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Different Curcuminoids Inhibit T-Lymphocyte Proliferation Independently of Their Radical Scavenging Activities

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Abstract

Purpose

We investigated the inhibitory effects of curcumin, curcumin derivatives and degradation products on OKT3-induced human peripheral blood mononuclear cell (PBMC) proliferation and the role of their radical scavenging activity.

Methods

OKT3-induced human PBMC proliferation was determined by measuring 3H-thymidine incorporation. Radical scavenging activity was evaluated by using an in vitro DPPH assay.

Results

OKT3-induced PBMC proliferation was inhibited by curcumin, isocurcumin, bisdesmethoxy-, diacetyl-, tetrahydro-, hexahydro-, and octahydrocurcumin as well as by vanillin, ferulic acid, and dihydroferulic acid with IC50-values of 2.8, 2.8, 6.4, 1.0, 25, 38, 82, 729, 457, and >1,000 μM, respectively. The investigated substances with the strongest effect on radical scavenging were tetrahydro-, hexahydro-, and octahydrocurcumin with IC50 values of 10.0, 11.7, and 12.3 μM, respectively. IC50-values of dihydroferulic acid, ferulic acid, and curcumin were 19.5, 37, and 40 μM. The substances with the lowest radical scavenging activities were vanillin, isocurcumin, diacetylcurcumin, and bisdesmethoxycurcumin with IC50 values higher than 100 μM each.

Conclusions

Curcuminoid-induced inhibition of OKT3-induced PBMC proliferation depends on the number of carbon atoms and double bonds of the 1,6-heptadiene-3,5-dione structure as well as on the phenolic ring substitutes of the curcuminoids but is not correlated to their respective radical scavenging activity.

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Abbreviations

ABTS:

2,2-azino-bis(3-ethylbenzthiazoline-6-sulphonic acid)

DPPH:

1,1-diphenyl-2-picrylhydrazyl radical

HBC:

2-hydroxypropyl-γ-cyclodextrin

HHC:

hexahydrocurcumin

IC50 :

halfmaximal inhibitory concentration

JNK:

junN-terminal kinase

NFκB:

nuclear factor κB

OHC:

octahydrocurcumin

OKT3:

mouse anti-human CD3 antibody

PBMC:

peripheral blood mononuclear cells

THC:

tetrahydrocurcumin

References

  1. M. Lechtenberg, B. Quandt, and A. Nahrstedt. Quantitative determination of curcuminoids in Curcuma rhizomes and rapid differentiation of Cucurma domestica Val. and Curcuma xanthorrhiza Roxb. by capillary electrophoresis. Phytochem. Anal. 15:152–158 (2004).

    Article  PubMed  CAS  Google Scholar 

  2. B. B. Aggarwal, C. Sundaram, N. Malani, and H. Ichikawa. Curcumin: the Indian solid gold. Adv. Exp. Med. Biol. 595:1–75 (2007).

    Article  PubMed  Google Scholar 

  3. D. A. Dickinson, K. E. Iles, A. F. Wigley, and H. J. Forman. Analysis of transcription factor remodeling in phase II gene expression with Curcumin. Methods Enzymol. 378:302–318 (2004).

    Article  PubMed  CAS  Google Scholar 

  4. B. Joe, M. Vijaykumar, and B. R. Lokesh. Biological properties of Curcumin—cellular and molecular mechanisms of action. Crit. Rev. Food Sci. Nutr. 44:97–111 (2004).

    Article  PubMed  CAS  Google Scholar 

  5. R. K. Maheshwari, A. K. Singh, J. Gaddipati, and R. C. Srimal. Multiple biological activities of curcumin: A short review. Life Sci. 78:2081–2087 (2006).

    Article  PubMed  CAS  Google Scholar 

  6. W. F. Chen, S. L. Deng, B. Zhou, L. Yang, and Z. L. Liu. Curcumin and its analogues as potent inhibitors of low density lipoprotein oxidation. H-atom abstraction from the phenolic groups and possible involvement of the 4-hydroxy-3-methoxyphenyl groups. Free Radic. Biol. Med. 40:526–535 (2006).

    Article  PubMed  CAS  Google Scholar 

  7. X. Gao, J. Kuo, H. Jiang, D. Deeb, Y. Liu, G. Divine, R. A. Chapman, S. A. Dulchavsky, and S. C. Gautam. Immunmodulatory activity of Curcumin: suppression of lymphocyte proliferation, development of cellmediated cytotoxicity, and cytokine production in vitro. Biochem. Pharmacol. 68:51–61 (2004).

    Article  PubMed  CAS  Google Scholar 

  8. D. Ranjan, T. D. Johnston, G. Wu, L. Elliot, S. Bondada, and M. Nagabhushan. Curcumin blocks cyclosporine A-resistant CD28 costimulatory pathway of human T-cell proliferation. J. Surg. Res. 77:174–178 (1998).

    Article  PubMed  CAS  Google Scholar 

  9. Y. J. Wang, M. H. Pan, A. L. Cheng, L. I. Lin, Y. S. Ho, C. Y. Hsieh, and J. K. Lin. Stability of curcumin in buffer solutions and characterization of its degradation products. J. Pharm. Biomed. Anal. 15:1867–1876 (1997).

    Article  PubMed  CAS  Google Scholar 

  10. M. H. Pan, T. M. Huang, and J. K. Lin. Biotransformation of curcumin through reduction and glucuronidation in mice. Drug Metabol. Dispos. 27:486–494 (1999).

