Skip to main content

Advertisement

SpringerLink
Log in

Moutan Cortex Radicis inhibits inflammatory changes of gene expression in lipopolysaccharide-stimulated gingival fibroblasts

  • Original Paper
  • Published:
Journal of Natural Medicines Aims and scope Submit manuscript

Abstract

Moutan Cortex Radicis (MCR), the root bark of Paeonia suffruticosa Andrews (Paeoniaceae), is found in the traditional Chinese medicinal formulae which were used to treat periodontal diseases. This study investigated the changes in gene expression by MCR treatment when stimulated with lipopolysaccharide (LPS) in cultured human gingival fibroblasts (HGFs). A genome-wide expression GeneChip was used for the gene array analysis, and real-time reverse transcription polymerase chain reaction (RT-PCR) analysis was also performed to confirm the gene expression. It was shown that 42 of the 643 genes up-regulated by LPS, when compared to the control, were down-regulated by the MCR treatment. Of these 42 genes, the inflammation and immune response-related genes were especially noted, which indicates that MCR inhibits the induction of inflammation by LPS stimulation. In addition, 33 of the 519 genes down-regulated by LPS, when compared to the control, were up-regulated by the MCR treatment. The expression patterns of some representative genes by real-time RT-PCR correlated with those of the genes shown in the microarray. In addition, the MCR extract contained paeonol and paeoniflorin, which are known to have the anti-inflammatory effect as the major phenolic components of MCR. This study showed that the MCR extract could comprehensively inhibit a wide variety of activations of inflammation-related genes, which may be due to paeonol and paeoniflorin. It is, thus, suggested that MCR may be applied to alleviate the inflammation of periodontal diseases.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Sheehan MP, Atherton DJ (1994) One-year follow up of children treated with Chinese medicinal herbs for atopic eczema. Br J Dermatol 130:488–493

    Article  PubMed  CAS  Google Scholar 

  2. Lin HC, Ding HY, Wu YC (1998) Two novel compounds from Paeonia suffructicosa. J Nat Prod 61:343–346

    Article  PubMed  CAS  Google Scholar 

  3. Ding HY, Wu YC, Lin HC, Chan YY, Wu PL, Wu TS (1999) Glycosides from Paeonia suffruticosa. Chem Pharm Bull 47:652–655

    Article  CAS  Google Scholar 

  4. Hsiang CY, Hsieh CL, Wu SL, Lai IL, Ho TY (2001) Inhibitory effect of anti-pyretic and anti-inflammatory herbs on herpes simplex virus replication. Am J Chin Med 29:459–467

    Article  PubMed  CAS  Google Scholar 

  5. Au TK, Lam TL, Ng TB, Fong WP, Wan DC (2001) A comparison of HIV-1 integrase inhibition by aqueous and methanol extracts of Chinese medicinal herbs. Life Sci 68:1687–1694

    Article  PubMed  CAS  Google Scholar 

  6. Oh GS, Pae HO, Choi BM, Jeong S, Oh H, OH CS, Rho YD, Kim DH, Shin MK, Chung HT (2003) Inhibitory effects of the root cortex of Paeonia suffruticosa on interleukin-8 and macrophage chemoattractant protein-1 secretions in U937 cells. J Ethnopharmacol 84:85–89

    Article  PubMed  CAS  Google Scholar 

  7. Rho S, Chung HS, Kang M, Lee E, Cho C, Kim H, Park S, Kim HY, Hong M, Shin M, Bae H (2005) Inhibition of production of reactive oxygen species and gene expression profile by treatment of ethanol extract of Moutan Cortex Radicis in oxidative stressed PC12 cells. Biol Pharm Bull 28:661–666

    Article  PubMed  CAS  Google Scholar 

  8. Hong MH, Kim JH, Na SH, Bae H, Shin YC, Kim SH, Ko SG (2010) Inhibitory effects of Paeonia suffruticosa on allergic reactions by inhibiting the NF-kappaB/I kappaB-alpha signaling pathway and phosphorylation of ERK in an animal model and human mast cells. Biosci Biotechnol Biochem 74:1152–1156

