Skip to main content

Advertisement

Log in

Inhibitory Effects of Ginkgo biloba Extract on Inflammatory Mediator Production by Porphyromonas gingivalis Lipopolysaccharide in Murine Macrophages via Nrf-2 Mediated Heme Oxygenase-1 Signaling Pathways

  • Published:
Inflammation Aims and scope Submit manuscript

Abstract

Periodontitis is an oral chronic inflammatory disease that influences systemic diseases. Heme oxygenase-1 has several beneficial abilities through Nrf-2 regulation. Ginkgo biloba has been reported to have anti-inflammatory effects associated with heme oxygenase-1 (HO-1) expression. In this study, we investigated whether the anti-inflammatory effects of G. biloba were involved with Nrf-2-mediated HO-1 expression in Porphyromonas gingivalis LPS-stimulated RAW264.7 macrophage cells. G. biloba was extracted with ethyl acetate (EGB). EGB exhibited anti-inflammatory activities, which suppressed the production of pro-inflammatory mediators, the activation of mitogen-activated protein kinases, and nuclear translocation of transcription factors. EGB also up-regulated the HO-1 expression, and the Nrf-2 level in the nucleus and its transactivity. Furthermore, reduced pro-inflammatory mediator levels by EGB were inverted in the presence of SnPP. The collective results suggest that the anti-inflammatory effects of EGB are due to the HO-1 expression via up-regulation of Nrf-2 in RAW 264.7 cells stimulated by P. gingivalis LPS.

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

Access this article

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

Instant access to the full article PDF.

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

Similar content being viewed by others

References

  1. Tanner, A., R. Kent, M.F. Maiden, and M.A. Taubman. 1996. Clinical, microbiological and immunological profile of healthy, gingivitis and putative active periodontal subjects. Journal of Periodontal Research 31: 195–204.

    Article  PubMed  CAS  Google Scholar 

  2. Seymour, G.J., P.J. Ford, M.P. Cullinan, S. Leishman, and K. Yamazaki. 2007. Relationship between periodontal infections and systemic disease. Clinical Microbiology and Infection 13: 3–10.

    Article  PubMed  CAS  Google Scholar 

  3. Cullinan, M.P., P.J. Ford, and G.J. Seymour. 2009. Periodontal disease and systemic health: current status. Australian Dental Journal 54: S62–S69.

    Article  PubMed  Google Scholar 

  4. Chen, J.S., P.H. Huang, C.H. Wang, F.Y. Lin, H.Y. Tsai, T.C. Wu, S.J. Lin, and J.W. Chen. 2011. Nrf-2 mediated heme oxygenase-1 expression, an antioxidant-independent mechanism, contributes to anti-atherogenesis and vascular protective effects of Ginkgo biloba extract. Atherosclerosis 214: 301–309.

    Article  PubMed  CAS  Google Scholar 

  5. Shah, Z.A., S.E. Nada, and S. Dore. 2011. Heme oxygenase 1, beneficial role in permanent ischemic stroke and in Gingko biloba (EGb 761) neuroprotection. Neuroscience 180: 248–255.

    Article  PubMed  CAS  Google Scholar 

  6. Singh, B., P. Kaur, R.D.Singh Gopichand, and P.S. Ahuja. 2008. Biology and chemistry of Ginkgo biloba. Fitoterapia 79: 401–418.

    Article  PubMed  CAS  Google Scholar 

  7. Osawa, K., T. Matsumoto, H. Yasuda, T. Kato, Y. Naito, and K. Okuda. 1991. The inhibitory effect of plant extracts on the collagenolytic activity and cytotoxicity of human gingival fibroblasts by Porphyromonas gingivalis crude enzyme. Bulletin of Tokyo Dental College 32: 1–7.

    PubMed  CAS  Google Scholar 

  8. Maitra, I., L. Marcocci, M.T. Droy-Lefaix, and L. Packer. 1995. Peroxyl radical scavenging activity of Ginkgo biloba extract EGb 761. Biochemical Pharmacology 49: 1649–1655.

