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Research
Feng Zhang
Zunyi Medical University
Corresponding Author
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This work is licensed under a CC BY 4.0 License. Read Full License
Background: Neuroinflammation plays a crucial role in the pathological process of Parkinson's disease (PD). Nod-like receptor protein 3 (NLRP3) inflammasome was highly located in microglia and involved in the process of neuroinflammation. Activation of NLRP3 inflammasome has been confirmed to contribute to the progression of PD. Thus, inhibition of NLRP3 inflammasomes activation could be an important breakthrough point in PD drug therapy. Ellagic acid (EA) is a natural polyphenol that has been widely found in soft fruits, nuts and other plant tissues with various anti-inflammatory and anti-oxidant properties. However, the mechanisms underlying EA-mediated anti-inflammatory and neuroprotection have not been fully elucidated.
Methods: In this study, lipopolysaccharide (LPS)-induced rat dopamine (DA) neuronal damage model was performed to determine the effects of EA on the protection of DA neurons. Furthermore, DA neuron MN9D cell line and microglia BV-2 cell line were employed to explore whether EA-mediated neuroprotection was through an NLRP3-dependent mechanism.
Results: EA ameliorated LPS-induced DA neuronal loss in rat substantia nigra. Furtherly, inhibition of microglial NLRP3 inflammasome signaling activation was involved in EA-generated neuroprotection, as evidenced by the following observations. First, EA reduced NLRP3 inflammasome signaling activation in microglia and the subsequent pro-inflammatory cytokines excretion. In addition, EA-mediated anti-neuroinflammation and further DA neuroprotection from LPS-induced neurotoxicity was not shown upon microglial NLRP3 siRNA treatment.
Conclusions: This study demonstrated EA has a profound effect on protecting DA neurons against LPS-induced neurotoxicity via the suppression of microglial NLRP3 inflammasome signaling activation.
Keywords
Parkinson’s disease, Microglia, Inflammasome, Ellagic acid, Neuroprotection
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This is a preprint. It has not completed peer review.
Research
Feng Zhang
Zunyi Medical University
Corresponding Author
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
History
CURRENT STATUS: Posted
Version 1
Posted 26 Nov, 2019
No community comments so far
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Neurobiology of Disease
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Background: Neuroinflammation plays a crucial role in the pathological process of Parkinson's disease (PD). Nod-like receptor protein 3 (NLRP3) inflammasome was highly located in microglia and involved in the process of neuroinflammation. Activation of NLRP3 inflammasome has been confirmed to contribute to the progression of PD. Thus, inhibition of NLRP3 inflammasomes activation could be an important breakthrough point in PD drug therapy. Ellagic acid (EA) is a natural polyphenol that has been widely found in soft fruits, nuts and other plant tissues with various anti-inflammatory and anti-oxidant properties. However, the mechanisms underlying EA-mediated anti-inflammatory and neuroprotection have not been fully elucidated.
Methods: In this study, lipopolysaccharide (LPS)-induced rat dopamine (DA) neuronal damage model was performed to determine the effects of EA on the protection of DA neurons. Furthermore, DA neuron MN9D cell line and microglia BV-2 cell line were employed to explore whether EA-mediated neuroprotection was through an NLRP3-dependent mechanism.
Results: EA ameliorated LPS-induced DA neuronal loss in rat substantia nigra. Furtherly, inhibition of microglial NLRP3 inflammasome signaling activation was involved in EA-generated neuroprotection, as evidenced by the following observations. First, EA reduced NLRP3 inflammasome signaling activation in microglia and the subsequent pro-inflammatory cytokines excretion. In addition, EA-mediated anti-neuroinflammation and further DA neuroprotection from LPS-induced neurotoxicity was not shown upon microglial NLRP3 siRNA treatment.
Conclusions: This study demonstrated EA has a profound effect on protecting DA neurons against LPS-induced neurotoxicity via the suppression of microglial NLRP3 inflammasome signaling activation.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
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