    Article  PubMed  CAS  Google Scholar 

  9. Haffajee AD, Socransky SS (1994) Microbial etiological agents of destructive periodontal diseases. Periodontol 5:78–111

    Article  CAS  Google Scholar 

  10. Jenkinson HF, Dymock D (1999) The microbiology of periodontal disease. Dent Update 26:191–197

    PubMed  CAS  Google Scholar 

  11. Page RC (1999) Milestones in periodontal research and the remaining critical issues. J Periodontal Res 34:331–339

    Article  PubMed  CAS  Google Scholar 

  12. Kinane DF, Lappin DF (2002) Immune processes in periodontal disease: a review. Ann Periodontol 7:62–71

    Article  PubMed  Google Scholar 

  13. Hosokawa Y, Hosokawa I, Ozaki K, Nakae H, Matsuo T (2009) Cytokines differentially regulate CXCL10 production by interferon-gamma-stimulated or tumor necrosis factor-alpha-stimulated human gingival fibroblasts. J Periodontal Res 44:225–231

    Article  PubMed  CAS  Google Scholar 

  14. Daghigh F, Borghaei RC, Thornton RD, Bee JH (2002) Human gingival fibroblasts produce nitric oxide in response to proinflammatory cytokines. J Periodontol 37:392–400

    Article  Google Scholar 

  15. Wang PL, Ohura K, Fujii T, Oido-Mori M, Kowashi Y, Kikuchi M, Suetsugu Y, Tanaka J (2003) DNA microarray analysis of human gingival fibroblasts from healthy and inflammatory gingival tissues. Biochem Biophys Res Commun 305:970–973

    Article  PubMed  CAS  Google Scholar 

  16. Takashiba S, Takigawa M, Takahashi K, Myokai F, Nishimura F, Chihara T, Kurihara H, Nomura Y, Murayama Y (1992) Interleukin-8 is a major neutrophil chemotactic factor derived from cultured human gingival fibroblasts stimulated with interleukin-1 beta or tumor necrosis factor alpha. Infect Immun 60:5253–5258

    PubMed  CAS  Google Scholar 

  17. Sakuta T, Tokuda M, Tamura M, Jimi E, Ikebe T, Koba T, Nagaoka S, Takada H (1998) Dual regulatory effects of interferon-alpha, -beta, and -gamma on interleukin-8 gene expression by human gingival fibroblasts in culture upon stimulation with lipopolysaccharide from Prevotella intermedia, interleukin-1alpha, or tumor necrosis factor-alpha. J Dent Res 77:1597–1605

    Article  PubMed  CAS  Google Scholar 

  18. Shimabukuro Y, Murakami S, Okada H (1996) Antigen-presenting-cell function of interferon gamma-treated human gingival fibroblasts. J Periodontal Res 31:217–228

    Article  PubMed  CAS  Google Scholar 

  19. Okada H, Murakami S (1998) Cytokine expression in periodontal health and disease. Crit Rev Oral Biol Med 9:248–266

    Article  PubMed  CAS  Google Scholar 

  20. Offenbacher S (1996) Periodontal diseases: pathogenesis. Ann Periodontal 1:821–878

    Article  CAS  Google Scholar 

  21. Lamont RJ, Jenkinson HF (1998) Life below the gum line: pathogenic mechanisms of Porphyromonas gingivalis. Microbiol Mol Biol Rev 62:1244–1263

    PubMed  CAS  Google Scholar 

  22. Nygaard V, Hovig E (2009) Methods for quantitation of gene expression. Front Biosci 14:552–569

    Article  PubMed  CAS  Google Scholar 

  23. Ha KCh, Coulombe-Huntington J, Majewski J (2009) Comparison of Affymetrix Gene Array with the Exon Array shows potential application for detection of transcript isoform variation. BMC Genomics 10:519

    Article  PubMed  Google Scholar 

  24. Jeong MY, Kim YH, Lee NK, Lee JY, Herr Y, Lee JH, Lim S (2008) Antimicrobial effect on the periodontal pathogens and anti-inflammatory effect of Eriobotryae Folium. J Korean Orient Med 29:182–192 (in Korean)

