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 (iNOS) expression, a major pro-inflammatory enzyme. To demonstrate the mechanism of inhibitory effect on iNOS expression, we further examined the 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.
journal_name
Biol Pharm Bulljournal_title
Biological & pharmaceutical bulletinauthors
Lee CS,Won C,Yoo H,Yi EH,Cho Y,Maeng JW,Sung SH,Ye SK,Chung MHdoi
10.1248/bpb.32.1870subject
Has Abstractpub_date
2009-11-01 00:00:00pages
1870-4issue
11eissn
0918-6158issn
1347-5215pii
JST.JSTAGE/bpb/32.1870journal_volume
32pub_type
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