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Inhibition of lipopolysaccharide-inducible nitric oxide synthase and IL-1β through suppression of NF-κB activation by 3-(1′-1′-dimethyl-allyl)-6-hydroxy-7-methoxy-coumarin isolated from Ruta graveolens L.
- Source :
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European Journal of Pharmacology . Mar2007, Vol. 560 Issue 1, p69-80. 12p. - Publication Year :
- 2007
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Abstract
- Abstract: The Ruta graveolens L. plant is used in traditional medicine to treat a large number of diseases. The methanol (50%) extract of the whole plant was observed to inhibit the expression of inducible nitric oxide synthase (iNOS) and the cycloxygenase-2 (COX-2) gene in lipopolysaccharide (LPS)-induced macrophage cells (J774A.1, [Raghav, S.K., Gupta, B., Agrawal, C., Goswami, K., Das, H.R., 2006b. Anti-inflammatory effect of Ruta graveolens L. in murine macrophage cells. J. Ethnopharmacol. 104, 234–239]). The effect of whole plant extract on the expression of other pro-inflammatory genes such as tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), IL-12, interferon-γ (IFN-γ) and the activation of nuclear factor-kB (NF-κB) were investigated in LPS stimulated macrophage cells. An active compound was isolated from this methanol extract by further solvent fractionation and reverse phase high performance liquid chromatography (RP-HPLC). The purified compound was identified as 3-(1′-1′-dimethyl-allyl)-6-hydroxy-7-methoxy-coumarin having IUPAC nomenclature of 6-hydroxy-7-methoxy-3-(2-methyl but-3-en-2yl)-2H-chromen-2-one by ESI-MS, MALDI, FT-IR and NMR. Effect of this purified compound was assessed on iNOS, COX-2 and various pro-inflammatory cytokine genes and was observed to inhibit both the protein and mRNA expression of iNOS and IL-1β in LPS challenged macrophages. Electrophoretic mobility shift assay (EMSA) and Western blot analyses indicated that the plant extract and the isolated active compound blocked the LPS-induced activation of NF-κB through the prevention of inhibitor-kB (IkB) degradation. The purified compound also showed the anti-oxidant activity. The active compound at a dose of 40 mg/kg body weight was observed to inhibit the iNOS and IL-1β gene expression significantly in endotoxin-induced inflammatory model of BALB/c mice. The low level of nitric oxide production was also observed in the sera of compound treated mice. The normal behavioral condition in LPS challenged BALB/c mice was noticed when these were treated with active compound. [Copyright &y& Elsevier]
- Subjects :
- *COMMON rue
*HIGH performance liquid chromatography
*CYTOKINES
*GENE expression
Subjects
Details
- Language :
- English
- ISSN :
- 00142999
- Volume :
- 560
- Issue :
- 1
- Database :
- Academic Search Index
- Journal :
- European Journal of Pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 24218963
- Full Text :
- https://doi.org/10.1016/j.ejphar.2007.01.002