Skip to main content

Curcumin improves treatment outcome of Takayasu arteritis patients by reducing TNF-α: a randomized placebo-controlled double-blind clinical trial

Abstract

Tumor necrosis factor (TNF) inhibitors have been found to exhibit certain efficacy in treating refractory Takayasu arteritis (TA) in clinic despite severe adverse effects. The aim of this study is to investigate a natural anti-TNF compound, curcumin, its function, and its potential as treatment against TA. In total, 246 patients who were diagnosed of acute TA participated have completed this clinical trial. They were randomly assigned in either treatment group or control group, in which they were daily administered with curcumin or placebo accordingly for 4 weeks with weekly revisits for data collection. The treatment outcome consisted of a primary one defined using Birmingham Vascular Activity Score (BVAS) and a secondary one defined by laboratory results, e.g., C-reactive protein (CRP), TNF-α, and erythrocyte sedimentation rate (ESR). In this study, the primary and secondary treatment outcomes were found to be steadily attenuated in patients who received curcumin treatment, while showed no significant change in patients in placebo group. TNF-α was found to be significantly correlated with BVAS scores (γ 2 = 0.81, p = 0.016), ESR (γ 2 = 0.76, p = 0.037), and plasma levels of CRP (γ 2 = 0.79, p = 0.041). The treatment outcome was greatly improved by curcumin administration probably due to its anti-TNF property.

This is a preview of subscription content, access via your institution.

Fig. 1
Fig. 2
Fig. 3

References

  1. 1.

    Ishihara T, Haraguchi G, Tezuka D, Kamiishi T, Inagaki H, Isobe M. Diagnosis and assessment of Takayasu arteritis by multiple biomarkers. Circ J. 2013;77:477–83.

    CAS  Article  PubMed  Google Scholar 

  2. 2.

    Kallappa Parameshwarappa S, Mandjiny N, Kavumkal Rajagopalan B, Radhakrishnan N, Samavedam S, Unnikrishnan M. Intact giant abdominal aortic aneurysm due to Takayasu arteritis. Ann Vasc Surg. 2013;27:671 e11–4. doi:10.1016/j.avsg.2012.06.022.

    Article  Google Scholar 

  3. 3.

    Schmidt J, Kermani TA, Bacani AK, Crowson CS, Matteson EL, Warrington KJ. Tumor necrosis factor inhibitors in patients with Takayasu arteritis: experience from a referral center with long-term followup. Arthritis Care Res (Hoboken). 2012;64:1079–83. doi:10.1002/acr.21636.

    PubMed  Google Scholar 

  4. 4.

    Nasu T. Takayasu’s truncoarteritis in Japan. A statistical observation of 76 autopsy cases. Pathol Microbiol (Basel). 1975;43:140–6.

    CAS  Google Scholar 

  5. 5.

    Maksimowicz-McKinnon K, Clark TM, Hoffman GS. Limitations of therapy and a guarded prognosis in an American cohort of Takayasu arteritis patients. Arthritis Rheum. 2007;56:1000–9. doi:10.1002/art.22404.

    Article  PubMed  Google Scholar 

  6. 6.

    Maksimowicz-McKinnon K, Hoffman GS. Takayasu arteritis: what is the long-term prognosis? Rheum Dis Clin N Am. 2007;33:777–86. vi doi:10.1016/j.rdc.2007.07.014.

    Article  Google Scholar 

  7. 7.

    Wallis RS, Ehlers S. Tumor necrosis factor and granuloma biology: explaining the differential infection risk of etanercept and infliximab. Semin Arthritis Rheum. 2005;34:34–8. doi:10.1016/j.semarthrit.2005.01.009.

    CAS  Article  PubMed  Google Scholar 

  8. 8.

    Hoffman GS, Merkel PA, Brasington RD, Lenschow DJ, Liang P. Anti-tumor necrosis factor therapy in patients with difficult to treat Takayasu arteritis. Arthritis Rheum. 2004;50:2296–304. doi:10.1002/art.20300.

    CAS  Article  PubMed  Google Scholar 

  9. 9.

    Tato F, Rieger J, Hoffmann U. Refractory Takayasu’s arteritis successfully treated with the human, monoclonal anti-tumor necrosis factor antibody adalimumab. Int Angiol. 2005;24:304–7.

    CAS  PubMed  Google Scholar 

  10. 10.

    Tanaka F, Kawakami A, Iwanaga N, Tamai M, Izumi Y, Aratake K, et al. Infliximab is effective for Takayasu arteritis refractory to glucocorticoid and methotrexate. Intern Med. 2006;45:313–6.

    Article  PubMed  Google Scholar 

  11. 11.

    Molloy ES, Langford CA, Clark TM, Gota CE, Hoffman GS. Anti-tumour necrosis factor therapy in patients with refractory Takayasu arteritis: long-term follow-up. Ann Rheum Dis. 2008;67:1567–9. doi:10.1136/ard.2008.093260.

