Skip to main content
SpringerLink
Log in

Licochalcone A isolated from licorice suppresses lipopolysaccharide-stimulated inflammatory reactions in RAW264.7 cells and endotoxin shock in mice

  • Original Article
  • Published:
Journal of Molecular Medicine Aims and scope Submit manuscript

Abstract

Licochalcone A (LicA), a major phenolic constituent of the licorice species Glycyrrhiza inflata, exhibits various biological properties, including chemopreventive, anti-bacterial, and anti-spasmodic activity. We report that LicA inhibits inflammatory reactions in macrophages and protects mice from endotoxin shock. Our in vitro experiments showed that LicA suppressed not only the generation of nitric oxide (NO) and prostaglandin (PG)E2, but also the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2 induced by lipopolysaccharide (LPS) in RAW264.7 cells. Similarly, LicA inhibited the production of inflammatory cytokines induced by LPS in RAW264.7 cells, including IL-1β and IL-6. In an animal model, LicA protected BALB/c mice from LPS-induced endotoxin shock, possibly through inhibiting the production of inflammatory cytokines and NO. Collectively, LicA inhibited the production of inflammatory mediators and may be a potential target for treatment of various inflammatory diseases.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

References

  1. O’Shea JJ, Murray PJ (2008) Cytokine signaling modules in inflammatory responses. Immunity 28:477–487

    Article  PubMed  CAS  Google Scholar 

  2. Lawrence TD, Willoughby A, Gilroy DW (2002) Anti-inflammatory lipid mediators and insights into the resolution of inflammation. Nat Rev Immunol 2:787–795

    Article  PubMed  CAS  Google Scholar 

  3. Blackwell TS, Christman JW (1997) The role of nuclear factor-kappa B in cytokine gene regulation. Am J Respir Cell Mol Biol 7:3–9

    Google Scholar 

  4. Lang RM, Hammer M, Mages J (2006) DUSP meet immunology: dual specificity MAPK phosphatases in control of the inflammatory response. J Immunol 177:7497–7504

    PubMed  CAS  Google Scholar 

  5. Wang J, Gigliotti F, Bhagwat SP, Maggirwar SB, Wright TW (2007) Pneumocystis stimulates MCP-1 production by alveolar epithelial cells through a JNK-dependent mechanism. Am J Physiol Lung Cell Mol Physiol 292:L1495–L1505

    Article  PubMed  CAS  Google Scholar 

  6. Park JS, Lee EJ, Lee JC, Kim WK, Kim HS (2007) Anti-inflammatory effects of short chain fatty acids in IFN-gamma-stimulated RAW264.7 murine macrophage cells: involvement of NF-kappaB and ERK signaling pathways. Int Immunopharmacol 7:70–77

    Article  PubMed  CAS  Google Scholar 

  7. Ajizian SJ, English BK, Meals EA (1999) Specific inhibitors of p38 and extracellular signal-regulated kinase mitogen-activated protein kinase pathways block inducible nitric oxide synthase and tumor necrosis factor accumulation in murine macrophages stimulated with lipopolysaccharide and interferon-gamma. J Infect Dis 179:939–944

    Article  PubMed  CAS  Google Scholar 

  8. Chan ED, Riches DW (1998) Potential role of the JNK/SAPK signal transduction pathway in the induction of iNOS by TNF-alpha. Biochem Biophys Res Commun 253:790–796

    Article  PubMed  CAS  Google Scholar 

  9. Carter AB, Monick MM, Hunninghake GW (1999) Both Erk and p38 kinases are necessary for cytokine gene transcription. Am J Respir Cell Mol Biol 20:751–758

    PubMed  CAS  Google Scholar 

  10. Tominaga K, Saito S, Matsuura M, Nakano M (1999) Lipopolysaccharide tolerance in murine peritoneal macrophages induces downregulation of the lipopolysaccharide signal transduction pathway through mitogen-activated protein kinase and nuclear factor-kappaB cascades, but not lipopolysaccharide-incorporation steps. Biochim Biophys Acta 1450:130–144

    Article  PubMed  CAS  Google Scholar 

  11. Fukai T, Marumo A, Kaitou K, Kanda T, Terada S, Nomura T (2002) Anti-Helicobacter pylori flavonoids from licorice extract. Life Sci 71:1449–1463

    Article  PubMed  CAS  Google Scholar 

  12. Nielsen SF, Boesen T, Larsen M, Schonning K, Kromann H (2004) Antibacterial chalcones—bioisosteric replacement of the 4′-hydroxy group. Bioorg Med Chem 12:3047–3054

    Article  PubMed  CAS  Google Scholar 

  13. Ziegler HL, Hansen HS, Staerk D, Christensen SB, Hagerstrand H, Jaroszewski JW (2004) The antiparasitic compound licochalcone a is a potent echinocytogenic agent that modifies the erythrocyte membrane in the concentration range where antiplasmodial activity is observed. Antimicrob Agents Chemother 48:4067–4071

    Article  PubMed  CAS  Google Scholar 

  14. Fu YT, Hsieh C, Guo J, Kunicki J, Lee MY, Darzynkiewicz Z, Wu JM (2004) Licochalcone-A, a novel flavonoid isolated from licorice root (Glycyrrhiza glabra), causes G2 and late-G1 arrests in androgen-independent PC-3 prostate cancer cells. Biochem Biophys Res Commun 322:263–270

