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Inflammation Research

, Volume 63, Issue 1, pp 81–90 | Cite as

Anti-inflammatory effects of chlorogenic acid in lipopolysaccharide-stimulated RAW 264.7 cells

  • Su Jung Hwang
  • Yong-Wan Kim
  • Yohan Park
  • Hyo-Jong LeeEmail author
  • Kyu-Won KimEmail author
Original Research Paper

Abstract

Objectives and design

Chlorogenic acid, which belongs to the polyphenols, is an anti-oxidant and anti-obesity agent. In this study, we investigated the role of chlorogenic acid in inflammation.

Materials and methods

Anti-inflammatory effects of chlorogenic acid were examined in lipopolysaccharide (LPS)-stimulated murine RAW 264.7 macrophages and BV2 microglial cells. We observed the level of various inflammation markers such as nitric oxide (NO), inducible NO synthase (iNOS), cyclooxygenase-2 (COX-2), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), and chemokine (C-X-C motif) ligand 1 (CXCL1) under LPS treatment with or without chlorogenic acid. To clarify the specific effect of chlorogenic acid, we evaluated the adhesion activity of macrophages and ninjurin1 (Ninj1) expression level in macrophages. Finally, we confirmed the activation of the nuclear factor-κB (NF-κB) signaling pathway, which is one of the most important transcription factors in the inflammatory process.

Results

Chlorogenic acid significantly inhibited not only NO production but also the expression of COX-2 and iNOS, without any cytotoxicity. Chlorogenic acid also attenuated pro-inflammatory cytokines (including IL-1β and TNF-α) and other inflammation-related markers such as IL-6 in a dose-dependent manner. Additionally, endotoxin-induced adhesion of macrophages and the expression level of ninjurin1 (Ninj1) were decreased by chlorogenic acid. Finally, chlorogenic acid inhibited the nuclear translocation of NF-κB.

Conclusions

Chlorogenic acid may be beneficial for the prevention and treatment of anti-inflammatory diseases.

Keywords

Chlorogenic acid Nitric oxide Cytokines Ninjurin1 Inflammation 

Notes

Acknowledgments

This work was supported by a National Research Foundation of Korea (NRF) grant funded by the Ministry of Education, Science and Technology (MEST) through the Global Research Laboratory Program (2011-0021874), the World Class University Program (R31-2008-000-10103-0), and the Global Core Research Center (GCRC) Program (2012-0001187).