    CAS  Article  PubMed  Google Scholar 

  12. 12.

    Maffei S, Di Renzo M, Santoro S, Puccetti L, Pasqui AL. Refractory Takayasu arteritis successfully treated with infliximab. Eur Rev Med Pharmacol Sci. 2009;13:63–5.

    CAS  PubMed  Google Scholar 

  13. 13.

    Nunes G, Neves FS, Melo FM, de Castro GR, Zimmermann AF, Pereira IA. Takayasu arteritis: anti-TNF therapy in a Brazilian setting. Rev Bras Reumatol. 2010;50:291–8.

    Article  PubMed  Google Scholar 

  14. 14.

    Buonuomo PS, Bracaglia C, Campana A, Insalaco A, Pardeo M, Cortis E, et al. Infliximab therapy in pediatric Takayasu’s arteritis: report of two cases. Rheumatol Int. 2011;31:93–5. doi:10.1007/s00296-009-1147-5.

    Article  PubMed  Google Scholar 

  15. 15.

    Gupta SC, Tyagi AK, Deshmukh-Taskar P, Hinojosa M, Prasad S, Aggarwal BB. Downregulation of tumor necrosis factor and other proinflammatory biomarkers by polyphenols. Arch Biochem Biophys. 2014;559:91–9. doi:10.1016/j.abb.2014.06.006.

    CAS  Article  PubMed  Google Scholar 

  16. 16.

    Usharani P, Mateen AA, Naidu MU, Raju YS, Chandra N. Effect of NCB-02, atorvastatin and placebo on endothelial function, oxidative stress and inflammatory markers in patients with type 2 diabetes mellitus: a randomized, parallel-group, placebo-controlled, 8-week study. Drugs R D. 2008;9:243–50.

    CAS  Article  PubMed  Google Scholar 

  17. 17.

    Koosirirat C, Linpisarn S, Changsom D, Chawansuntati K, Wipasa J. Investigation of the anti-inflammatory effect of Curcuma longa in Helicobacter pylori-infected patients. Int Immunopharmacol. 2010;10:815–8. doi:10.1016/j.intimp.2010.04.021.

    CAS  Article  PubMed  Google Scholar 

  18. 18.

    He ZY, Shi CB, Wen H, Li FL, Wang BL, Wang J. Upregulation of p53 expression in patients with colorectal cancer by administration of curcumin. Cancer Investig. 2011;29:208–13. doi:10.3109/07357907.2010.550592.

    CAS  Article  Google Scholar 

  19. 19.

    Arend WP, Michel BA, Bloch DA, Hunder GG, Calabrese LH, Edworthy SM, et al. The American College of Rheumatology 1990 criteria for the classification of Takayasu arteritis. Arthritis Rheum. 1990;33:1129–34.

    CAS  Article  PubMed  Google Scholar 

  20. 20.

    Luqmani RA, Bacon PA, Moots RJ, Janssen BA, Pall A, Emery P, et al. Birmingham Vasculitis Activity Score (BVAS) in systemic necrotizing vasculitis. QJM. 1994;87:671–8.

    CAS  PubMed  Google Scholar 

  21. 21.

    Nooshin D, Neda P, Shahdokht S, Ali J. Ten-year investigation of clinical, laboratory and radiologic manifestations and complications in patients with Takayasu’s arteritis in three university hospitals. Malays J Med Sci. 2013;20:44–50.

    PubMed  PubMed Central  Google Scholar 

  22. 22.

    Minciullo PL, Catalano A, Mandraffino G, Casciaro M, Crucitti A, Maltese G, et al. Inflammaging and anti-inflammaging: the role of cytokines in extreme longevity. Arch Immunol Ther Exp. 2016;64:111–26. doi:10.1007/s00005-015-0377-3.

    CAS  Article  Google Scholar 

  23. 23.

    Neves H, Kwok HF. Recent advances in the field of anti-cancer immunotherapy. BBA Clin. 2015;3:280–8. doi:10.1016/j.bbacli.2015.04.001.

    Article  PubMed  PubMed Central  Google Scholar 

  24. 24.

    Cheng X, Wang Q, Li N, Zhao H. Effects of resveratrol on hippocampal astrocytes and expression of TNF-alpha in Alzheimer’s disease model rate. Wei Sheng Yan Jiu. 2015;44:610–4.

    CAS  PubMed  Google Scholar 

  25. 25.

    Park MC, Lee SW, Park YB, Lee SK. Serum cytokine profiles and their correlations with disease activity in Takayasu’s arteritis. Rheumatology (Oxford). 2006;45:545–8. doi:10.1093/rheumatology/kei266.

    CAS  Article  PubMed  Google Scholar 

  26. 26.

