Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
Molecular Medicine Reports
Join Editorial Board Propose a Special Issue
Print ISSN: 1791-2997 Online ISSN: 1791-3004
Journal Cover
December-2014 Volume 10 Issue 6

Full Size Image

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
December-2014 Volume 10 Issue 6

Full Size Image

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML
Article

Esculetin suppresses lipopolysaccharide-induced inflammatory mediators and cytokines by inhibiting nuclear factor-κB translocation in RAW 264.7 macrophages

  • Authors:
    • Su Hyun Hong
    • Hui-Kyung Jeong
    • Min Ho Han
    • Cheol Park
    • Yung Hyun Choi
  • View Affiliations / Copyright

    Affiliations: Department of Biochemistry, Dongeui University College of Oriental Medicine, Busan 614-052, Republic of Korea, Department of Molecular Biology, College of Natural Sciences, Dongeui University, Busan 614-714, Republic of Korea
  • Pages: 3241-3246
    |
    Published online on: October 8, 2014
       https://doi.org/10.3892/mmr.2014.2613
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



Abstract

Although previous studies have demonstrated that the natural coumarin compound esculetin possesses various pharmacological properties, the molecular mechanism of esculetin-mediated anti-inflammatory potential is not fully understood. In this study, we determined the effects of esculetin on lipopolysaccharide (LPS)-induced inflammatory responses of murine RAW 264.7 macrophages. The results indicate that esculetin inhibits LPS-induced nitric oxide and prostaglandin E2 production in a concentration-dependent manner, and inhibits inducible nitric oxide synthase and cyclooxygenase-2 expression in RAW 264.7 cells. Esculetin also significantly suppresses the production of inflammatory cytokines, including tumor necrosis factor-α and interleukin-1β, which was concomitant with a decrease in their expression levels. Furthermore, it was observed that esculetin attenuated the LPS-mediated nuclear factor-kappa B (NF-κB) translocation associated with the blocking of inhibitor of NF-κB (IκB)-α degradation as well as reactive oxygen species (ROS) production, without any significant cytotoxicity. These data suggest that, by blocking NF-κB activation, esculetin suppresses LPS-elicited inflammatory events, and this is mediated, at least in part, by inhibiting the generation of ROS. Collectively, these findings provide mechanistic insights into the anti-inflammatory action of esculetin in macrophages.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

View References

1 

Vendramini-Costa DB and Carvalho JE: Molecular link mechanisms between inflammation and cancer. Curr Pharm Des. 18:3831–3852. 2012. View Article : Google Scholar : PubMed/NCBI

2 

Ma A, Qi S and Chen H: Antioxidant therapy for prevention of inflammation, ischemic reperfusion injuries and allograft rejection. Cardiovasc Hematol Agents Med Chem. 6:20–43. 2008. View Article : Google Scholar : PubMed/NCBI

3 

Carreira PE: Pulmonary hypertension in autoimmune rheumatic diseases. Autoimmun Rev. 313–320. 2004. View Article : Google Scholar

4 

Fialkow L, Wang Y and Downey GP: Reactive oxygen and nitrogen species as signaling molecules regulating neutrophil function. Free Radic Biol Med. 42:153–164. 2007. View Article : Google Scholar : PubMed/NCBI

5 

Geronikaki AA and Gavalas AM: Antioxidants and inflammatory disease: synthetic and natural antioxidants with anti-inflammatory activity. Comb Chem High Throughput Screen. 9:425–442. 2006. View Article : Google Scholar : PubMed/NCBI

6 

Gasparini C and Feldmann M: NF-κB as a target for modulating inflammatory responses. Curr Pharm Des. 18:5735–5745. 2012.

7 

Lawrence T: The nuclear factor NF-kappaB pathway in inflammation. Cold Spring Harb Perspect Biol. 1:a0016512009. View Article : Google Scholar : PubMed/NCBI

8 

Siomek A: NF-κB signaling pathway and free radical impact. Acta Biochim Pol. 59:323–331. 2012.

9 

Temkin V and Karin M: From death receptor to reactive oxygen species and c-Jun N-terminal protein kinase: the receptor-interacting protein 1 odyssey. Immunol Rev. 220:8–21. 2007. View Article : Google Scholar : PubMed/NCBI

10 

Morgan MJ and Liu ZG: Crosstalk of reactive oxygen species and NF-κB signaling. Cell Res. 21:103–115. 2011.

