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Erschienen in: Inflammation 4/2012

01.08.2012

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

verfasst von: Eun Yeon Ryu, Ah Jeong Park, Sun Young Park, Sung Hae Park, Hye Won Eom, Young Hun Kim, Geuntae Park, Sang-Joon Lee

Erschienen in: Inflammation | Ausgabe 4/2012

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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.
Literatur
1.
Zurück zum Zitat 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.PubMedCrossRef 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.PubMedCrossRef
2.
Zurück zum Zitat 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.PubMedCrossRef 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.PubMedCrossRef
3.
Zurück zum Zitat Cullinan, M.P., P.J. Ford, and G.J. Seymour. 2009. Periodontal disease and systemic health: current status. Australian Dental Journal 54: S62–S69.PubMedCrossRef Cullinan, M.P., P.J. Ford, and G.J. Seymour. 2009. Periodontal disease and systemic health: current status. Australian Dental Journal 54: S62–S69.PubMedCrossRef
4.
Zurück zum Zitat 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.PubMedCrossRef 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.PubMedCrossRef
5.
Zurück zum Zitat 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.PubMedCrossRef 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.PubMedCrossRef
6.
Zurück zum Zitat Singh, B., P. Kaur, R.D.Singh Gopichand, and P.S. Ahuja. 2008. Biology and chemistry of Ginkgo biloba. Fitoterapia 79: 401–418.PubMedCrossRef Singh, B., P. Kaur, R.D.Singh Gopichand, and P.S. Ahuja. 2008. Biology and chemistry of Ginkgo biloba. Fitoterapia 79: 401–418.PubMedCrossRef
7.
Zurück zum Zitat 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 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
8.
Zurück zum Zitat 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.PubMedCrossRef 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.PubMedCrossRef
9.
Zurück zum Zitat 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.CrossRef 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.CrossRef
10.
Zurück zum Zitat Maines, M.D. 1997. The heme oxygenase system: a regulator of second messenger gases. Annual Review of Pharmacology and Toxicology 37: 517–554.PubMedCrossRef Maines, M.D. 1997. The heme oxygenase system: a regulator of second messenger gases. Annual Review of Pharmacology and Toxicology 37: 517–554.PubMedCrossRef
11.
Zurück zum Zitat 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.PubMedCrossRef 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.PubMedCrossRef
12.
Zurück zum Zitat 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. 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.
13.
Zurück zum Zitat 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.PubMedCrossRef 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.PubMedCrossRef
14.
Zurück zum Zitat 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.PubMedCrossRef 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.PubMedCrossRef
15.
Zurück zum Zitat 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.PubMedCrossRef 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.PubMedCrossRef
16.
Zurück zum Zitat 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. 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.
17.
Zurück zum Zitat 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.PubMedCrossRef 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.PubMedCrossRef
18.
Zurück zum Zitat 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.PubMedCrossRef 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.PubMedCrossRef
19.
Zurück zum Zitat Hess, J., P. Angel, and M. Schorpp-Kistner. 2004. AP-1 subunits: Quarrel and harmony among siblings. Journal of Cell Science 117: 5965–5973.PubMedCrossRef Hess, J., P. Angel, and M. Schorpp-Kistner. 2004. AP-1 subunits: Quarrel and harmony among siblings. Journal of Cell Science 117: 5965–5973.PubMedCrossRef
20.
Zurück zum Zitat 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.PubMedCrossRef 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.PubMedCrossRef
21.
Zurück zum Zitat Jain, S., and R.P. Darveau. 2010. Constribution of Porphyromonas gingivalis lipopolysaccharide to periodontitis. Periodontology 2000(54): 53–70.CrossRef Jain, S., and R.P. Darveau. 2010. Constribution of Porphyromonas gingivalis lipopolysaccharide to periodontitis. Periodontology 2000(54): 53–70.CrossRef
22.
Zurück zum Zitat 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.PubMedCrossRef 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.PubMedCrossRef
23.
Zurück zum Zitat 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. 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.
24.
Zurück zum Zitat 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.PubMedCrossRef 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.PubMedCrossRef
25.
Zurück zum Zitat 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.PubMedCrossRef 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.PubMedCrossRef
26.
Zurück zum Zitat 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.CrossRef 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.CrossRef
27.
Zurück zum Zitat Riemenschneider, W. and H.M. Bolt. 2000. Esters, organic. In Ullmann's encyclopedia of industrial chemistry (Anonymous). Wiley-VCH Verlag GmbH & Co. KGaA. Riemenschneider, W. and H.M. Bolt. 2000. Esters, organic. In Ullmann's encyclopedia of industrial chemistry (Anonymous). Wiley-VCH Verlag GmbH & Co. KGaA.
28.
Zurück zum Zitat 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.CrossRef 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.CrossRef
29.
Zurück zum Zitat Salari, M.H., and Z. Kadkhoda. 2004. Rate of cultivable subgingival periodontopathogenic bacteria in chronic periodontitis. Journal of Oral Science 46(3): 157–161.PubMedCrossRef Salari, M.H., and Z. Kadkhoda. 2004. Rate of cultivable subgingival periodontopathogenic bacteria in chronic periodontitis. Journal of Oral Science 46(3): 157–161.PubMedCrossRef
30.
Zurück zum Zitat 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. 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.
Metadaten
Titel
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
verfasst von
Eun Yeon Ryu
Ah Jeong Park
Sun Young Park
Sung Hae Park
Hye Won Eom
Young Hun Kim
Geuntae Park
Sang-Joon Lee
Publikationsdatum
01.08.2012
Verlag
Springer US
Erschienen in
Inflammation / Ausgabe 4/2012
Print ISSN: 0360-3997
Elektronische ISSN: 1573-2576
DOI
https://doi.org/10.1007/s10753-012-9461-6

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