Skip to main content
SpringerLink
Log in

Involvement of T-cell immunoregulation by ochnaflavone in therapeutic effect on fungal arthritis due to Candida albicans

  • Research Articles
  • Drug Actions
  • Published:
Archives of Pharmacal Research Aims and scope Submit manuscript

Abstract

Arthritis due to pathogenic fungi is a serious disease causing rapid destruction of the joint. In the pathogenesis of arthritis, T lymphocytes are considered to be one of the major immune cells. In present study, we examined the T cell immunoregulatory effect by ochnaflavone (Och), a biflavonoid, on arthritis caused by Candida albicans that is the most commonly associated with fungal arthritis. To examine the effects of ochnaflavonon Candida albicans-caused septic arthritis, an emulsified mixture of C. albicans cell wall and complete Freund’s adjuvant (CACW/CFA) was injected into BALB/c mice via hind footpad route on days -3, -2, and -1. On Day 0, Och at 1 or 2 mg/dose/time was intratraperitoneally given to mice with the swollen footpad every other day for 3 times. The footpad-edema was measured for 20 days. Results revealed that Och reduced the edema at all dose levels and furthermore, there was app. 45% reduction of the edema in animals given 2 mg-dose at the peak of septic arthritis (p < 0.05). This anti-arthritic effect was accompanied by the diminishing of the DTH (delayed type hypersensitivity) activity against the CACW and by the provoking of the dominant T helper 2 (Th2) type cytokines production (IL-4 and Il-10), which appeared to result in a suppression of T helper 1 cytokines (IFN-γ and IL-2). Besides the T cell immunoregulatory activity, Och inhibited T cells activation as evidenced by the IL-2 reduction from PMA/ionomycin-stimulated Jurkat cell line and in addition, the compound killed macrophages in a dose-dependent manner (p < 0.05). However, Och caused no hemolysis (p < 0.05). These data implicate that Och, which has anti-arthritic activity based on the Th2 dominance as well as macrophage removal, can be safely administered into the blood circulation for treatment of the arthritis caused by C. albicans. Thus, it can be concluded that Och would be an ideal immunologically evaluated agent for treating of Candida arthritis.

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

Similar content being viewed by others

References

  • Anderson, D., Chambers, K., Hanna, N., Leonard, J., Reff, M., Newman, R., Baldoni, J., Dunleavy, D., Reddy, M., Sweet, R., and Truneh, A., A primatized MAb to human CD4 causes receptor modulation, without marked reduction in CD4+ T cells in chimpanzees: in vitro and in vivo characterization of a MAb (IDEC-CE9.1) to human CD4. Clin. Immunol. Immunopathol., 84, 73–84 (1997).

    Article  PubMed  CAS  Google Scholar 

  • Arnold, H. J., Dini, A., Jonas, G., and Zorn, E. L., Candida albicans arthritis in a healthy adult. South Med. J., 74, 84–85 (1981).

    Article  PubMed  CAS  Google Scholar 

  • Azaceta, G., Olave, T., De Los Martires, L. D., Delgado, C., Gutierrez, M., and Palomera, L., Successful lipid-complexed amphotericin B treatment of Candida arthritis in a lymphoma patient. Rev. Rhum. Engl. Ed., 66, 434–435 (1999).

    PubMed  CAS  Google Scholar 

  • Balcerzak, M., Tyburska, A., and Swiecicka-Füchsel, E., Selective determination of Fe(III) in Fe(II) samples by UV-spectrophotometry with the aid of quercetin and morin. Acta Pharm., 58, 327–334 (2008).

    Article  PubMed  CAS  Google Scholar 

  • Blackham, A. and Griffiths, R. J., The effect of FK506 and cyclosporin A on antigen-induced arthritis. Clin. Exp. Immunol., 86, 224–228 (1991).

    Article  PubMed  CAS  Google Scholar 

  • Boyce, E., Pharmacology of antiarthritic drugs. Clin. Podiatr. Med. Surg., 9, 327–348 (1992).

    PubMed  CAS  Google Scholar 

  • Bräuer, R., Kette, H., Henzgen, S., and Thoss, K., Influence of cyclosporin A on cytokine levels in synovial fluid and serum of rats with antigen-induced arthritis. Agents Actions, 41, 96–98 (1994).

    Article  PubMed  Google Scholar 

  • Brennan, F. M. and Feldmann, M., Cytokines in autoimmunity. Curr. Opin. Immunol., 8, 872–877 (1996).

    Article  PubMed  CAS  Google Scholar 

  • Calvo Romero, J. M., Alvarez Vega, J. L., Salazar Vallinas, J. M., and Ortega Alberdi, R., Candida arthritis in an immunocompetent patient without predisposing factors. Clin. Rheumatol., 17, 393–394 (1998).

    Article  PubMed  CAS  Google Scholar 

  • Feldmann, M., Brennan, F. M., and Maini, R. N., Role of cytokines in rheumatoid arthritis. Annu. Rev. Immunol., 14, 397–440 (1996).