    Google Scholar 

  25. An JH, Lee SY, Jeon JY, Cho KG, Kim SU, Lee MA (2009) Identification of gliotropic factors that induce human stem cell migration to malignant tumor. J Proteome Res 8:2873–2881

    Article  PubMed  CAS  Google Scholar 

  26. Kim SH, Kim SA, Park MK, Kim SH, Park YD, Na HJ, Kim HM, Shin MK, Ahn KS (2004) Paeonol inhibits anaphylactic reaction by regulating histamine and TNF-alpha. Int Immunopharmacol 4:279–287

    Article  PubMed  CAS  Google Scholar 

  27. Booth V, Keizer DW, Kamphuis MB, Clark-Lewis I, Sykes BD (2002) The CXCR3 binding chemokine IP-10/CXCL10: structure and receptor interactions. Biochemistry 41:10418–10425

    Article  PubMed  CAS  Google Scholar 

  28. Angiolillo AL, Sgadari C, Taub DD, Liao F, Farber JM, Maheshwari S, Kleinman HK, Reaman GH, Tosato G (1995) Human interferon-inducible protein 10 is a potent inhibitor of angiogenesis in vivo. J Exp Med 182:155–162

    Article  PubMed  CAS  Google Scholar 

  29. Dufour JH, Dziejman M, Liu MT, Leung JH, Lane TE, Luster AD (2002) IFN-gamma-inducible protein 10 (IP-10; CXCL10)-deficient mice reveal a role for IP-10 in effector T cell generation and trafficking. J Immunol 168:3195–3204

    PubMed  CAS  Google Scholar 

  30. Tensen CP, Flier J, Van Der Raaij-Helmer EM, Sampat-Sardjoepersad S, Van Der Schors RC, Leurs R, Scheper RJ, Boorsma DM, Willemze R (1999) Human IP-9: a keratinocyte-derived high affinity CXC-chemokine ligand for the IP-10/Mig receptor (CXCR3). J Invest Dermatol 112:716–722

    Article  PubMed  CAS  Google Scholar 

  31. Rani MR, Foster GR, Leung S, Leaman D, Stark GR, Ransohoff RM (1996) Characterization of beta-R1, a gene that is selectively induced by interferon beta (IFN-beta) compared with IFN-alpha. J Biol Chem 271:22878–22884

    Article  PubMed  CAS  Google Scholar 

  32. Cole KE, Strick CA, Paradis TJ, Ogborne KT, Loetscher M, Gladue RP, Lin W, Boyd JG, Moser B, Wood DE, Sahagan BG, Neote K (1998) Interferon-inducible T cell alpha chemoattractant (I-TAC): a novel non-ELR CXC chemokine with potent activity on activated T cells through selective high affinity binding to CXCR3. J Exp Med 187:2009–2021

    Article  PubMed  CAS  Google Scholar 

  33. Qin S, Rottman JB, Myers P, Kassam N, Weinblatt M, Loetscher M, Koch AE, Moser B, Mackay CR (1998) The chemokine receptors CXCR3 and CCR5 mark subsets of T cells associated with certain inflammatory reactions. J Clin Invest 101:746–754

    Article  PubMed  CAS  Google Scholar 

  34. Garlet GP, Martins W Jr, Ferreira BR, Milanezi CM, Silva JS (2003) Patterns of chemokines and chemokine receptors expression in different forms of human periodontal disease. J Periodontal Res 38:210–217

    Article  PubMed  CAS  Google Scholar 

  35. Spandau U, Toksoy A, Goebeler M, Bröcker EB, Gillitzer R (1998) MIG is a dominant lymphocyte-attractant chemokine in lichen planus lesions. J Invest Dermatol 111:1003–1009

    Article  PubMed  CAS  Google Scholar 

  36. Boorsma DM, Flier J, Sampat S, Ottevanger C, de Haan P, Hooft L, Willemze R, Tensen CP, Stoof TJ (1998) Chemokine IP-10 expression in cultured human keratinocytes. Arch Dermatol Res 290:335–341

