N,N-disubstituted azines attenuate LPS-mediated neuroinflammation in microglia and neuronal apoptosis via inhibiting MAPK signaling pathways
- Authors
- Subedi, Lalita; Kwon, Oh Wook; Pak, Chaeho; Lee, Goeun; Lee, Kangwoo; Kim, Hakwon; Kim, Sun Yeou
- Issue Date
- 28-Dec-2017
- Publisher
- BMC
- Keywords
- Azine; Lipopolysaccharide; Neuroinflammation; MAPK; Apoptosis
- Citation
- BMC NEUROSCIENCE, v.18
- Journal Title
- BMC NEUROSCIENCE
- Volume
- 18
- URI
- https://scholarworks.bwise.kr/gachon/handle/2020.sw.gachon/5363
- DOI
- 10.1186/s12868-017-0399-3
- ISSN
- 1471-2202
- Abstract
- Background: Activated microglia interact with astrocytes and neuronal cells to induce neuroinflammation, which can contribute to the pathogenesis and progression of Alzheimer's and Parkinson's disease. To identify the most effective anti-neuroinflammatory agent, we designed and synthesized a family of 13 new azine derivatives and investigated their anti-neuroinflammatory activities in LPS-activated BV-2 microglial cells. Results: Out of 13 derivatives, compound 3 [4,4'-(1E, 1'E, 3E, 3'E)-3,3'-(hydrazine-1,2-diylidene) bis-(prop-1-ene-1-yl-3-ylidene) bis-(2-methoxyphenol)] exhibited excellent anti-neuroinflammatory activities (IC50 = 12.47 mu M), which protected neurons from microglia-mediated neurotoxicity. Specifically, the anti-neuroinflammatory effects of compound 3 inhibited MAPK signaling pathways through the inhibition of p38 and JNK mediated signaling and the production of pro-inflammatory cytokines, and inflammatory mediators. Additionally, compound 3 strongly exhibited neuroprotective effect by inhibiting LPS-mediated necrosis and apoptosis. Preliminary SAR analysis suggests that the presence of methoxyphenol and the substitution pattern within hydrazine may influence the anti-neuroinflammatory activity. FACS analysis also strongly supports the neuroprotective effect of compound 3. Conclusions: Based on our results, the compound 3 exhibited excellent anti-neuroinflammatory activity against LPS-activated microglia, which resulted in the inhibition of neuronal apoptosis and neuronal degeneration.
- Files in This Item
- There are no files associated with this item.
- Appears in
Collections - 약학대학 > 약학과 > 1. Journal Articles
![qrcode](https://api.qrserver.com/v1/create-qr-code/?size=55x55&data=https://scholarworks.bwise.kr/gachon/handle/2020.sw.gachon/5363)
Items in ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.