Abstract
A growing body of evidence indicates that the majority of Parkinson's disease (PD) cases are associated with microglia activation with resultant elevation of various inflammatory mediators and neuroinflammation. In this study, we investigated the effects of 2 natural molecules, quercetin and sesamin, on neuroinflammation induced by the Parkinsonian toxin 1-methyl-4-phenylpyridinium (MPP+) in a glial-neuronal system. We first established that quercetin and sesamin defend microglial cells against MPP+-induced increases in the mRNA or protein levels of 3 pro-inflammatory cytokines (interleukin-6, IL-1β and tumor necrosis factor-alpha), as revealed by real time-quantitative polymerase chain reaction and enzyme-linked immunoabsorbent assay, respectively. Quercetin and sesamin also decrease MPP+-induced oxidative stress in microglial cells by reducing inducible nitric oxide synthase protein expression as well as mitochondrial superoxide radicals. We then measured neuronal cell death and apoptosis after MPP+ activation of microglia, in a microglial (N9)-neuronal (PC12) coculture system. Our results revealed that quercetin and sesamin rescued neuronal PC12 cells from apoptotic death induced by MPP+ activation of microglial cells. Altogether, our data demonstrate that the phytoestrogen quercetin and the lignan sesamin diminish MPP+-evoked microglial activation and suggest that both these molecules may be regarded as potent, natural, anti-inflammatory compounds.
Highlights
Parkinson’s disease (PD) is a progressive, neurodegenerative disorder characterized by the loss of dopaminergic (DAergic) neurons in the substantia nigra (SN) and glial dysfunction
We measured the expression of the potent proinflammatory cytokines IL-6, IL-1β, and TNFα by room temperature (RT)-qPCR
Our present data highlight the neuroprotective properties of quercetin and sesamin, 2 natural molecules that reduce the expression of IL-6, IL-1β, and TNFα, 3 cytokines associated with neuroinflammation
Summary
Parkinson’s disease (PD) is a progressive, neurodegenerative disorder characterized by the loss of dopaminergic (DAergic) neurons in the substantia nigra (SN) and glial dysfunction. Postmortem studies have shown that microglia are activated regionally in the SN of PD patients as well as in PD animal models [4,5,6]. Resident immune cells of the brain, are activated in response to initiation factors (i.e., toxins, bacteria or viruses, pesticides, neuronal injury, etc.). These factors may trigger a self-perpetuating cycle of chronic neuroinflammation, increasing the release of inflammatory chemical substances and promoting microglia activation. The SN is the brain region with the highest density of microglial cells [7]; the neurons of this region are susceptible to microglial-mediated toxicity in vitro and in vivo [8]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