References

  1. 1.
    Ferrero-Miliani L, Nielsen OH, Andersen PS, Girardin SE. Chronic inflammation: importance of NOD2 and NALP3 in interleukin-1beta generation. Clin Exp Immunol. 2007;147:227–35.PubMedCentralPubMedGoogle Scholar
  2. 2.
    Boyce JA. Eicosanoids in asthma, allergic inflammation, and host defense. Curr Mol Med. 2008;8:335–49.PubMedCrossRefGoogle Scholar
  3. 3.
    Lee IT, Yang CM. Inflammatory signalings involved in airway and pulmonary diseases. Mediators Inflamm. 2013;2013:791231. doi: 10.1155/2013/791231.PubMedCentralPubMedGoogle Scholar
  4. 4.
    Barin JG, Rose NR, Cihakova D. Macrophage diversity in cardiac inflammation: a review. Immunobiology. 2011;217:468–75.PubMedCrossRefGoogle Scholar
  5. 5.
    Papageorgiou AP, Heymans S. Interactions between the extracellular matrix and inflammation during viral myocarditis. Immunobiology. 2011;217:503–10.PubMedCrossRefGoogle Scholar
  6. 6.
    Chen YW, Pat B, Gladden JD, Zheng J, Powell P, Wei CC, et al. Dynamic molecular and histopathological changes in the extracellular matrix and inflammation in the transition to heart failure in isolated volume overload. Am J Physiol Heart Circ Physiol. 2011;300:H2251–60.PubMedCrossRefGoogle Scholar
  7. 7.
    Korhonen R, Lahti A, Kankaanranta H, Moilanen E. Nitric oxide production and signaling in inflammation. Curr Drug Targets Inflamm Allergy. 2005;4:471–9.PubMedCrossRefGoogle Scholar
  8. 8.
    Montiel-Duarte C, Ansorena E, Lopez-Zabalza MJ, Cenarruzabeitia E, Iraburu MJ. Role of reactive oxygen species, glutathione and NF-kappaB in apoptosis induced by 3,4-methylenedioxymethamphetamine (“Ecstasy”) on hepatic stellate cells. Biochem Pharmacol. 2004;67:1025–33.PubMedCrossRefGoogle Scholar
  9. 9.
    Francisco V, Costa G, Figueirinha A, Marques C, Pereira P, Miguel Neves B, et al. Anti-inflammatory activity of Cymbopogon citratus leaves infusion via proteasome and nuclear factor-kappaB pathway inhibition: contribution of chlorogenic acid. J Ethnopharmacol. 2013;148:126–34.PubMedCrossRefGoogle Scholar
  10. 10.
    Wu Y, Liu Y, Huang H, Zhu Y, Zhang Y, Lu F, et al. Dexmedetomidine inhibits inflammatory reaction in lung tissues of septic rats by suppressing TLR4/NF-kappa B pathway. Mediators Inflamm. 2013;2013:562154. doi: 10.1155/2013/562154.PubMedCentralPubMedGoogle Scholar
  11. 11.
    Nam NH. Naturally occurring NF-κB inhibitors. Mini Rev Med Chem. 2006;6:945–51.PubMedCrossRefGoogle Scholar
  12. 12.
    Li X, Li Z, Zheng Z, Liu Y, Ma X. Unfractionated heparin ameliorates lipopolysaccharide-induced lung inflammation by downregulating nuclear factor-kappaB signaling pathway. Inflammation. 2013; doi:  10.1007/s10753-013-9656-5.
  13. 13.
    Gonthier MP, Verny MA, Besson C, Remesy C, Scalbert A. Chlorogenic acid bioavailability largely depends on its metabolism by the gut microflora in rats. J Nutr. 2003;133:1853–9.PubMedGoogle Scholar
  14. 14.
    Hulme AC. The isolation of chlorogenic acid from the apple fruit. Biochem J. 1953;53:337–40.PubMedGoogle Scholar
  15. 15.
    Zang LY, Cosma G, Gardner H, Castranova V, Vallyathan V. Effect of chlorogenic acid on hydroxyl radical. Mol Cell Biochem. 2003;247:205–10.PubMedCrossRefGoogle Scholar
  16. 16.
    Ong KW, Hsu A, Tan BK. Anti-diabetic and anti-lipidemic effects of chlorogenic acid are mediated by AMPK activation. Biochem Pharmacol. 2013;85:1341–51.PubMedCrossRefGoogle Scholar
  17. 17.
    Suzuki A, Yamamoto N, Jokura H, Yamamoto M, Fujii A, Tokimitsu I, et al. Chlorogenic acid attenuates hypertension and improves endothelial function in spontaneously hypertensive rats. J Hypertens. 2006;24:1065–73.PubMedCrossRefGoogle Scholar
  18. 18.
    Jung HA, Park JC, Chung HY, Kim J, Choi JS. Antioxidant flavonoids and chlorogenic acid from the leaves of Eriobotrya japonica. Arch Pharm Res. 1999;22:213–8.PubMedCrossRefGoogle Scholar
  19. 19.
    Han HE, Kim TK, Son HJ, Park W, Han PL. Activation of autophagy pathway suppresses the expression of iNOS, IL6 and cell death of LPS-stimulated microglia cells. Biomol Ther. 2013;21:21–8.CrossRefGoogle Scholar
  20. 20.