    Article  PubMed  CAS  Google Scholar 

  37. Villagomez MT, Bae SJ, Ogawa I, Takenaka M, Katayama I (2004) Tumour necrosis factor-alpha but not interferon-gamma is the main inducer of inducible protein-10 in skin fibroblasts from patients with atopic dermatitis. Br J Dermatol 150:910–916

    Article  PubMed  CAS  Google Scholar 

  38. Ohta K, Shigeishi H, Taki M, Nishi H, Higashikawa K, Takechi M, Kamata N (2008) Regulation of CXCL9/10/11 in oral keratinocytes and fibroblasts. J Dent Res 87:1160–1165

    Article  PubMed  CAS  Google Scholar 

  39. Mellor AL, Munn DH (2004) IDO expression by dendritic cells: tolerance and tryptophan catabolism. Nat Rev Immunol 4:762–774

    Article  PubMed  CAS  Google Scholar 

  40. Terness P, Bauer TM, Röse L, Dufter C, Watzlik A, Simon H, Opelz G (2002) Inhibition of allogeneic T cell proliferation by indoleamine 2,3-dioxygenase-expressing dendritic cells: mediation of suppression by tryptophan metabolites. J Exp Med 196:447–457

    Article  PubMed  CAS  Google Scholar 

  41. Ghahary A, Li Y, Tredget EE, Kilani RT, Iwashina T, Karami A, Lin X (2004) Expression of indoleamine 2,3-dioxygenase in dermal fibroblasts functions as a local immunosuppressive factor. J Invest Dermatol 122:953–964

    Article  PubMed  Google Scholar 

  42. Holmes EW (1998) Expression and regulation of interferon-γ-induced tryptophan catabolism in cultured skin fibroblasts. J Interferon Cytokine Res 18:509–520

    Article  PubMed  CAS  Google Scholar 

  43. Sarkhosh K, Tredget EE, Uludag H, Kilani RT, Karami A, Li Y, Iwashina T, Ghahary A (2004) Temperature-sensitive polymer-conjugated IFN-γ induces the expression of IDO mRNA and activity by fibroblasts populated in collagen gel (FPCG). J Cell Physiol 201:146–154

    Article  PubMed  CAS  Google Scholar 

  44. Mahanonda R, Sa-Ard-Iam N, Montreekachon P, Pimkhaokham A, Yongvanichit K, Fukuda MM, Pichyangkul S (2007) IL-8 and IDO expression by human gingival fibroblasts via TLRs. J Immunol 178:1151–1157

    PubMed  CAS  Google Scholar 

  45. Izmailova E, Bertley FM, Huang Q, Makori N, Miller CJ, Young RA, Aldovini A (2003) HIV-1 Tat reprograms immature dendritic cells to express chemoattractants for activated T cells and macrophages. Nat Med 9:191–197

    Article  PubMed  CAS  Google Scholar 

  46. Ahrens I, Domeij H, Eisenhardt SU, Topcic D, Albrecht M, Leitner E, Viitaniemi K, Jowett JB, Lappas M, Bode C, Haviv I, Peter K (2011) Opposing effects of monomeric and pentameric C-reactive protein on endothelial progenitor cells. Basic Res Cardiol 106:879–895

    Article  PubMed  CAS  Google Scholar 

  47. Papenfuss K, Cordier SM, Walczak H (2008) Death receptors as targets for anti-cancer therapy. J Cell Mol Med 12:2566–2585

    Article  PubMed  CAS  Google Scholar 

  48. Wiley SR, Schooley K, Smolak PJ, Din WS, Huang CP, Nicholl JK, Sutherland GR, Smith TD, Rauch C, Smith CA, Goodwin RG (1995) Identification and characterization of a new member of the TNF family that induces apoptosis. Immunity 3:673–682

    Article  PubMed  CAS  Google Scholar 

  49. Pan G, Ni J, Wei YF, Yu G, Gentz R, Dixit VM (1997) An antagonist decoy receptor and a death domain-containing receptor for TRAIL. Science 277:815–818