11 

Gloire G, Legrand-Poels S and Piette J: NF-kappaB activation by reactive oxygen species: fifteen years later. Biochem Pharmacol. 72:1493–1505. 2006.PubMed/NCBI

12 

Fylaktakidou KC, Hadjipavlou-Litina DJ, Litinas KE and Nicolaides DN: Natural and synthetic coumarin derivatives with anti-inflammatory/antioxidant activities. Curr Pharm Des. 10:3813–3833. 2004. View Article : Google Scholar : PubMed/NCBI

13 

Witaicenis A, Seito LN and Di Stasi LC: Intestinal anti-inflammatory activity of esculetin and 4-methylesculetin in the trinitrobenzenesulphonic acid model of rat colitis. Chem Biol Interact. 186:211–218. 2010. View Article : Google Scholar : PubMed/NCBI

14 

Kwon OS, Choi JS, Islam MN, Kim YS and Kim HP: Inhibition of 5-lipoxygenase and skin inflammation by the aerial parts of Artemisia capillaris and its constituents. Arch Pharm Res. 34:1561–1569. 2011. View Article : Google Scholar : PubMed/NCBI

15 

Prabakaran D and Ashokkumar N: Protective effect of esculetin on hyperglycemia-mediated oxidative damage in the hepatic and renal tissues of experimental diabetic rats. Biochimie. 95:366–373. 2013. View Article : Google Scholar : PubMed/NCBI

16 

Subramaniam SR and Ellis EM: Esculetin-induced protection of human hepatoma HepG2 cells against hydrogen peroxide is associated with the Nrf2-dependent induction of the NAD(P)H: Quinone oxidoreductase 1 gene. Toxicol Appl Pharmacol. 250:130–136. 2011. View Article : Google Scholar

17 

Kim SH, Kang KA, Zhang R, et al: Protective effect of esculetin against oxidative stress-induced cell damage via scavenging reactive oxygen species. Acta Pharmacol Sin. 29:1319–1326. 2008. View Article : Google Scholar : PubMed/NCBI

18 

Lee CR, Shin EJ, Kim HC, et al: Esculetin inhibits N-methyl-D-aspartate neurotoxicity via glutathione preservation in primary cortical cultures. Lab Anim Res. 27:259–263. 2011. View Article : Google Scholar : PubMed/NCBI

19 

Leung KN, Leung PY, Kong LP and Leung PK: Immunomodulatory effects of esculetin (6,7-dihydroxycoumarin) on murine lymphocytes and peritoneal macrophages. Cell Mol Immunol. 2:181–188. 2005.PubMed/NCBI

20 

Park C, Jin CY, Kim GY, et al: Induction of apoptosis by esculetin in human leukemia U937 cells through activation of JNK and ERK. Toxicol Appl Pharmacol. 227:219–228. 2008. View Article : Google Scholar : PubMed/NCBI

21 

Park C, Jin CY, Kwon HJ, et al: Induction of apoptosis by esculetin in human leukemia U937 cells: roles of Bcl-2 and extracellular-regulated kinase signaling. Toxicol In Vitro. 24:486–494. 2010. View Article : Google Scholar : PubMed/NCBI

22 

Kyung J, Kim D, Park D, et al: Synergistic anti-inflammatory effects of Laminaria japonica fucoidan and Cistanche tubulosa extract. Lab Anim Res. 28:91–97. 2012. View Article : Google Scholar

23 

Lee SH, Kim DW, Eom SA, et al: Suppression of 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced skin inflammation in mice by transduced Tat-Annexin protein. BMB Rep. 45:354–359. 2012. View Article : Google Scholar : PubMed/NCBI

24 

Sekiya K, Okuda H and Arichi S: Selective inhibition of platelet lipoxygenase by esculetin. Biochim Biophys Acta. 713:68–72. 1982. View Article : Google Scholar : PubMed/NCBI

25 

Yang CS, Yuk JM and Jo EK: The role of nitric oxide in mycobacterial infections. Immune Netw. 9:46–52. 2009. View Article : Google Scholar : PubMed/NCBI

26 

Rimoldi JM and Chimote SS: Inhibition on inducible nitric oxide synthase. Curr Opin Drug Discov Devel. 1:183–191. 1998.PubMed/NCBI

27 

Murakami A and Ohigashi H: Targeting NOX, INOS and COX-2 in inflammatory cells: chemoprevention using food phytochemicals. Int J Cancer. 121:2357–2363. 2007. View Article : Google Scholar : PubMed/NCBI

28 

Wadleigh DJ, Reddy ST, Kopp E, Ghosh S and Herschman HR: Transcriptional activation of the cyclooxygenase-2 gene in endotoxin-treated RAW 264.7 macrophages. J Biol Chem. 275:6259–6266. 2000. View Article : Google Scholar : PubMed/NCBI

29 

Kanno S, Shouji A, Tomizawa A, et al: Inhibitory effect of naringin on lipopolysaccharide (LPS)-induced endotoxin shock in mice and nitric oxide production in RAW 264.7 macrophages. Life Sci. 78:673–681. 2006. View Article : Google Scholar : PubMed/NCBI

30 

Lin WJ and Yeh WC: Implication of Toll-like receptor and tumor necrosis factor alpha signaling in septic shock. Shock. 24:206–209. 2005. View Article : Google Scholar : PubMed/NCBI

31 

Dayer JM: The process of identifying and understanding cytokines: from basic studies to treating rheumatic diseases. Best Pract Res Clin Rheumatol. 18:31–45. 2004. View Article : Google Scholar : PubMed/NCBI

32 

Guha M and Mackman N: LPS induction of gene expression in human monocytes. Cell Signal. 13:85–94. 2001. View Article : Google Scholar

33 

Pearlman DS: Pathophysiology of the inflammatory response. J Allergy Clin Immunol. 104:S132–S137. 1999. View Article : Google Scholar : PubMed/NCBI

34 

Beutler B and Cerami A: The biology of cachectin/TNF-α primary mediator of the host response. Annu Rev Immunol. 7:625–655. 1989.

