Abstract
Hyperactivation of microglia, the resident innate immune cells of the central nervous system, exacerbates various neurodegenerative disorders, including Parkinson's disease (PD). Parkinson's disease is generally characterized by a severe loss of dopaminergic neurons in the nigrostriatal pathway, with substantial neuroinflammation and motor deficits. This was experimentally replicated in animal models, using neurotoxins, i.e., LPS (lipopolysaccharides) and MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine). Salicornia europaea L. (SE) has been used as a dietary supplement in Korea and Europe for several years, due to its nutritional and therapeutic value. In this study, we intend to investigate the antineuroinflammatory and anti-PD-like effects of the bioactive fraction/candidate of the SE extract. Initially, we screened various fractions of SE extract using an in vitro antioxidant assay. The optimal fraction was investigated for its in vitro antineuroinflammatory potential in LPS-stimulated BV-2 microglial cells and in vivo anti-PD-like potential in MPTP-intoxicated mice. Subsequently, to identify the potential candidate responsible for the elite therapeutic potential of the optimal fraction, we conducted antioxidant activity-guided isolation and purification; the bioactive candidate was structurally characterized using nuclear magnetic resonance spectroscopy and chromatographic techniques and further investigated for its in vitro antioxidative and antineuroinflammatory potential. The results of our study indicate that SE-EA and its bioactive candidate, Irilin B, effectively alleviate the deleterious effect of microglia-mediated neuroinflammation and promote antioxidative effects. Thus, they exhibit potential as therapeutic candidates against neuroinflammatory and oxidative stress-mediated PD-like neurodegenerative complications.
Highlights
Parkinson’s disease (PD), the second most commonly reported neurodegenerative disease (NDD), is clinically characterized by the progressive loss of dopaminergic neurons in the basal ganglia regions (i.e., precisely at the substantia nigra pars compacta (SNpc) and striatum (STR)) [1, 2]
The immunohistochemical post-mortem reports on the brains of PD patients show that the brains exhibit substantial expression of heme oxygenase (HO)-1-positive stains, which indicates the role of heme oxygenase-1 (HO-1) in PD pathogenesis [9]
Under the diseased pathological conditions of NDDs, infection and alteration in the microenvironmental factors have been reported to dynamically participate in the hyperactivation of microglial cells, and it results in neuronal cell-death cascades which mediate disease progression [38, 39]
Summary
Parkinson’s disease (PD), the second most commonly reported neurodegenerative disease (NDD), is clinically characterized by the progressive loss of dopaminergic neurons in the basal ganglia regions (i.e., precisely at the substantia nigra pars compacta (SNpc) and striatum (STR)) [1, 2]. In the case of PD, the ROS insult, protein aggregate accumulation, and mitochondrial dysfunction-mediated stimulation of glial cells potentially activate the canonical nuclear factor kappa-light-chain-enhancer (NF-κB) and subsequent mitogen-activated protein kinase (MAPK) pathways This event leads to release of several proinflammatory cytokines, i.e., tumour necrosis factor (TNF-α), interleukins (IL-1β and IL-6), and proinflammatory mediators, i.e., nitric oxide (NO), inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2) [15, 16]. These cascades eventually result in dopaminergic cell death and neuronal loss in the nigrostriatal regions, as has been observed in postmortem brain reports of PD patients [17, 18]. Several studies have adapted these models to investigate the antiPD-like therapeutic potential of various bioactive candidates [21, 23, 24]
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