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Molecules 2018, 23(12), 3196; https://doi.org/10.3390/molecules23123196

Pseudane-VII Regulates LPS-Induced Neuroinflammation in Brain Microglia Cells through the Inhibition of iNOS Expression

1
Department of Life Science, Immunology Research Lab, BK21-plus Research Team for Bioactive Control Technology, College of Natural Sciences, Chosun University, Dong-gu, Gwangju 61452, Korea
2
Department of Pharmacy, College of Pharmacy, Molecular Inflammation Research Center for Aging Intervention, Pusan National University, Busan 46241, Korea
3
Biocenter, GyeonggidoBusiness & Science Accelerator (GBSA), Suwon, Gyeonggi-do 16229, Korea
These authors contributed equally to this work.
*
Authors to whom correspondence should be addressed.
Received: 7 November 2018 / Revised: 28 November 2018 / Accepted: 29 November 2018 / Published: 4 December 2018
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Abstract

We previously isolated pseudane-VII from the secondary metabolites of Pseudoalteromonas sp. M2 in marine water, and demonstrated its anti-inflammatory efficacy on macrophages. However, the molecular mechanism by which pseudane-VII suppresses neuroinflammation has not yet been elucidated in brain microglia. Microglia is activated by immunological stimulation or brain injury. Activated microglia secrete proinflammatory mediators which damage neurons. Neuroinflammation appears to be associated with certain neurological diseases, including Parkinson’s disease and Alzheimer’s disease. Natural compounds that suppress microglial inflammatory responses could potentially be used to prevent neurodegenerative diseases or slow their progression. In the present study, we found that pseudane-VII suppresses neuroinflammation in lipopolysaccaride (LPS)-stimulated BV-2 microglial cells and brain. Pseudane-VII was shown to inhibit the LPS-stimulated NO, ROS production and the expression of iNOS and COX-2. To identify the signaling pathway targeted by pseudane-VII, we used western blot analysis to assess the LPS-induced phosphorylation state of p38, ERK1/2, JNK1/2, and nuclear factor-kappaB (NF-κB). We found that pseudane-VII attenuated LPS-induced phosphorylation of MAPK and NF-κB. Moreover, administration of pseudane-VII in mice significantly reduced LPS-induced iNOS expression and microglia activation in brain. Taken together, our findings suggest that pseudane-VII may represent a potential novel target for treatment for neurodegenerative diseases. View Full-Text
Keywords: Pseudoalteromonas sp. M2; pseudane-VII; anti-neuroinflammation activity; microglia Pseudoalteromonas sp. M2; pseudane-VII; anti-neuroinflammation activity; microglia
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
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Kim, M.E.; Jung, I.; Na, J.Y.; Lee, Y.; Lee, J.; Lee, J.S.; Lee, J.S. Pseudane-VII Regulates LPS-Induced Neuroinflammation in Brain Microglia Cells through the Inhibition of iNOS Expression. Molecules 2018, 23, 3196.

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