    Article  PubMed  CAS  Google Scholar 

  9. Liu, X.P., C.E. Goldring, I.M. Copple, H.Y. Wang, W. Wei, N.R. Kitteringham, and B.K. Park. 2007. Extract of Ginkgo biloba induces phase 2 genes through Keap1-Nrf2-ARE signaling pathway. Life Science 80: 1586–1591.

    Article  CAS  Google Scholar 

  10. Maines, M.D. 1997. The heme oxygenase system: a regulator of second messenger gases. Annual Review of Pharmacology and Toxicology 37: 517–554.

    Article  PubMed  CAS  Google Scholar 

  11. Otterbein, L.E., F.H. Bach, J. Alam, M. Soares, H. Tao Lu, M. Wysk, R.J. Davis, R.A. Flavell, and A.M. Choi. 2000. Carbon monoxide has anti-inflammatory effects involving the mitogen-activated protein kinase pathway. Nature Medicine 6: 422–428.

    Article  PubMed  CAS  Google Scholar 

  12. Llesuy, S.F., and M.L. Tomaro. 1994. Heme oxygenase and oxidative stress. Evidence of involvement of bilirubin as physiological protector against oxidative damage. Biochimica et Biophysica Acta 1223: 9–14.

    CAS  Google Scholar 

  13. Itoh, K., N. Wakabayashi, Y. Katoh, T. Ishii, K. Igarashi, J.D. Engel, and M. Yamamoto. 1999. Keap1 represses nuclear activation of antioxidant responsive elements by Nrf2 through binding to the amino-terminal Neh2 domain. Genes and Development 13: 76–86.

    Article  PubMed  CAS  Google Scholar 

  14. Itoh, K., K.I. Tong, and M. Yamamoto. 2004. Molecular mechanism activating Nrf2-Keap1 pathway in regulation of adaptive response to electrophiles. Free Radical Biology and Medicine 36: 1208–1213.

    Article  PubMed  CAS  Google Scholar 

  15. Turcanu, V., M. Dhouib, and P. Poindron. 1998. Determination of heme oxygenase activity in murine macrophages for studying oxidative stress inhibitors. Analytical Biochemistry 263: 251–53.

    Article  PubMed  CAS  Google Scholar 

  16. Rose, D.M., B.W. Winston, E.D. Chan, D.W. Riches, P. Gerwins, G.L. Johnson, and P.M. Henson. 1997. Fc gamma receptor cross-linking activates p42, p38, and JNK/SAPK mitogen-activated protein kinases in murine macrophages: Role for p42MAPK in Fc gamma receptor-stimulated TNF-alpha synthesis. Journal of Immunology 158: 3433–3438.

    CAS  Google Scholar 

  17. Yoshimura, A., Y. Hara, T. Kaneko, and I. Kato. 1997. Secretion of IL-1 beta, TNF-alpha, IL-8 and IL-1ra by human polymorphonuclear leukocytes in response to lipopolysaccharides from periodontopathic bacteria. Journal of Periodontal Research 32: 279–286.

    Article  PubMed  CAS  Google Scholar 

  18. Morse, D., S.E. Pischke, Z. Zhou, R.J. Davis, R.A. Flavell, T. Loop, S.L. Otterbein, L.E. Otterbein, and A.M. Choi. 2003. Suppression of inflammatory cytokine production by carbon monoxide involves the JNK pathway and AP-1. Journal of Biological Chemistry 278: 36993–36998.

    Article  PubMed  CAS  Google Scholar 

  19. Hess, J., P. Angel, and M. Schorpp-Kistner. 2004. AP-1 subunits: Quarrel and harmony among siblings. Journal of Cell Science 117: 5965–5973.

