rami Beiram¹  MohamedFizur Nagoor Meeran¹  FakhreyaYousuf Jalal¹ 

[1] Department of Pharmacology and Therapeutics, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates;

关键词: lycopodium;    matrix metalloproteinase;    neuroinflammation;    neurodegeneration;    oxidative stress;    Parkinson’s disease;   

DOI  :  10.3390/molecules24112182

来源: DOAJ

【 摘 要 】

Parkinson’s disease, a chronic, age related neurodegenerative disorder, is characterized by a progressive loss of nigrostriatal dopaminergic neurons. Several studies have proven that the activation of glial cells, presence of alpha-synuclein aggregates, and oxidative stress, fuels neurodegeneration, and currently there is no definitive treatment for PD. In this study, a rotenone-induced rat model of PD was used to understand the neuroprotective potential of Lycopodium (Lyc), a commonly-used potent herbal medicine. Immunohistochemcial data showed that rotenone injections significantly increased the loss of dopaminergic neurons in the substantia nigra, and decreased the striatal expression of tyrosine hydroxylase. Further, rotenone administration activated microglia and astroglia, which in turn upregulated the expression of α-synuclein, pro-inflammatory, and oxidative stress factors, resulting in PD pathology. However, rotenone-injected rats that were orally treated with lycopodium (50 mg/kg) were protected against dopaminergic neuronal loss by diminishing the expression of matrix metalloproteinase-3 (MMP-3) and MMP-9, as well as reduced activation of microglia and astrocytes. This neuroprotective mechanism not only involves reduction in pro-inflammatory response and α-synuclein expression, but also synergistically enhanced antioxidant defense system by virtue of the drug’s multimodal action. These findings suggest that Lyc has the potential to be further developed as a therapeutic candidate for PD.

【 授权许可】

Unknown