    Article  PubMed  CAS  Google Scholar 

  15. Barfod L, Kemp K, Hansen M, Kharazmi A (2002) Chalcones from Chinese liquorice inhibit proliferation of T cells and production of cytokines. Int Immunopharmacol 2:545–555

    Article  PubMed  CAS  Google Scholar 

  16. Guha M, Mackman N (2001) LPS induction of gene expression in human monocytes. Cell Signal 13:85–94

    Article  PubMed  CAS  Google Scholar 

  17. Ohsawa M, Koyama T, Nara N, Hirosawa S (2003) Induction of tissue factor expression in human monocytic cells by protease inhibitors through activating activator protein-1 (AP-1) with phosphorylation of Jun-N-terminal kinase and p38. Thromb Res 112:313–320

    Article  PubMed  CAS  Google Scholar 

  18. Fukai T, Satoh K, Nomura T, Sakagami H (2003) Preliminary evaluation of antinephritis and radical scavenging activities of glabridin from Glycyrrhiza inflate. Fitoterapia 74:624–629

    Article  PubMed  CAS  Google Scholar 

  19. Kwon HS, Oh SM, Kim JK (2008) Glabridin, a functional compound of liquorice, attenuates colonic inflammation in mice with dextran sulphate sodium-induced colitis. Clin Exp Immunol 151:165–173

    Article  PubMed  CAS  Google Scholar 

  20. Carbonell-Barrachina AA, Aracil P, Garcia E, Burlo F, Martinez-Sanchez F (2003) Source of arsenic in licorice confectionery products. J Agric Food Chem 51:1749–1752

    Article  PubMed  CAS  Google Scholar 

  21. Kim JK, Oh SM, Kwon HS, Oh YS, Lim SS, Shin HK (2006) Anti-inflammatory effect of roasted licorice extracts on lipopolysaccharide-induced inflammatory responses in murine macrophages. Biochem Biophys Res Commun 345:1215–1223

    Article  PubMed  CAS  Google Scholar 

  22. Kamimura D, Ishihara K, Hirano T (2003) IL-6 signal transduction and its physiological roles: the signal orchestration model. Rev Physiol Biochem Pharmacol 149:1–38

    Article  PubMed  CAS  Google Scholar 

  23. Aktan F (2004) iNOS-mediated nitric oxide production and its regulation. Life Sci 75:639–653

    Article  PubMed  CAS  Google Scholar 

  24. Cho MK, Suh SH, Kim SG (2002) JunB/AP-1 and NF-kappa B-mediated induction of nitric oxide synthase by bovine type I collagen in serum-stimulated murine macrophages. Nitric Oxide 6:319–332

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This work was supported by the Korea Science and Engineering Foundation (KOSEF) grant funded by the Korean government (MOST; R01-2007-000-20164) and Regional Innovation Center (RIC) program of the Ministry of Commerce, Industry, and Energy, Republic of Korea.

Author information

Authors and Affiliations

  1. Center for Efficacy Assessment and Development of Functional Foods and Drugs, Hallym University, Hallymdaehak-gil 39, Chuncheon, 200-702, Republic of Korea

    Hyuck-Se Kwon, Jun Hong Park, Dae Hwan Kim, Yoon Hee Kim, Hyun-Kyung Shin & Jin-Kyung Kim

  2. Department of Food Science and Nutrition, Hallym University, Chuncheon, Republic of Korea

    Jung Han Yoon Park & Hyun-Kyung Shin

Authors
  1. Hyuck-Se Kwon
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jun Hong Park
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Dae Hwan Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yoon Hee Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jung Han Yoon Park
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Hyun-Kyung Shin
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Jin-Kyung Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jin-Kyung Kim.

Additional information

Hyuck-Se Kwon, Jun Hong Park, and Dae Hwan Kim have contributed equally to this work.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary Fig. 1

Blots of the indicated figures for reactivity of antibodies used in our manuscript. For experimental method, see legends of the indicated figure and “Materials and methods” section (JPG 28 kb)

High resolution image file (TIF 92 KB)

Supplementary Fig. 2

Blots of the indicated figures for reactivity of antibodies used in our manuscript. For experimental method, see legends of the indicated figure and “Materials and methods” section (JPG 42 kb)

Supplementary Fig. 3

Blots of the indicated figures for reactivity of antibodies used in our manuscript. For experimental method, see legends of the indicated figure and “Materials and methods” section (JPG 27 kb)

Supplementary Fig. 4

Blots of the indicated figures for reactivity of antibodies used in our manuscript. For experimental method, see legends of the indicated figure and “Materials and methods” section (JPG 28 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kwon, HS., Park, J.H., Kim, D.H. et al. Licochalcone A isolated from licorice suppresses lipopolysaccharide-stimulated inflammatory reactions in RAW264.7 cells and endotoxin shock in mice. J Mol Med 86, 1287–1295 (2008). https://doi.org/10.1007/s00109-008-0395-2

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00109-008-0395-2

Keywords

Search

Navigation