Abstract
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.
Highlights
Parkinson’s disease (PD), the second most common neurodegenerative disease followingAlzheimer’s, affects 1–3% of population older than 50 [1,2]
PD is characterized by loss of dopaminergic neurons, evidence suggests an early alteration of cholinergic neurotransmission in PD brain
Anticholinergic medications such as trihexyphenidyl, benztropine, orphenadrine, procyclidine, and biperidenare are used for the symptomatic treatment of PD [30]
Summary
Alzheimer’s, affects 1–3% of population older than 50 [1,2]. This progressive neurodegenerative disease is characterized by selective loss of dopaminergic neurons in the Substantia nigra pars compacta and a subsequent decrease in dopamine levels in the striatum (caudate and putamen) [3,4]. The etiopathogenesis of PD involves alteration in antioxidant defense and oxidative stress, following subsequent inflammation-mediated dopa-minergic neurodegeneration initiated by activation of microglia and astrocytes. Recent studies have identified potential neuroinflammatory factors, such as Matrix metalloproteinase (MMP) and α-synuclein as important modulators of microglia [10,11,12]. To counteract these, natural drugs with robust anti-oxidant and anti-inflammatory properties would help to guard dopaminergic neurons, and alleviate disease progression
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