    Article  PubMed  CAS  Google Scholar 

  • Fox, D. A., The role of T cells in the immunopathogenesis of rheumatoid arthritis: new perspective. Arthritis Rheum., 40, 598–609 (1997).

    Article  PubMed  CAS  Google Scholar 

  • Gerli, R., Bistoni, O., Russano, A., Fiorucci, S., Borgato, L., Cesarotti, M. E., and Lunardi, C., In vivo activated T cells in rheumatoid synovitis. Analysis of Th1- and Th2-type cytokine production at clonal level in different stages of disease. Clin. Exp. Immunol., 129, 549–555 (2002).

    Article  PubMed  CAS  Google Scholar 

  • Guendez, R., Kallithraka, S., Makris, D. P., and Kefalas, P., An analytical survey of the polyphenols of seeds of varieties of grape (Vitis vinifera) cultivated in Greece: implications for exploitation as a source of value-added phytochemicals. Phytochem. Anal., 16, 17–23 (2005).

    Article  PubMed  CAS  Google Scholar 

  • Han, Y. and Cutler, J. E., Antibody response that protects against disseminated candidiasis. Infect. Immunl., 63, 2714–2719 (1995).

    CAS  Google Scholar 

  • Han, Y., Morrison, R. P., and Cutler, J. E., A vaccine and monoclonal antibodies that enhance mouse resistance to Candida albicans vaginal infection. Infect. Immun., 66, 5771–5776 (1998).

    PubMed  CAS  Google Scholar 

  • Han, Y., Kozel, T. R., Zhang, M. X., MacGill, R. S., Carroll, M. C., and Cutler, J. E., Complement is essential for protection by an IgM and an IgG3 monoclonal antibody against experimental, hematogenously disseminated candidiasis. J. Immunol., 167, 1550–1557 (2001).

    PubMed  CAS  Google Scholar 

  • Han, Y., Ginkgo terpene component has an anti-inflammatory effect on Candida albicans-caused arthritic inflammation. Int. Immunopharmacol., 5, 1049–1056 (2005).

    Article  PubMed  CAS  Google Scholar 

  • Han, Y., Rutin has therapeutic effect on septic arthritis caused by Candida albicans. Int. Immunopharmacol., 9, 207–211 (2009).

    Article  PubMed  CAS  Google Scholar 

  • Jayakrishna, G., Reddy, M. K., Jayaprakasam, B., Gunasekar, D., Blond, A., and Bodo, B., A new biflavonoid from Ochna beddomei. J. Asian Nat. Prod. Res., 5, 83–87 (2003).

    Article  PubMed  CAS  Google Scholar 

  • Jayaprakasam, B., Damu, A. G., Rao, K. V., Gunasekar, D., Blond, A., and Bodo, B., 7-O-Methyltetrahydroochnaflavone, a new biflavanone from Ochna beddomei. J. Nat. Prod., 63, 507–508 (2000).

    Article  PubMed  CAS  Google Scholar 

  • Kinne, R. W., Bräuer, R., Stuhlmüller, B., Palombo-Kinne, E., and Burmester, G. R., Macrophages in rheumatoid arthritis. Arthritis Res., 2, 189–202 (2000). Lee, J. H. and Han, Y., Ginsenoside Rg1 helps mice resist to disseminated candidiasis by Th1 type differentiation of CD4+ T cell. Int. Immunopharmacol., 6, 1424–1430 (2006).

    Article  PubMed  CAS  Google Scholar 

  • Lee, J. H., Lee, J. Y., Park, J. H., Jung, H. S., Kim, J. S., Kang, S. S., Kim, Y. S., and Han, Y., Immunoregulatory activity by daucosterol, a β-sitosterol glycoside, induces protective Th1 immune response against disseminated Candidiasis in mice. Vaccine, 25, 3834–3840 (2007).

    Article  PubMed  CAS  Google Scholar 

  • Lee, J. H., Park, J. H., Kim, Y. S., and Han, Y., Chlorogenic acid, a polyphenolic compound, treats mice with septic arthritis caused by Candida albicans. Int. Immunopharmacol., 8, 1681–1685 (2008).

    Article  PubMed  CAS  Google Scholar 

  • Lee, J. Y., Lee, J. H., Park, J. H., Kim, S. Y., Choi, J. Y., Lee, S. H., Kim, Y. S., Kang, S. S., Jang, E. C., and Han, Y., Liquiritigenin, a licorice flavonoid, helps mice resist disseminated candidiasis due to Candida albicans by Th1 immune response, whereas liquiritin, its glycoside form, does not. Int. Immunopharmacol., 9, 632–638 (2009).

    Article  PubMed  CAS  Google Scholar 

  • Lee, S. J., Choi, J. H., Son, K. H., Chang, H. W., Kang, S. S., and Kim, H. P., Suppression of mouse lymphocyte proliferation in vitro by naturally-occurring biflavonoids. Life Sci., 57, 551–558 (1995).