    Article  PubMed  CAS  Google Scholar 

  50. Sheridan JP, Marsters SA, Pitti RM, Gurney A, Skubatch M, Baldwin D, Ramakrishnan L, Gray CL, Baker K, Wood WI, Goddard AD, Godowski P, Ashkenazi A (1997) Control of TRAIL-induced apoptosis by a family of signaling and decoy receptors. Science 277:818–821

    Article  PubMed  CAS  Google Scholar 

  51. Roberts AI, Devadas S, Zhang X, Zhang L, Keegan A, Greeneltch K, Solomon J, Wei L, Das J, Sun E, Liu C, Yuan Z, Zhou JN, Shi Y (2003) The role of activation-induced cell death in the differentiation of T-helper-cell subsets. Immunol Res 28:285–293

    Article  PubMed  Google Scholar 

  52. Zauli G, Rimondi E, Nicolin V, Melloni E, Celeghini C, Secchiero P (2004) TNF-related apoptosis-inducing ligand (TRAIL) blocks osteoclastic differentiation induced by RANKL plus M-CSF. Blood 104:2044–2050

    Article  PubMed  CAS  Google Scholar 

  53. Lucas H, Bartold PM, Dharmapatni AA, Holding CA, Haynes DR (2010) Inhibition of apoptosis in periodontitis. J Dent Res 89:29–33

    Article  PubMed  CAS  Google Scholar 

  54. Mantovani A, Bonecchi R, Locati M (2006) Tuning inflammation and immunity by chemokine sequestration: decoys and more. Nat Rev Immunol 6:907–918

    Article  PubMed  CAS  Google Scholar 

  55. Wang J, Ou ZL, Hou YF, Luo JM, Shen ZZ, Ding J, Shao ZM (2006) Enhanced expression of Duffy antigen receptor for chemokines by breast cancer cells attenuates growth and metastasis potential. Oncogene 25:7201–7211

    Article  PubMed  CAS  Google Scholar 

  56. Wu FY, Ou ZL, Feng LY, Luo JM, Wang LP, Shen ZZ, Shao ZM (2008) Chemokine decoy receptor d6 plays a negative role in human breast cancer. Mol Cancer Res 6:1276–1288

    Article  PubMed  CAS  Google Scholar 

  57. Feng LY, Ou ZL, Wu FY, Shen ZZ, Shao ZM (2009) Involvement of a novel chemokine decoy receptor CCX-CKR in breast cancer growth, metastasis and patient survival. Clin Cancer Res 15:2962–2970

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

This work was supported by a grant from the Kyung Hee University Post-Doctoral Fellowship in 2010 (KHU-20100429).

Conflict of interest

The authors declare no conflict of interest.

Author information

Authors and Affiliations

  1. Department of Basic Oriental Medical Science, College of Oriental Medicine, Kyung Hee University, #1 Hoegi-dong, Dongdaemun-gu, Seoul, 130-701, Republic of Korea

    Cheol-Sang Yun, Yeong-Gon Choi, Mi-Young Jeong & Sabina Lim

  2. Research Group of Pain and Neuroscience, WHO Collaborating Center for Traditional Medicine, East–West Medical Research Institute, Kyung Hee University, #1 Hoegi-dong, Dongdaemun-gu, Seoul, 130-701, Republic of Korea

    Yeong-Gon Choi, Mi-Young Jeong & Sabina Lim

  3. Department of Herbology, College of Oriental Medicine, Dongguk University, Gyeongju, Republic of Korea

    Je-Hyun Lee

Authors
  1. Cheol-Sang Yun
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yeong-Gon Choi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Mi-Young Jeong
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Je-Hyun Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Sabina Lim
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Sabina Lim.

Additional information

C.-S. Yun and Y.-G. Choi contributed equally to this work.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (XLS 207 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Yun, CS., Choi, YG., Jeong, MY. et al. Moutan Cortex Radicis inhibits inflammatory changes of gene expression in lipopolysaccharide-stimulated gingival fibroblasts. J Nat Med 67, 576–589 (2013). https://doi.org/10.1007/s11418-012-0714-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11418-012-0714-3

Keywords

Search

Navigation