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Inhibition of Double-Stranded RNA-Induced Inducible Nitric Oxide Synthase Expression by Fraxinellone and Sauchinone in Murine Microglia

Cited 18 time in Web of Science Cited 18 time in Scopus
Authors

Lee, Chang-Seok; Won, Cheolhee; Yoo, Hyouna; Yi, Eun Hee; Maeng, Jung Woo; Ye, Sang-Kyu; Chung, Myung-Hee; Sung, Sang Hyun; Cho, Yuri

Issue Date
2009-11
Publisher
PHARMACEUTICAL SOC JAPAN
Citation
BIOLOGICAL & PHARMACEUTICAL BULLETIN; Vol.32 11; 1870-1874
Keywords
double-stranded RNAinducible nitric oxide synthase, STAT, c-Jun N-terminal kinase, fraxinellone, sauchinoneSTATc-Jun N-terminal kinase
Abstract
Fraxinellone and sauchinone, isolated from natural substance, are known to have an anti-inflammatory effect in inflammatory conditions. However, the anti-inflammatory actions of these compounds have been insufficiently demonstrated in viral-induced neuroinflammation. A viral component (double-stranded (ds)RNA) triggers a toll-like receptor 3-dependent inflammatory response that stimulates pro-inflammatory mediators in the brain. In present study, we initially examined the biological effects of fraxinellone and sauchinone on anti-inflammatory actions in dsRNA-stimulated microglia. Both compounds inhibited dsRNA-induced inducible nitric oxide synthase (NOS) expression, a major pro-inflammatory enzyme. 16 demonstrate the mechanism of inhibitory effect on NOS expression, we further examined file signaling pathway induced by dsRNA in microglia. Our data show that dsRNA promotes the expression of signal transducers and activators of transcription (STAT)1/3 identified as major inflammatory transcription factors as well as activates c-Jun N-terminal kinase (JNK) in an early time. Moreover, both compounds suppressed activation of JNK-STAT1/3 signaling pathway. These results suggest that an anti-inflammatory effect by fraxinellone and sauchinone is mediated via blockade of the JNK-STAT1/3-iNOS signaling pathway in viral-infected microglia.
ISSN
0918-6158
Language
English
URI
https://hdl.handle.net/10371/78095
DOI
https://doi.org/10.1248/bpb.32.1870
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