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.
Highlights
Neuroinflammation is associated with neurodegenerative diseases, including amyotrophic lateral sclerosis, multiple sclerosis, Parkinson’s disease, and Alzheimer’s disease [1]
These results indicate that the anti-neuroinflammatory effects of pseudane-VII are mediated pseudane-VII are mediated via the regulation of IL-1β production
Discussion of evidence confirm that neuroinflammation wasinvolved closely in involved in the SeveralSeveral lines oflines evidence confirm that neuroinflammation was closely the pathogenesis pathogenesis of neurodegenerative such as Alzheimer’s and Parkinson’s of neurodegenerative disease, such asdisease, Alzheimer’s and Parkinson’s diseasedisease
Summary
Neuroinflammation is associated with neurodegenerative diseases, including amyotrophic lateral sclerosis, multiple sclerosis, Parkinson’s disease, and Alzheimer’s disease [1]. Microglia presents a series of changes in morphology and function after activated by an acute insult to the CNS [4]. Upon activation by brain injury or inflammatory activated by an acute insult to the CNS [4]. The production and accumulation of these inflammatory mediators could mediators could further regulate neuroinflammatory response, and injure neurons [7,8]. TNF-α, which are involved in inflammatory responses of the CNS [10].induction. This study, we investigate whether pseudane-VII has anti-neuroinflammatory properties in. We investigate whether pseudane-VII has anti-neuroinflammatory properties in vitro vitro and in vivo, and whether this compound regulates the expression of inflammatory factors, andincluding in vivo, and whether this compound regulates the expression of inflammatory factors, including.
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