| 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. |
|
Cell. 2018 Jan 11;172(1-2):249-261.e12. doi: 10.1016/j.cell.2017.12.019.IF=36.216(2019)
Cell Metab. 2020 Mar 3;31(3):534-548.e5. doi: 10.1016/j.cmet.2020.01.002.IF=22.415(2019)
Mol Cell. 2017 Nov 16;68(4):673-685.e6. doi: 10.1016/j.molcel.2017.10.022.IF=14.548(2019)
ACS Nano. 2018 Apr 24;12(4): 3385-3396. doi: 10.1021/acsnano.7b08969.IF=13.903(2019)
Nature Plants. 2016 Dec 22;3: 16206. doi: 10.1038/nplants.2016.205.IF=13.297(2019)
Sci Adv. 2018 Oct 24;4(10): eaat6994. doi: 10.1126/sciadv.aat6994.IF=12.804(2019)
