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DHARA is an online index of articles on Ayurveda published in research journals worldwide.
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The Journal of Pharmacy and Pharmacology
2007
Apr
;
(4)
:0
Suppression of the NF-kappaB signalling pathway by ergolide, sesquiterpene lactone, in HeLa cells.
Chun JK
,
Seo DW
,
Ahn SH
,
Park JH
,
You JS
,
Lee CH
,
Lee JC
,
Kim YK
,
Han JW
Abstract
We have previously reported that ergolide, a sesquiterpene lactone isolated from Inula britannica, suppresses inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression by inhibiting nuclear factor-kappaB (NF-kappaB) in RAW 264.7 macrophages. In this study, we show that ergolide suppresses the DNA binding activity of NF-kappaB and nuclear translocation of NF-kappaB p65 subunit, leading to the inhibition of NF-kappaB-dependent gene transcription in 12-O-tetradecanoylphorbol 13acetate (TPA)-stimulated HeLa cells. We also show that ergolide decreases the degradation and phosphorylation of IkappaB, an inhibitory protein of NF-kappaB, and this effect is accompanied by a simultaneous reduction of IkappaB kinase (IKK) activity. However, ergolide does not inhibit in-vitro IKK activity directly, suggesting the possible involvement of upstream IKK kinases in the regulation of NF-kappaB activation. Furthermore, ergolide-mediated protein kinase Calpha (PKCalpha) inhibition is involved in reduction of NF-kappaB inhibition, as demonstrated by the observation that dominant negative PKCalpha, but not p44/42 MAPK and p38 MAPK, inhibits TPA-stimulated reporter gene expression. Taken together, our results suggest that ergolide suppresses NF-kappaB activation through the inhibition of PKCalpha-IKK activity, providing insight for PKCalpha as a molecular target for anti-inflammatory drugs.
DHARA ID:
D047117
Pubmed ID:
17430640
Access to Full Paper Not Available
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