    Article  PubMed  CAS  Google Scholar 

  20. Morimoto, Y., K. Kikuchi, T. Ito, M. Tokuda, T. Matsuyama, S. Noma, T. Hashiguchi, M. Torii, I. Maruyama, and K. Kawahara. 2009. MK615 attenuates Porphyromonas gingivalis lipopolysaccharide-induced pro-inflammatory cytokine release via MAPK inactivation in murine macrophage-like RAW264.7 cells. Biochemical and Biophysical Research Communications 389: 90–94.

    Article  PubMed  CAS  Google Scholar 

  21. Jain, S., and R.P. Darveau. 2010. Constribution of Porphyromonas gingivalis lipopolysaccharide to periodontitis. Periodontology 2000(54): 53–70.

    Article  Google Scholar 

  22. Bainbridge, B.W., and R.P. Darveau. 2001. Porphyromonas gingivalis lipopolysaccharide:an unusual pattern recognition receptor ligand for the innate host defense system. Acta odontologica Scandinavica 59: 131–138.

    Article  PubMed  CAS  Google Scholar 

  23. Martin, M., J. Katz, S.N. Vogel, and S.M. Michalek. 2001. Differential induction of endotoxin tolerance by lipopolysaccharides derived from Porphyromonas gingivalis and Escherichia coli. Journal of Immunology 167: 5278–5285.

    CAS  Google Scholar 

  24. Kotakadi, V.S., Y. Jin, A.B. Hofseth, L. Ying, et al. 2008. Ginkgo biloba extract EGb 761 has anti-inflammatory properties and ameliorates colitis in mice by driving effector T cell apoptosis. Carcinogenesis 29: 1799–1806.

    Article  PubMed  CAS  Google Scholar 

  25. Yao, P., K. Li, F. Song, S. Zhou, X. Sun, X. Zhang, A.K. Nussler, and L. Liu. 2007. Heme oxygenase-1 upregulated by Ginkgo biloba extract: potential protection against ethanol-induced oxidative liver damage. Food and Chemical Toxicology 45: 1333–1342.

    Article  PubMed  CAS  Google Scholar 

  26. Chan, P.C., Q. Xia, and P.P. Fu. 2007. Ginkgo biloba leave extract: biological, medicinal, and toxicological effects. Journal of Environmental Science and Health Part C Environmental Carcinogenesis & Ecotoxicology Reviews 25: 211–244.

    Article  CAS  Google Scholar 

  27. Riemenschneider, W. and H.M. Bolt. 2000. Esters, organic. In Ullmann's encyclopedia of industrial chemistry (Anonymous). Wiley-VCH Verlag GmbH & Co. KGaA.

  28. Yu, M., H. Li, Q. Liu, F. Liu, et al. 2011. Nuclear factor p65 interacts with Keap1 to repress the Nrf2-ARE pathway. Cell Signaling 23: 883–892.

    Article  CAS  Google Scholar 

  29. Salari, M.H., and Z. Kadkhoda. 2004. Rate of cultivable subgingival periodontopathogenic bacteria in chronic periodontitis. Journal of Oral Science 46(3): 157–161.

    Article  PubMed  Google Scholar 

  30. Griffen, A.L., M.R. Becker, S.R. Lyons, M.L. Moeschberger, and E.J. Leys. 1998. Prevalence of Porphyromonas gingivalis and periodontal health status. Journal of Vlinical microbiology 36: 3239–3242.

    CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Sang-Joon Lee.

Additional information

E.Y. Ryu and A.J. Park have contributed equally to this work.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ryu, E.Y., Park, A.J., Park, S.Y. et al. Inhibitory Effects of Ginkgo biloba Extract on Inflammatory Mediator Production by Porphyromonas gingivalis Lipopolysaccharide in Murine Macrophages via Nrf-2 Mediated Heme Oxygenase-1 Signaling Pathways. Inflammation 35, 1477–1486 (2012). https://doi.org/10.1007/s10753-012-9461-6

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10753-012-9461-6

KEY WORDS

Navigation