کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2200240 | 1551275 | 2016 | 9 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Novel compound from Polygonum multiflorum inhibits inflammatory response in LPS-stimulated microglia by upregulating AMPK/Nrf2 pathways Novel compound from Polygonum multiflorum inhibits inflammatory response in LPS-stimulated microglia by upregulating AMPK/Nrf2 pathways](/preview/png/2200240.png)
• CRPE55IB inhibits LPS induced neuroinflammatory response in microglia.
• CRPE55IB inhibits LPS-induced NF-κB activation in microglia.
• Nrf2 mediates the anti-neuroinflammation of CRPE55IB in microglia.
• AMPK mediates the anti-neuroinflammatory effects of CRPE55IB in microglia.
Polygonum multiflorum extracts are known to improve memory and learning ability, and have neuroprotective and anti-aging activity. However, its function and the underlying mechanisms in neuroinflammation-mediated neurodegenerative disease remain poorly understood. In the present study, we investigated the anti-neuroinflammatory effects of several compounds from P. multiflorum, and found a novel compound, CRPE55IB. The CRPE55IB-induced suppression of NO and PGE2 production correlated with inhibition of iNOS and COX-2 protein expression and promoter activity in lipopolysaccharide (LPS)-stimulated microglia. CRPE55IB also reduced the production of pro-inflammatory cytokines (TNF-α and IL-6) induced by LPS. Furthermore, investigation of the molecular mechanism indicated that CRPE55IB inhibited LPS-induced NF-κB activation by inactivating phosphorylation of IKKα/β, and phosphorylation and degradation of IκBα. We further found that CRPE55IB inhibited the phosphorylation of ERK and JNK at a lower concentration than that for p38 MAPK. Further experiments revealed that CRPE55IB treatment considerably increased the activation of Nrf2/ARE, and the expression of its target genes, including HO-1 and NQO1. Moreover, the Knockdown of Nrf2, HO-1, and NQO1 by siRNA abrogated the inhibitory effect of CRPE55IB on iNOS and COX-2 promoter activity. CRPE55IB also induced phosphorylation of AMPK/LKB/CaMKII in microglia. Analysis using a specific inhibitor of AMPK demonstrated that AMPK activation was involved in CRPE55IB-induced HO-1 and NQO1 expression. In addition, the CRPE55IB-induced anti-neuroinflammatory effect was abrogated by a specific inhibitor of AMPK, indicating the important role of AMPK in CRPE55IB-induced anti-neuroinflammation. Collectively, these results demonstrate that CRPE55IB exerts anti-neuroinflammatory effects against LPS via the Nrf2/AMPK signaling pathways.
Journal: Neurochemistry International - Volume 100, November 2016, Pages 21–29