35 

Blatteis CM, Li S, Li Z, Perlik V and Feleder C: Signaling the brain in systemic inflammation: the role of complement. Front Biosci. 9:915–931. 2004. View Article : Google Scholar : PubMed/NCBI

36 

Aggarwal BB and Natarajan K: Tumor necrosis factors: developments during the last decade. Eur Cytokine Netw. 7:93–124. 1996.PubMed/NCBI

37 

Moynagh PN: The NF-kappaB pathway. J Cell Sci. 118:4589–4592. 2005. View Article : Google Scholar : PubMed/NCBI

38 

Sarkar FH, Li Y, Wang Z and Kong D: NF-kappaB signaling pathway and its therapeutic implications in human diseases. Int Rev Immunol. 27:293–319. 2008. View Article : Google Scholar : PubMed/NCBI

39 

Makarov SS: NF-kappaB as a therapeutic target in chronic inflammation: recent advances. Mol Med Today. 6:441–448. 2000. View Article : Google Scholar : PubMed/NCBI

40 

Islam MN, Choi RJ, Jin SE, et al: Mechanism of anti-inflammatory activity of umbelliferone 6-carboxylic acid isolated from Angelica decursiva. J Ethnopharmacol. 144:175–181. 2012. View Article : Google Scholar : PubMed/NCBI

41 

Jung WK, Choi I, Lee DY, et al: Caffeic acid phenethyl ester protects mice from lethal endotoxin shock and inhibits lipopolysaccharide-induced cyclooxygenase-2 and inducible nitric oxide synthase expression in RAW 264.7 macrophages via the p38/ERK and NF-kappaB pathways. Int J Biochem Cell Biol. 40:2572–2582. 2008. View Article : Google Scholar

42 

Harris J, Olière S, Sharma S, et al: Nuclear accumulation of cRel following C-terminal phosphorylation by TBK1/IKK epsilon. J Immunol. 177:2527–2535. 2006. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Hong SH, Jeong H, Han MH, Park C and Choi YH: Esculetin suppresses lipopolysaccharide-induced inflammatory mediators and cytokines by inhibiting nuclear factor-κB translocation in RAW 264.7 macrophages. Mol Med Rep 10: 3241-3246, 2014.
APA
Hong, S.H., Jeong, H., Han, M.H., Park, C., & Choi, Y.H. (2014). Esculetin suppresses lipopolysaccharide-induced inflammatory mediators and cytokines by inhibiting nuclear factor-κB translocation in RAW 264.7 macrophages. Molecular Medicine Reports, 10, 3241-3246. https://doi.org/10.3892/mmr.2014.2613
MLA
Hong, S. H., Jeong, H., Han, M. H., Park, C., Choi, Y. H."Esculetin suppresses lipopolysaccharide-induced inflammatory mediators and cytokines by inhibiting nuclear factor-κB translocation in RAW 264.7 macrophages". Molecular Medicine Reports 10.6 (2014): 3241-3246.
Chicago
Hong, S. H., Jeong, H., Han, M. H., Park, C., Choi, Y. H."Esculetin suppresses lipopolysaccharide-induced inflammatory mediators and cytokines by inhibiting nuclear factor-κB translocation in RAW 264.7 macrophages". Molecular Medicine Reports 10, no. 6 (2014): 3241-3246. https://doi.org/10.3892/mmr.2014.2613
Copy and paste a formatted citation
x
Spandidos Publications style
Hong SH, Jeong H, Han MH, Park C and Choi YH: Esculetin suppresses lipopolysaccharide-induced inflammatory mediators and cytokines by inhibiting nuclear factor-κB translocation in RAW 264.7 macrophages. Mol Med Rep 10: 3241-3246, 2014.
APA
Hong, S.H., Jeong, H., Han, M.H., Park, C., & Choi, Y.H. (2014). Esculetin suppresses lipopolysaccharide-induced inflammatory mediators and cytokines by inhibiting nuclear factor-κB translocation in RAW 264.7 macrophages. Molecular Medicine Reports, 10, 3241-3246. https://doi.org/10.3892/mmr.2014.2613
MLA
Hong, S. H., Jeong, H., Han, M. H., Park, C., Choi, Y. H."Esculetin suppresses lipopolysaccharide-induced inflammatory mediators and cytokines by inhibiting nuclear factor-κB translocation in RAW 264.7 macrophages". Molecular Medicine Reports 10.6 (2014): 3241-3246.
Chicago
Hong, S. H., Jeong, H., Han, M. H., Park, C., Choi, Y. H."Esculetin suppresses lipopolysaccharide-induced inflammatory mediators and cytokines by inhibiting nuclear factor-κB translocation in RAW 264.7 macrophages". Molecular Medicine Reports 10, no. 6 (2014): 3241-3246. https://doi.org/10.3892/mmr.2014.2613
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team