    Article  PubMed  CAS  Google Scholar 

  • Lotito, A. P., Muscará, M. N., Kiss, M. H., Teixeira, S. A., Novaes, G. S., Laurindo, I. M., Silva, C. A., and Mello, S. B., Nitric oxide-derived species in synovial fluid from patients with juvenile idiopathic arthritis. J. Rheumatol., 31, 992–997 (2004).

    PubMed  CAS  Google Scholar 

  • Mosmann, T. R. and Coffman, R. L., TH1 and TH2 cells: different patterns of lymphokine secretion lead to different functional properties. Annu. Rev. Immunol., 7, 145–173 (1989).

    Article  PubMed  CAS  Google Scholar 

  • Munder, M., Mallo, M., Eichmann, K., and Modolell, M., Murine macrophages secrete interferon γ upon combined stimulation with interleukin (IL)-12 and IL-18: A novel pathway of autocrine macrophage activation. J. Exp. Med., 187, 2103–2108 (1998).

    Article  PubMed  CAS  Google Scholar 

  • Nissler, K., Pohlers, D., Hückel, M., Simon, J., Bräuer, R., and Kinne, R. W., Anti-CD4 monoclonal antibody treatment in acute and early chronic antigen induced arthritis: influence on macrophage activation. Ann. Rheum. Dis., 63, 1470–1477 (2004).

    Article  PubMed  CAS  Google Scholar 

  • Ogmundsdóttir, H. M. and Weir, D. M., Mechanisms of macrophage activation. Clin. Exp. Immunol., 40, 223–234 (Review) (1980).

    PubMed  Google Scholar 

  • Panayi, G. S., Lanchbury, J. S., and Kingsley, G. H., The importance of the T cell in initiating and maintaining the chronic synovitis of rheumatoid arthritis. Arthritis Rheum., 35, 729–735 (1992).

    Article  PubMed  CAS  Google Scholar 

  • Reutrakul, V., Ningnuek, N., Pohmakotr, M., Yoosook, C., Napaswad, C., Kasisit, J., Santisuk, T., and Tuchinda, P., Anti HIV-1 flavonoid glycosides from Ochna integerrima. Planta Med., 73, 683–688 (2007).

    Article  PubMed  CAS  Google Scholar 

  • Schaberg, D. R., Culver, D. H., and Gaynes, R. P., Major trends in the microbial etiology of nosocomial infection. Am. J. Med., 16, 72S–75S (1991).

    Article  Google Scholar 

  • Son, K. H., Park, J. O., Chung, K. C., Chang, H. W., Kim, H. P., Kim, J. S., and Kang, S. S., Flavonoids from the aerial parts of Lonicera japonica. Arch. Pharm. Res., 15, 365–370 (1992).

    Article  CAS  Google Scholar 

  • Son, M. J., Moon, T. C., Lee, E. K., Son, K. H., Kim, H. P., Kang, S. S., Son, J. K., Lee, S. H., and Chang, H. W., Naturally occurring biflavonoid, ochnaflavone, inhibits cyclooxygenases-2 and 5-lipooxygenase in mouse bone marrow-derived mast cells. Arch. Pharm. Res., 29, 282–286 (2006).

    Article  PubMed  CAS  Google Scholar 

  • Suh, S. J., Chung, T. W., Son, M. J., Kim, S. H., Moon, T. C., Son, K. H., Kim, H. P., Chang, H. W., and Kim, C. H., The naturally occurring biflavonoid, ochnaflavone, inhibits LPS-induced iNOS expression, which is mediated by ERK1/2 via NF-κB regulation, in RAW 264.7 cells. Arch. Biochem. Biophys., 447, 136–146 (2006).

    Article  PubMed  CAS  Google Scholar 

  • Van den Broek, M. F., Van de Langerijt, L. G. M., Van Bruggen, M. C. J., Billingham, M. E. J., and Van den Berg, W. B., Treatment of rats with monoclonal anti-CD4 induces long-term resistance to streptococcal cell wallinduced arthritis. Eur. J. Immunol., 22, 57–61 (1992).

    Article  PubMed  Google Scholar 

  • Zafirova, Y., Yordanov, M., and Kalfin, R., Antiarthritic effect of VIP in relation to the host resistance against Candida albicans infection. Int. Immunol., 16, 1125–1131 (2004).

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. School of Korean Medicine, Pusan National University, Yangsan, 626-870, Korea

    Jue-Hee Lee

Authors
  1. Jue-Hee Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jue-Hee Lee.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Lee, JH. Involvement of T-cell immunoregulation by ochnaflavone in therapeutic effect on fungal arthritis due to Candida albicans . Arch. Pharm. Res. 34, 1209–1217 (2011). https://doi.org/10.1007/s12272-011-0720-0

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12272-011-0720-0

Key words

Search

Navigation