pp 1–9 | Cite as

Curcumin inhibits the expression of proinflammatory mediators and MMP-9 in gingival epithelial cells stimulated for a prolonged period with lipopolysaccharides derived from Porphyromonas gingivalis

  • Seiko Toraya
  • Osamu Uehara
  • Daichi Hiraki
  • Fumiya Harada
  • Puja Neopane
  • Tetsuro Morikawa
  • Rie Takai
  • Koki Yoshida
  • Hirofumi Matsuoka
  • Nobuyoshi Kitaichi
  • Itsuo Chiba
  • Yoshihiro AbikoEmail author
Original Article


Curcumin, a yellow phytochemical found in the rhizomes of Curcuma longa, has various biological effects, including anti-oxidant and anti-inflammatory activities. In the present study, we examined the effect of curcumin on the expression of inflammatory cytokines in human gingival epithelial progenitor cells (HGEPs) stimulated for a prolonged period with lipopolysaccharide (LPS) derived from Porphyromonas gingivalis. The cells were alternately cultured with LPS and/or curcumin every 3 days for 18 days. The expression levels of TNF-α, IL-1β, IL-6, TIMP-1, and MMP-9 in the HGEPs were evaluated by quantitative real-time polymerase chain reaction. Enzyme-linked immunosorbent assay was used to measure the concentrations of these five proteins in the supernatant and nuclear factor (NF)-κB in the nuclear extracts. Curcumin inhibited the mRNA expression levels of TNF-α, IL-, IL-6, and MMP-9 in HGEPs treated with curcumin over a prolonged period. Similarly, the expression levels of IL-1β, IL-6, and MMP-9 were decreased in the culture supernatants. NF-κB activity was also inhibited in the cells cultured with curcumin. In conclusion, these findings indicate that curcumin inhibits the expression of inflammatory cytokines and MMP-9 in primary gingival epithelial cells stimulated with P. gingivalis-derived LPS via NF-κB activation.


P. gingivalis Lipopolysaccharide Curcumin MMP-9 Gingival epithelial cells 



This study was supported in part by a Grant-in-Aid for the 2017–2018 Research Project of the Research Institute of Personalized Health Sciences, Health Sciences University of Hokkaido.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.


