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Volume 41, Issue 6, Pages (December 2004)

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Presentation on theme: "Volume 41, Issue 6, Pages (December 2004)"— Presentation transcript:

1 Volume 41, Issue 6, Pages 926-934 (December 2004)
Curcumin inhibits NF-κB activation and reduces the severity of experimental steatohepatitis in mice  Isabelle A. Leclercq, Geoffrey C. Farrell, Christine Sempoux, Aileen dela Peña, Yves Horsmans  Journal of Hepatology  Volume 41, Issue 6, Pages (December 2004) DOI: /j.jhep Copyright © 2004 European Association for the Study of the Liver Terms and Conditions

2 Fig. 1 Effects of curcumin on hepatic morphology in mice fed the control diet and the MCD diet. Liver sections from female C57BL6/J mice fed the control diet (A), MCD diet for 10 days (C) or 4 weeks (E), control diet+curcumin (1% w/w) (B), MCD+curcumin (1% w/w) for 10 days (D) and 4 weeks (F). H&E stained, original magnification ×10. Arrows indicate necroinflammatory lesions. Journal of Hepatology  , DOI: ( /j.jhep ) Copyright © 2004 European Association for the Study of the Liver Terms and Conditions

3 Fig. 2 Effects of curcumin on collagen, KLF-6, TGFβ1 and CTGF mRNA levels in mice fed the control or the MCD diet. Hepatic type I collagen (A), TGFβ1 (B), KLF-6 (C) and CTGF (D) mRNA determined by real-time PCR (values normalised to the expression of RLP19 mRNA regarded as an internal control) in the liver of mice fed the control or MCD diet alone (open box) or the curcumin-supplemented diet (grey box). Data are mean±SD (n=5/group). *P<0.05, **P<0.01 compared with mice fed the corresponding control diet. &P<0.05 for comparison between mice fed the MCD diet and mice fed the MCD diet+curcumin. Journal of Hepatology  , DOI: ( /j.jhep ) Copyright © 2004 European Association for the Study of the Liver Terms and Conditions

4 Fig. 3 Effects of MCD diet and curcumin on NF-κB activation. (A) Representative electromobility gel shift assay using NF-κB oligonucleotide consensus binding sequence and nuclear proteins extracted from the liver of mice fed the control diet, the control diet+curcumin 1%, the MCD diet and the MCD diet+curcumin 1% for 10 days or 4 weeks. The nature of the bands was confirmed by supershift assays as described in Section 2 (not shown). NS denotes non specific band. (B) Graph representing the mean optical density of active NF-κB complex (p65:p50)±SD for n=5 per group, in duplicate in mice fed the control or the MCD diet alone (open box) or the curcumin-supplemented diet (grey box). **P<0.01, ***P<0.001 compared with mice fed the appropriate control diet. &P<0.05, &&&P<0.001 for comparison between mice fed the MCD diet and mice fed the MCD diet+curcumin at the denoted time point. Journal of Hepatology  , DOI: ( /j.jhep ) Copyright © 2004 European Association for the Study of the Liver Terms and Conditions

5 Fig. 4 Effects of curcumin on hepatic mRNA expression of pro-inflammatory genes in mice fed the control diet and the MCD diet. Hepatic mRNA levels for (A) intercellular adhesion molecule-1 (ICAM-1), (B) cyclo-oxygenase-2 (COX-2), (C) monocyte chemoattractant protein-1 (MCP-1), (D) inducible nitric oxide synthase (iNOS) and (e) cytokine-induced neutrophil chemoattractant (CINC) (E) in mice fed the control or MCD diet alone (open bars) or curcumin-supplemented diet (grey bars) for 4 weeks. mRNA levels were determined by real-time PCR and results normalised to the level of expression of RPL19 mRNA regarded as an invariant control. Data are mean±SD (n=5/group). *P<0.05, **P<0.01 compared with mice fed the corresponding control diet. &P<0.05, &&P<0.01 for comparison between mice fed the MCD diet and mice fed the MCD diet+curcumin. Journal of Hepatology  , DOI: ( /j.jhep ) Copyright © 2004 European Association for the Study of the Liver Terms and Conditions

6 Fig. 5 Curcumin does not alter MCD-diet induced activation of AP-1 or MAP kinase pathways. (A) Representative electromobility shift assay using AP-1 oligonucleotide consensus binding sequence and nuclear proteins extracted from the liver of mice fed the control diet, the control diet+curcumin 1%, the MCD diet and the MCD diet+curcumin1% (w/w) for 10 days. The nature of the band has been has been confirmed by supershift assays as described in Section 2 (not shown) and NS denotes non specific band. (B) Graph representing the mean optical density of AP-1/DNA complex±SD for n=5 per group, in duplicate in mice fed the control or the MCD diet alone (open box) or the curcumin-supplemented diet (grey box). (C) Graph representing the optical density of heme-oxygenase-1 (HO-1) protein as determined by western immunoblotting on liver homogenates (mean±SD for n=5 per group). (D) Representative western blot showing expression of total Erk 1 and 2 protein (upper panel) and their phosphorylated forms (lower panel) in the liver of mice fed the control, the MCD or the MCD diet+1% curcumin for 10 days. (E) Graph representing p-Erk-1 and p-Erk-2 as the ratio of phosphorylated protein to the total protein. *P<0.05, **P<0.01, ***P<0.001 compared with mice fed the control diet (open box). No significant difference (NS) was observed between mice fed the MCD diet with (dark grey box) or without (light grey box) curcumin 1%. Journal of Hepatology  , DOI: ( /j.jhep ) Copyright © 2004 European Association for the Study of the Liver Terms and Conditions


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