| In vivo: |
| Eur J Pharmacol. 2007 Mar 8;558(1-3):185-93. | | Anti-inflammatory activities of ent-16alphaH,17-hydroxy-kauran-19-oic acid isolated from the roots of Siegesbeckia pubescens are due to the inhibition of iNOS and COX-2 expression in RAW 264.7 macrophages via NF-kappaB inactivation.[Pubmed: 17207792] | To isolate the anti-inflammatory components in Siegesbeckia pubescens root, we performed activity-guided fractionation using a carrageenan-induced edema rat model.
METHODS AND RESULTS:
Antinociceptive effects were followed using acetic acid-induced abdominal constriction and hot plate tests in mice. Chloroform extract was subjected to silica gel and octadesyl silane (ODS) column chromatography, and a diterpene was isolated which was identified as ent-16alphaH,17-hydroxy-kauran-19-oic acid (Siegeskaurolic acid). Pretreatment with Siegeskaurolic acid (20 or 30 mg/kg/day, p.o.) exhibited anti-inflammatory and antinociceptive effects in these animal models. To investigate the mechanisms underlying this anti-inflammatory action, we investigated the effect of Siegeskaurolic acid on lipopolysaccharide (LPS)-induced responses in a murine macrophage cell line, RAW 264.7. Siegeskaurolic acid was found to significantly inhibit the productions of nitric oxide (NO), prostaglandin E(2) (PGE(2)), and tumor necrosis factor-alpha (TNF-alpha). Consistent with these findings, inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) proteins, and iNOS, COX-2, and TNF-alpha mRNAs were found to be inhibited by Siegeskaurolic acid. Furthermore, Siegeskaurolic acid inhibited the nuclear factor-kappaB (NF-kappaB) activation induced by LPS, and this was associated with the prevention of inhibitor kappaB degradation (I kappaB), and subsequently with decreased nuclear p65 and p50 protein levels.
CONCLUSIONS:
Taken together, our data indicate that the anti-inflammatory and antinociceptive properties of Siegeskaurolic acid may be due to iNOS, COX-2 and TNF-alpha inhibition via the down-regulation of NF-kappaB binding activity. |
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