  1. 1.
    Huang TS, Lee SC, Lin JK. Suppression of c-Jun/AP-1 activation by an inhibitor of tumor promotion in mouse fibroblast cells. Proc Natl Acad Sci USA. 1991;88:5292–6.CrossRefPubMedGoogle Scholar
  2. 2.
    Singh S, Aggarwal BB. Activation of transcription factor NF-kappa B is suppressed by curcumin (diferuloylmethane). J Biol Chem. 1995;270:24995–5000.CrossRefPubMedGoogle Scholar
  3. 3.
    Abe Y, Hashimoto S, Horie T. Curcumin inhibition of inflammatory cytokine production by human peripheral blood monocytes and alveolar macrophages. Pharmacol Res. 1999;39:41–7.CrossRefPubMedGoogle Scholar
  4. 4.
    Aggarwal BB, Shishodia S, Takada Y, Banerjee S, Newman RA, Bueso-Ramos CE, Price JE. Curcumin suppresses the paclitaxel-induced nuclear factor-kappaB pathway in breast cancer cells and inhibits lung metastasis of human breast cancer in nude mice. Clin Cancer Res. 2005;11:7490–8.CrossRefPubMedGoogle Scholar
  5. 5.
    Bharti AC, Donato N, Aggarwal BB. Curcumin (diferuloylmethane) inhibits constitutive and IL-6-inducible STAT3 phosphorylation in human multiple myeloma cells. J Immunol. 2003;171:3863–71.CrossRefPubMedGoogle Scholar
  6. 6.
    Shishodia S, Singh T, Chaturvedi MM. Modulation of transcription factors by curcumin. Adv Exp Med Biol. 2007;595:127–48.CrossRefPubMedGoogle Scholar
  7. 7.
    Ryu MJ, Cho M, Song JY, Yun YS, Choi IW, Kim DE, Park BS, Oh S. Natural derivatives of curcumin attenuate the Wnt/beta-catenin pathway through down-regulation of the transcriptional coactivator p300. Biochem Biophys Res Commun. 2008;377:1304–8.CrossRefPubMedGoogle Scholar
  8. 8.
    Nemmar A, Subramaniyan D, Ali BH. Protective effect of curcumin on pulmonary and cardiovascular effects induced by repeated exposure to diesel exhaust particles in mice. PLoS One. 2012;7:e39554.CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Kanai M, Imaizumi A, Otsuka Y, Sasaki H, Hashiguchi M, Tsujiko K, Matsumoto S, Ishiguro H, Chiba T. Dose-escalation and pharmacokinetic study of nanoparticle curcumin, a potential anticancer agent with improved bioavailability, in healthy human volunteers. Cancer Chemother Pharmacol. 2012;69:65–70.CrossRefPubMedGoogle Scholar
  10. 10.
    Guimarães MR, de Aquino SG, Coimbra LS, Spolidorio LC, Kirkwood KL, Rossa C Jr. Curcumin modulates the immune response associated with LPS-induced periodontal disease in rats. Innate Immun. 2012;18:155–63.CrossRefPubMedGoogle Scholar
  11. 11.
    Gu Y, Lee HM, Napolitano N, Clemens M, Zhang Y, Sorsa T, Zhang Y, Johnson F, Golub LM. 4-methoxycarbonyl curcumin: a unique inhibitor of both inflammatory mediators and periodontal inflammation. Mediators Inflamm. 2013;2013:329740.CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Elburki MS, Rossa C, Guimaraes MR, Goodenough M, Lee HM, Curylofo FA, Zhang Y, Johnson F, Golub LM. A novel chemically modified curcumin reduces severity of experimental periodontal disease in rats: initial observations. Mediators Inflamm. 2014;2014:959471.CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Gottumukkala SN, Sudarshan S, Mantena SR. Comparative evaluation of the efficacy of two controlled release devices: chlorhexidine chips and indigenous curcumin based collagen as local drug delivery systems. Contemp Clin Dent. 2014;5:175–81.CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Bhatia M, Urolagin SS, Pentyala KB, Urolagin SB, K B M, Bhoi S. Novel therapeutic approach for the treatment of periodontitis by curcumin. J Clin Diagn Res. 2014;8(12):ZC65–9. Scholar
  15. 15.
    Buduneli N, Kinane DF. Host-derived diagnostic markers related to soft tissue destruction and bone degradation in periodontitis. J Clin Periodontol. 2011;38:85–105.CrossRefGoogle Scholar
  16. 16.
    Sorsa T, Mäntylä P, Tervahartiala T, Pussinen PJ, Gamonal J, Hernandez M. MMP activation in diagnostics of periodontitis and systemic inflammation. J Clin Periodontol. 2011;38:817–9.CrossRefPubMedGoogle Scholar
  17. 17.
    Butler GS, Overall CM. Matrix metalloproteinase processing of signaling molecules to regulate inflammation. Periodontol. 2000;2013(63):123–48.Google Scholar
  18. 18.
    Heikkinen AM, Sorsa T, Pitkäniemi J, Tervahartiala T, Kari K, Broms U, Koskenvuo M, Meurman JH. Smoking affects diagnostic salivary periodontal disease biomarker levels in adolescents. J Periodontol. 2010;81:1299–307.CrossRefGoogle Scholar
  19. 19.
    Ingman T, Sorsa T, Lindy O, Koski H, Konttinen YT. Multiple forms of gelatinases/type IV collagenases in saliva and gingival crevicular fluid of periodontitis patients. J Clin Periodontol. 1994;21:26–31.CrossRefPubMedGoogle Scholar
  20. 20.
    Franco C, Patricia HR, Timo S, Claudia B, Marcela H. Matrix metalloproteinases as regulators of periodontal inflammation. Int J Mol Sci. 2017. Scholar
  21. 21.
    Takai R, Uehara O, Harada F, Utsunomiya M, Chujo T, Yoshida K, Sato J, Nishimura M, Chiba I, Abiko Y. DNA hypermethylation of extracellular matrix-related genes in human periodontal fibroblasts induced by stimulation for a prolonged period with lipopolysaccharide derived from Porphyromonas gingivalis. J Periodontal Res. 2016;51:508–17.CrossRefPubMedGoogle Scholar
  22. 22.
    Li S, Li C, Ryu HH, Lim SH, Jang WY, Jung S. Bacitracin inhibits the migration of U87-MG glioma cells via interferences of the integrin outside-in signaling pathway. J Korean Neurosurg Soc. 2016;59:106–16.CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Jiang H, Deng Y, Wang T, Ma J, Li P, Tian P, Han C, Ma X. Interleukin-23 may contribute to the pathogenesis of lumbar disc herniation through the IL-23/IL-17 pathway. J Orthop Surg Res. 2016;11:12.CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Chen KC, Wang YS, Hu CY, Chang WC, Liao YC, Dai CY, Juo SH. OxLDL up-regulates microRNA-29b, leading to epigenetic modifications of MMP-2/MMP-9 genes: a novel mechanism for cardiovascular diseases. FASEB J. 2011;25:1718–28.CrossRefPubMedGoogle Scholar
  25. 25.
    Scrideli CA, Cortez MA, Yunes JA, Queiróz RG, Valera ET, da Mata JF, Toledo SR, Pavoni-Ferreira P, Lee ML, Petrilli AS, Brandalise SR, Tone LG. mRNA expression of matrix metalloproteinases (MMPs) 2 and 9 and tissue inhibitor of matrix metalloproteinases (TIMPs) 1 and 2 in childhood acute lymphoblastic leukemia: potential role of TIMP1 as an adverse prognostic factor. Leuk Res. 2010;34:32–7.CrossRefPubMedGoogle Scholar
  26. 26.
    Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods. 2001;25:402–8.CrossRefGoogle Scholar
  27. 27.
    Moghadamtousi SZ, Kadir HA, Hassandarvish P, Tajik H, Abubakar S, Zandi K. A review on antibacterial, antiviral, and antifungal activity of curcumin. Biomed Res Int. 2014;2014:186864.PubMedGoogle Scholar
  28. 28.
    Tseng YH, Chang KW, Liu CJ, Lin CY, Yang SC, Lin SC. Areca nut extract represses migration and differentiation while activating matrix metalloproteinase-9 of normal gingival epithelial cells. J Periodontal Res. 2008;43:490–9.PubMedGoogle Scholar
  29. 29.
    Chen D, Nie M, Fan MW, Bian Z. Anti-inflammatory activity of curcumin in macrophages stimulated by lipopolysaccharides from Porphyromonas gingivalis. Pharmacology. 2008;82:264–9.CrossRefPubMedGoogle Scholar
  30. 30.
    Smith PC, Santibañez JF, Morales JP, Martinez J. Epidermal growth factor stimulates urokinase-type plasminogen activator expression in human gingival fibroblasts. Possible modulation by genistein and curcumin. J Periodontal Res. 2004;39:380–7.CrossRefPubMedGoogle Scholar
  31. 31.
    Jabłońska-Trypuć A, Matejczyk M, Rosochacki S. Matrix metalloproteinases (MMPs), the main extracellular matrix (ECM) enzymes in collagen degradation, as a target for anticancer drugs. J Enzyme Inhib Med Chem. 2016;31:177–83.CrossRefGoogle Scholar
  32. 32.
    Lu LC, Yang CW, Hsieh WY, Chuang WH, Lin YC, Lin CS. Decreases in plasma MMP-2/TIMP-2 and MMP-9/TIMP-1 ratios in uremic patients during hemodialysis. Clin Exp Nephrol. 2016;20:934–42.CrossRefPubMedGoogle Scholar

