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Inhibition of lipopolysaccharide-inducible nitric oxide synthase and IL-1beta through suppression of NF-kappaB activation by 3-(1'-1'-dimethyl-allyl)-6-hydroxy-7-methoxy-coumarin isolated from Ruta graveolens L.
Eur J Pharmacol. 2007 Mar 29; 560(1):69-80.EJ

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-alpha (TNF-alpha), interleukin-1beta (IL-1beta), IL-12, interferon-gamma (IFN-gamma) and the activation of nuclear factor-kB (NF-kappaB) 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-1beta 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-kappaB 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-1beta 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.

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Authors+Show Affiliations

Raghav SK
Proteomics and Structural Biology Division, Institute of Genomics and Integrative Biology, Delhi University Campus, Mall Road, Delhi-110 007, India.
Gupta B
No affiliation info available
Shrivastava A
No affiliation info available
Das HR
No affiliation info available

MeSH

AnimalsAnti-Inflammatory AgentsBlotting, WesternChromatography, High Pressure LiquidCoumarinsCytokinesDisease Models, AnimalElectrophoretic Mobility Shift AssayGene ExpressionI-kappa B ProteinsInterleukin-1betaLipopolysaccharidesMacrophagesMiceMice, Inbred BALB CNF-kappa BNitric OxideNitric Oxide Synthase Type IIPhytotherapyPlant ExtractsRuta

Pub Type(s)

Journal Article

Language

eng

PubMed ID

17292351

Citation

Raghav, Sunil Kumar, et al. "Inhibition of Lipopolysaccharide-inducible Nitric Oxide Synthase and IL-1beta Through Suppression of NF-kappaB Activation By 3-(1'-1'-dimethyl-allyl)-6-hydroxy-7-methoxy-coumarin Isolated From Ruta Graveolens L." European Journal of Pharmacology, vol. 560, no. 1, 2007, pp. 69-80.
Raghav SK, Gupta B, Shrivastava A, et al. Inhibition of lipopolysaccharide-inducible nitric oxide synthase and IL-1beta through suppression of NF-kappaB activation by 3-(1'-1'-dimethyl-allyl)-6-hydroxy-7-methoxy-coumarin isolated from Ruta graveolens L. Eur J Pharmacol. 2007;560(1):69-80.
Raghav, S. K., Gupta, B., Shrivastava, A., & Das, H. R. (2007). Inhibition of lipopolysaccharide-inducible nitric oxide synthase and IL-1beta through suppression of NF-kappaB activation by 3-(1'-1'-dimethyl-allyl)-6-hydroxy-7-methoxy-coumarin isolated from Ruta graveolens L. European Journal of Pharmacology, 560(1), 69-80.
Raghav SK, et al. Inhibition of Lipopolysaccharide-inducible Nitric Oxide Synthase and IL-1beta Through Suppression of NF-kappaB Activation By 3-(1'-1'-dimethyl-allyl)-6-hydroxy-7-methoxy-coumarin Isolated From Ruta Graveolens L. Eur J Pharmacol. 2007 Mar 29;560(1):69-80. PubMed PMID: 17292351.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Inhibition of lipopolysaccharide-inducible nitric oxide synthase and IL-1beta through suppression of NF-kappaB activation by 3-(1'-1'-dimethyl-allyl)-6-hydroxy-7-methoxy-coumarin isolated from Ruta graveolens L. AU - Raghav,Sunil Kumar, AU - Gupta,Bhawna, AU - Shrivastava,Anju, AU - Das,Hasi Rani, Y1 - 2007/01/19/ PY - 2006/11/16/received PY - 2007/01/06/revised PY - 2007/01/10/accepted PY - 2007/2/13/pubmed PY - 2007/5/16/medline PY - 2007/2/13/entrez SP - 69 EP - 80 JF - European journal of pharmacology JO - Eur J Pharmacol VL - 560 IS - 1 N2 - 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-alpha (TNF-alpha), interleukin-1beta (IL-1beta), IL-12, interferon-gamma (IFN-gamma) and the activation of nuclear factor-kB (NF-kappaB) 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-1beta 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-kappaB 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-1beta 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. SN - 0014-2999 UR - https://www.unboundmedicine.com/medline/citation/17292351/Inhibition_of_lipopolysaccharide_inducible_nitric_oxide_synthase_and_IL_1beta_through_suppression_of_NF_kappaB_activation_by_3__1'_1'_dimethyl_allyl__6_hydroxy_7_methoxy_coumarin_isolated_from_Ruta_graveolens_L_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0014-2999(07)00013-1 DB - PRIME DP - Unbound Medicine ER -
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