    CAS  Google Scholar 

  11. P. J. Roughley, and D. A. Whiting. Experiments in the biosynthesis of curcumin. J. Chem. Soc. 20:2379–2388 (1973).

    Google Scholar 

  12. K. Endo, E. Kanno, and Y. Oshima. Structures of antifungal diarylheptenones, gingerenones A, B, C and isogingerenone B, isolated from the rhizomes of Zingiber officinale. Phytochemistry. 29:797–799 (1990).

    Article  CAS  Google Scholar 

  13. S. I. Y. Uehara, K. Akiyama, H. Morita, K. Takeya, and H. Itokawa. Diaryheptanoids from the rhizomes of Curcuma xanthorrhiza and Alpinia officinarium. Chem. Pharm. Bull. 35:3298–3304 (1987).

    CAS  Google Scholar 

  14. M. T. Huang, W. Ma, Y. P. Lu, R. L. Chang, C. Fisher, P. S. Manchand, H. L. Newmark, and A. H. Conney. Effects of curcumin demethoxycurcumin, bisdemethoxycurcumin and tetrahydrocurcumin on 12-O-tetradecanoylphorbol-13-acetate-induced tumor promotion. Carcinogenesis. 16:2493–2497 (1995).

    Article  PubMed  CAS  Google Scholar 

  15. B. Vieregge, K. Resch, and V. Kaever. Synergistic effects of the alkaloid sinomenine in combination with the immunosuppressive drugs tacrolimus and mycophenolic acid. Planta Med. 65:80–82 (1999).

    Article  PubMed  CAS  Google Scholar 

  16. P. Venkatesan, and M. N. A. Rao. Structure–activity relationships for the inhibition of lipid peroxidation and the scavenging of free radicals by synthetic symmetrical curcumin analogues. J. Pharm. Pharmacol. 52:1123–1128 (2000).

    Article  PubMed  CAS  Google Scholar 

  17. P. Somparn, C. Phisalaphong, S. Nakornchai, S. Unchern, and N. P. Morales. Comparative antioxidant activities of curcumin and its demethoxy and hydrogenated derivatives. Biol. Pharm. Bull. 30:74–78 (2007).

    Article  PubMed  CAS  Google Scholar 

  18. J. N. Commandeur, and N. P. Vermeulen. Cytotoxicity and cytoprotective activities of natural compounds. The case of curcumin. Xenobiotica. 26:667–680 (1996).

    Article  PubMed  CAS  Google Scholar 

  19. Y. Sugiyama, S. Kawakishi, and T. Osawa. Involvement of the beta-diketone moiety in the antioxidative mechanism of tetrahydrocurcumin. Biochem. Pharmacol. 52:519–525 (1996).

    Article  PubMed  CAS  Google Scholar 

  20. K. I. Priyadarsini, D. K. Maity, G. H. Naik, M. S. Kumar, M. K. Unnikrishnan, J. G. Satav, and H. Mohan. Role of phenolic O–H and methylene hydrogen on the free radical reactions and antioxidant activity of curcumin. Free Radic. Biol. Med. 35:475–484 (2003).

    Article  PubMed  CAS  Google Scholar 

  21. S. Venkateswarlu, M. S. Ramachandra, and G. V. Subbaraju. Synthesis and biological evaluation of polyhydroxycurcuminoids. Bioorg. Med. Chem. 23:6374–6380 (2005).

    Article  CAS  Google Scholar 

  22. V. P. Menon, and A. R. Sudheer. Antioxidant and anti-inflammatory properties of curcumin. Adv. Exp. Med. Biol. 595:105–125 (2007).

    Article  PubMed  Google Scholar 

  23. N. Sreejayan, and M. N. Rao. Free radical scavenging activities of curcuminoids. Arzneimittelforschung. 46:169–171 (1996).

    PubMed  CAS  Google Scholar 

  24. Y. R. Chen, and T. H. Tan. Inhibition of the c-Jun N-terminal kinase (JNK) signaling pathway by curcumin. Oncogene. 17:173–178 (1998).

    Article  PubMed  CAS  Google Scholar 

  25. S. Singh, and B. B. Aggarwal. Activation of transcription factor NF-kappa B is suppressed by curcumin (diferuloylmethane). J. Biol. Chem. 270:24995–24500 (1995).

    Article  PubMed  CAS  Google Scholar 

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Acknowledgements

We thank Annette Garbe for excellent technical assistance. This study was supported by the Deutsche Forschungsgemeinschaft grant SFB265 A7.

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Authors and Affiliations

  1. Institute of Pharmacology, Hannover Medical School, 30623, Hannover, Germany

    Michael Deters, Heiko Knochenwefel, Daniel Lindhorst, Therese Koal, Klaus Resch & Volkhard Kaever

  2. Institute of Organic Chemistry, Leibnitz Universität Hannover, 30167, Hannover, Germany

    Hartmut H. Meyer

  3. Pharmaceutical Chemistry, Christian-Albrecht’s-University Kiel, 24118, Kiel, Germany

    Wolfram Hänsel

Authors
  1. Michael Deters
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  2. Heiko Knochenwefel
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  3. Daniel Lindhorst
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  4. Therese Koal
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  6. Wolfram Hänsel
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  7. Klaus Resch
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  8. Volkhard Kaever
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Corresponding author

Correspondence to Volkhard Kaever.

Additional information

This work was part of HK’s thesis at the Hannover Medical School.

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Deters, M., Knochenwefel, H., Lindhorst, D. et al. Different Curcuminoids Inhibit T-Lymphocyte Proliferation Independently of Their Radical Scavenging Activities. Pharm Res 25, 1822–1827 (2008). https://doi.org/10.1007/s11095-008-9579-2

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  • DOI: https://doi.org/10.1007/s11095-008-9579-2

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