    Kang TJ, Moon JS, Lee SY, Yim DS. Polyacetylene compound from Cirsium japonicum var. ussuriense inhibits the LPS-induced inflammatory reaction via suppression of NF-κB activity in Raw 264.7 cells. Biomol Ther 2011; 19:97–101.Google Scholar
  21. 21.
    Lee HJ, Ahn BJ, Shin MW, Choi JH, Kim KW. Ninjurin1: a potential adhesion molecule and its role in inflammation and tissue remodeling. Mol Cells. 2010;29:223–7.PubMedCrossRefGoogle Scholar
  22. 22.
    Shi H, Dong L, Jiang J, Zhao J, Zhao G, Dang X, et al. Chlorogenic acid reduces liver inflammation and fibrosis through inhibition of toll-like receptor 4 signaling pathway. Toxicology. 2013;303:107–14.PubMedCrossRefGoogle Scholar
  23. 23.
    Lee SA, Jung EB, Lee SH, Kim YJ, Bang H, Seo SJ, et al. 3,4,5-Tricaffeoylquinic acid inhibits the lipopolysaccharide-stimulated production of inflammatory mediators in keratinocytes. Pharmacology. 2012;90:183–92.PubMedCrossRefGoogle Scholar
  24. 24.
    Sachithanandan N, Graham KL, Galic S, Honeyman JE, Fynch SL, Hewitt KA, et al. Macrophage deletion of SOCS1 increases sensitivity to LPS and palmitic acid and results in systemic inflammation and hepatic insulin resistance. Diabetes. 2011;60:2023–31.PubMedCrossRefGoogle Scholar
  25. 25.
    Lee H, Bae S, Choi BW, Yoon Y. WNT/beta-catenin pathway is modulated in asthma patients and LPS-stimulated RAW264.7 macrophage cell line. Immunopharmacol Immunotoxicol. 2011;34:56–65.PubMedCrossRefGoogle Scholar
  26. 26.
    Karpurapu M, Wang X, Deng J, Park H, Xiao L, Sadikot RT, et al. Functional PU.1 in macrophages has a pivotal role in NF-{kappa}B activation and neutrophilic lung inflammation during endotoxemia. Blood. 2011;118:5255–66.PubMedCrossRefGoogle Scholar
  27. 27.
    Lee HJ, Kim KW. Anti-inflammatory effects of arbutin in lipopolysaccharide-stimulated BV2 microglial cells. Inflamm Res. 2012;61:817–25.PubMedCrossRefGoogle Scholar
  28. 28.
    Ahn BJ, Lee HJ, Shin MW, Choi JH, Jeong JW, Kim KW. Ninjurin1 is expressed in myeloid cells and mediates endothelium adhesion in the brains of EAE rats. Biochem Biophys Res Commun. 2009;387:321–5.PubMedCrossRefGoogle Scholar
  29. 29.
    Lee HJ, Ahn BJ, Shin MW, Jeong JW, Kim JH, Kim KW. Ninjurin1 mediates macrophage-induced programmed cell death during early ocular development. Cell Death Differ. 2009;16:1395–407.PubMedCrossRefGoogle Scholar
  30. 30.
    Tucsek Z, Radnai B, Racz B, Debreceni B, Priber JK, Dolowschiak T, et al. Suppressing LPS-induced early signal transduction in macrophages by a polyphenol degradation product: a critical role of MKP-1. J Leukoc Biol. 2011;89:105–11.PubMedCrossRefGoogle Scholar
  31. 31.
    Baowen Q, Yulin Z, Xin W, Wenjing X, Hao Z, Zhizhi C, et al. A further investigation concerning correlation between anti-fibrotic effect of liposomal quercetin and inflammatory cytokines in pulmonary fibrosis. Eur J Pharmacol. 2010;642:134–9.PubMedCrossRefGoogle Scholar
  32. 32.
    van Dijk AE, Olthof MR, Meeuse JC, Seebus E, Heine RJ, van Dam RM. Acute effects of decaffeinated coffee and the major coffee components chlorogenic acid and trigonelline on glucose tolerance. Diabetes Care. 2009;32:1023–5.PubMedCrossRefGoogle Scholar
  33. 33.
    Prabhakar PK, Doble M. Synergistic effect of phytochemicals in combination with hypoglycemic drugs on glucose uptake in myotubes. Phytomedicine. 2009;16:1119–26.PubMedCrossRefGoogle Scholar
  34. 34.
    Ong KW, Hsu A, Tan BK. Chlorogenic acid stimulates glucose transport in skeletal muscle via AMPK activation: a contributor to the beneficial effects of coffee on diabetes. PLoS One. 2012;7:e32718.PubMedCentralPubMedCrossRefGoogle Scholar

Copyright information

© Springer Basel 2013

Authors and Affiliations

  1. 1.College of PharmacyInje UniversityGimhaeRepublic of Korea
  2. 2.SNU-Harvard NeuroVascular Protection Research Center, College of Pharmacy and Research Institute of Pharmaceutical SciencesSeoul National UniversitySeoulRepublic of Korea
  3. 3.Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and TechnologySeoul National UniversitySeoulRepublic of Korea

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