Sauchinone, a Lignan from Saururus chinensis, Suppresses iNOS Expression through the Inhibition of Transactivation Activity of ReIA of NF-κB

Anticancer Agents Research Laboratory, Korea Research Institute of Bioscience and Biotechnology, Yuseong, Daejeon, Korea.
Planta Medica (Impact Factor: 2.15). 01/2004; 69(12):1096-101. DOI: 10.1055/s-2003-45189
Source: PubMed


Sauchinone, a known lignan, was isolated from the root of Saururus chinensis as an active principle responsible for inhibiting the production of NO in LPS-stimulated RAW264.7 cells by activity-guided fractionation. Sauchinone dose-dependently inhibited not only the production of NO, but also the expression of iNOS mRNA and protein in LPS-stimulated RAW 264.7 cells. Furthermore, sauchinone prevented LPS-induced NF-kappaB activation, which is known to play a critical role in iNOS expression, assessed by a reporter assay under the control of NF-kappaB. However, an electrophoretic mobility shift assay (EMSA) demonstrated that sauchinone did not suppress the DNA-binding activity of NF-kappaB or the degradation of IkappaB-alpha induced by LPS. Further analysis revealed that transactivation activity of RelA subunit of NF-kappaB was dose-dependently suppressed in the presence of sauchinone. Taken together, our results suggested that sauchinone could inhibit production of NO in LPS-stimulated RAW264.7 cells through the suppression of NF-kappaB by inhibiting transactivation activity of RelA subunit.

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    • "CD4+ Th cells stimulated with anti-CD3 and anti-CD28 were induced to differentiate into Th1, Th2, and Th17 cells and subsequently treated with various amounts of sauchinone at day 2 of Th cell differentiation. Although sauchinone is known to inhibit NF-kB p65 activity and affect NF-kB-mediated cell proliferation [6] [7], Th cell proliferation and expansion upon TCR stimulation were not affected by the addition of indicated amounts of sauchinone during Th cell differentiation. Sauchinone had no significant effect on both Th1 and Th17 cell development (Fig. 4A and B), suggesting indirect function of sauchinone on the suppression of IL-17 in the inflammatory lung. "
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    ABSTRACT: Sauchinone, a lignan compound isolated from the root of Saururus chinensis, has been recently demonstrated to exhibit anti-inflammatory activity via the suppression of NF-kB p65 activity in vitro. In an effort to evaluate the in vivo anti-inflammatory function of sauchinone, we have evaluated the effects of sauchinone on allergen-induced airway inflammation using a murine model of allergic asthma. We observed that marked eosinophilic and lymphocyte infiltration in the BAL fluid were suppressed to a significant degree by sauchinone, and that mucus-secreting goblet cell hyperplasia and collagen deposition in the airways were also ameliorated by administration of sauchinone treatment. Moreover, gene expression of the inflammatory cytokines, IL-13, and IL-5 and eotaxin in the lung, and IL-5 in the draining lymph node were significantly decreased in sauchinone-treated mice. We demonstrated that sauchinone repressed Th2 cell development in vitro and IL-4 production by Th2 cells, and also inhibited GATA-3-mediated IL-5 promoter activity in a dose-dependent manner. Collectively, sauchinone ameliorated allergen-induced airway inflammation, in part, by repressing GATA-3 activity for Th2 cell development, indicating the possible therapeutic potential of sauchinone in airway inflammatory diseases including allergic asthma and rhinitis.
    Full-text · Article · Jun 2009 · Biochemical and Biophysical Research Communications
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    • "Recently, there have been many studies concerning natural products with anti-inflammatory activity, for example, Polygonum tinctorium (13), Melia azedarach (14), Cyperus rotundus (15,16), Cudrania tricuspidata (17), Ginsenoside Rg3 (18), sauchinone (19,20), curcuma rhizomes (21) and Farfarae Flos (22). Although Moutan Cortex has been used as an anti-inflammatory agent in oriental medicine, the mechanisms of anti-iflammatory activity of Moutan Cortex have not been studied scientifically. "
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    ABSTRACT: Moutan Cortex (MCE) has been used in traditional medicine to remove heat from the blood, promote blood circulation and alleviate blood stasis. This study was conducted to evaluate the effects of MCE on regulatory mechanisms of cytokines and nitric oxide (NO) involved in immunological activity of Raw264.7 cells. Cells were pretreated with methanolic extracts of MCE, and further cultured for an appropriate time after lipopolyssacharide (LPS) addition. During the entire experimental period, 0.1 and 0.3 mg ml(-1) of MCE had no cytotoxicity. In these concentrations, MCE inhibited the production of NO and prostaglandin E(2) (PGE(2)), the expression of inducible NO synthase (iNOS), cyclooxygenase-2 (COX-2) and phosphorylated inhibitor of kappa Bal pha (p-I kappa Bal pha), and the activation of nuclear factor kappa B (NF-kappa B). MCE also reduced the concentration of tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta) and interleukin-6 (IL-6) in the Raw264.7 cells that were activated by LPS. These results demonstrate that MCE has anti-inflammatory effects through the inhibition of iNOS and COX-2 expression by suppressing the phosphorylation of I-kappa Bal pha and the activation of NF-kappa B.
    Full-text · Article · Oct 2007 · Evidence-based Complementary and Alternative Medicine
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    • "Such a research regime of necessity demands close collaboration between expert pharmacognosists/phytochemists and molecular biologists. It should be noted that an effective first level screening is available to phytochemically orientated laboratories (see Hwang et al., 2003) but more in-depth analysis of inhibition specificity requires dedicated molecular systems (see Takada and Aggarwal, 2003). "
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    ABSTRACT: Nuclear factor kappa B (NF-κB) is a transcription factor involved at the downstream stage of many signalling cascades and plays a crucial role in acute and chronic inflammatory conditions, induced and adaptive immunity, apoptosis and induced cell proliferation. For the last decade it has attracted intense research interest throughout the world. This review briefly expands on information on biogenic modulators of this transcription factor published since an earlier review in 2002 and goes into much more detail on parthenolide and curcumin – two natural products that have been at the centre of molecular and biochemical interest in identifying modulators of the NF-κB pathway. Both compounds have attracted considerable attention in regard to the mechanistic aspects of the compounds’ action. An attempt to further develop some compounds into leads for new medicines are also discussed, focusing on an EU-funded project on anti-inflammatory natural products, mostly from medicinal plants used locally in selected Mediterranean regions.
    Full-text · Article · Dec 2004 · Phytochemistry Reviews
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