Copyright information

© The Society of The Nippon Dental University 2019

Authors and Affiliations

  • Seiko Toraya
    • 1
  • Osamu Uehara
    • 1
  • Daichi Hiraki
    • 2
  • Fumiya Harada
    • 3
  • Puja Neopane
    • 2
  • Tetsuro Morikawa
    • 2
  • Rie Takai
    • 4
  • Koki Yoshida
    • 2
  • Hirofumi Matsuoka
    • 2
  • Nobuyoshi Kitaichi
    • 5
  • Itsuo Chiba
    • 1
  • Yoshihiro Abiko
    • 2
    Email author
  1. 1.Division of Disease Control and Molecular Epidemiology, Department of Oral Growth and Development, School of DentistryHealth Sciences University of HokkaidoHokkaidoJapan
  2. 2.Division of Oral Medicine and Pathology, Department of Human Biology and Pathophysiology, School of DentistryHealth Sciences University of HokkaidoHokkaidoJapan
  3. 3.Division of Oral and Maxillofacial Surgery, Department of Human Biology and Pathophysiology, School of DentistryHealth Sciences University of HokkaidoHokkaidoJapan
  4. 4.The Research Institute of Health SciencesHealth Sciences University of HokkaidoHokkaidoJapan
  5. 5.Department of OphthalmologyHealth Sciences University of Hokkaido HospitalHokkaidoJapan

Personalised recommendations