Anti-inflammatory effects of liquiritigenin as a consequence of the inhibition of NF-κB-dependent iNOS and proinflammatory cytokines production

Authors

  • Y W Kim,

    1. Innovative Drug Research Center for Metabolic and Inflammatory Disease, College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, Korea
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  • R J Zhao,

    1. Department of Pharmacology, Mudanjiang Medical University, Heilongjiang, China
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  • S J Park,

    1. College of Oriental Medicine, Daegu Haany University, Daegu, Korea
    2. BK21 Team, Daegu Haany University, Daegu, Korea
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  • J R Lee,

    1. College of Oriental Medicine, Daegu Haany University, Daegu, Korea
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  • I J Cho,

    1. Innovative Drug Research Center for Metabolic and Inflammatory Disease, College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, Korea
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  • C H Yang,

    1. College of Oriental Medicine, Daegu Haany University, Daegu, Korea
    2. BK21 Team, Daegu Haany University, Daegu, Korea
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  • S G Kim,

    Corresponding author
    1. Innovative Drug Research Center for Metabolic and Inflammatory Disease, College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, Korea
      College of Pharmacy, Seoul National University, Seoul 151-742, Korea. E-mail: sgk@snu.sc.kr
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  • S C Kim

    Corresponding author
    1. College of Oriental Medicine, Daegu Haany University, Daegu, Korea
    2. BK21 Team, Daegu Haany University, Daegu, Korea
      College of Oriental Medicine, Daegu Haany University, Daegu, Korea. E-mail: sckim@dhu.ac.kr
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College of Pharmacy, Seoul National University, Seoul 151-742, Korea. E-mail: sgk@snu.sc.kr

College of Oriental Medicine, Daegu Haany University, Daegu, Korea. E-mail: sckim@dhu.ac.kr

Abstract

Background and purpose:Glycyrrhizae radix has been widely used as a cytoprotective, plant-derived medicine. We have identified a flavanoid, liquiritigenin, as an active component in extracts of Glycyrrhizae radix. This research investigated the effects of liquiritigenin on the induction of inducible NOS (iNOS) and proinflammatory cytokines by lipopolysaccharide (LPS) in Raw264.7 cells, and on paw oedema in rats.

Experimental approach: iNOS expression was determined by western blotting, real-time reverse transcription-PCR and reporter gene analyses. Tumour necrosis factor-α (TNF-α), interleukin (IL)-1β and IL-6 were assayed by ELISA. Gel shift assay and immunoblotting were used to assess NF-κB activation. The effect of liquiritigenin on acute inflammation in vivo was evaluated using carrageenan-induced paw oedema.

Key results: Treatment of Raw264.7 cells with liquiritigenin caused inhibition of LPS-induced NF-κB DNA binding activity, due to repression of I-κBα phosphorylation and degradation. Liquiritigenin treatment prevented LPS from increasing the levels of iNOS protein and mRNA in a concentration-dependent manner. Liquiritigenin also suppressed the production of TNF-α, IL-1β and IL-6 from Raw264.7 cells after LPS. In rats, liquiritigenin treatment inhibited formation of paw oedema induced by carrageenan.

Conclusion and implications: These results demonstrate that liquiritigenin exerts anti-inflammatory effects, which results from the inhibition of NF-κB activation in macrophages, thereby decreasing production of iNOS and proinflammatory cytokines. Our findings showing inhibition by liquiritigenin of paw oedema as well as inflammatory gene induction will help to understand the pharmacology and mode of action of liquiritigenin, and of the anti-inflammatory use of Glycyrrhizae radix.

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