    Tripathy NK, Gupta PC, Nityanand S. High TNF-alpha and low IL-2 producing T cells characterize active disease in Takayasu’s arteritis. Clin Immunol. 2006;118:154–8. doi:10.1016/j.clim.2005.09.010.

    CAS  Article  PubMed  Google Scholar 

  27. 27.

    Comarmond C, Plaisier E, Dahan K, Mirault T, Emmerich J, Amoura Z, et al. Anti TNF-alpha in refractory Takayasu’s arteritis: cases series and review of the literature. Autoimmun Rev. 2012;11:678–84. doi:10.1016/j.autrev.2011.11.025.

    CAS  Article  PubMed  Google Scholar 

  28. 28.

    Quartuccio L, Schiavon F, Zuliani F, Carraro V, Catarsi E, Tavoni AG, et al. Long-term efficacy and improvement of health-related quality of life in patients with Takayasu’s arteritis treated with infliximab. Clin Exp Rheumatol. 2012;30:922–8.

    PubMed  Google Scholar 

  29. 29.

    Singh S, Aggarwal BB. Activation of transcription factor NF-kappa B is suppressed by curcumin (diferuloylmethane) [corrected]. J Biol Chem. 1995;270:24995–5000.

    CAS  Article  PubMed  Google Scholar 

  30. 30.

    Abe Y, Hashimoto S, Horie T. Curcumin inhibition of inflammatory cytokine production by human peripheral blood monocytes and alveolar macrophages. Pharmacol Res. 1999;39:41–7. doi:10.1006/phrs.1998.0404.

    CAS  Article  PubMed  Google Scholar 

  31. 31.

    Jang MK, Sohn DH, Ryu JH. A curcuminoid and sesquiterpenes as inhibitors of macrophage TNF-alpha release from Curcuma zedoaria. Planta Med. 2001;67:550–2. doi:10.1055/s-2001-16482.

    CAS  Article  PubMed  Google Scholar 

  32. 32.

    Gao X, Kuo J, Jiang H, Deeb D, Liu Y, Divine G, et al. Immunomodulatory activity of curcumin: suppression of lymphocyte proliferation, development of cell-mediated cytotoxicity, and cytokine production in vitro. Biochem Pharmacol. 2004;68:51–61. doi:10.1016/j.bcp.2004.03.015.

    CAS  Article  PubMed  Google Scholar 

  33. 33.

    Jin CY, Lee JD, Park C, Choi YH, Kim GY. Curcumin attenuates the release of pro-inflammatory cytokines in lipopolysaccharide-stimulated BV2 microglia. Acta Pharmacol Sin. 2007;28:1645–51. doi:10.1111/j.1745-7254.2007.00651.x.

    CAS  Article  PubMed  Google Scholar 

  34. 34.

    Woo HM, Kang JH, Kawada T, Yoo H, Sung MK, Yu R. Active spice-derived components can inhibit inflammatory responses of adipose tissue in obesity by suppressing inflammatory actions of macrophages and release of monocyte chemoattractant protein-1 from adipocytes. Life Sci. 2007;80:926–31. doi:10.1016/j.lfs.2006.11.030.

    CAS  Article  PubMed  Google Scholar 

  35. 35.

    Cretu E, Trifan A, Vasincu A, Miron A. Plant-derived anticancer agents—curcumin in cancer prevention and treatment. Rev Med Chir Soc Med Nat Iasi. 2012;116:1223–9.

    PubMed  Google Scholar 

  36. 36.

    Nanji AA, Jokelainen K, Tipoe GL, Rahemtulla A, Thomas P, Dannenberg AJ. Curcumin prevents alcohol-induced liver disease in rats by inhibiting the expression of NF-kappa B-dependent genes. Am J Physiol Gastrointest Liver Physiol. 2003;284:G321–7. doi:10.1152/ajpgi.00230.2002.

    CAS  Article  PubMed  Google Scholar 

  37. 37.

    El-Moselhy MA, Taye A, Sharkawi SS, El-Sisi SF, Ahmed AF. The antihyperglycemic effect of curcumin in high fat diet fed rats. Role of TNF-alpha and free fatty acids. Food Chem Toxicol. 2011;49:1129–40. doi:10.1016/j.fct.2011.02.004.

    CAS  Article  PubMed  Google Scholar 

  38. 38.

    Siddiqui AM, Cui X, Wu R, Dong W, Zhou M, Hu M, et al. The anti-inflammatory effect of curcumin in an experimental model of sepsis is mediated by up-regulation of peroxisome proliferator-activated receptor-gamma. Crit Care Med. 2006;34:1874–82. doi:10.1097/01.CCM.0000221921.71300.BF.

    CAS  Article  PubMed  Google Scholar 

  39. 39.

    Leyon PV, Kuttan G. Studies on the role of some synthetic curcuminoid derivatives in the inhibition of tumour specific angiogenesis. J Exp Clin Cancer Res. 2003;22:77–83.

    CAS  PubMed  Google Scholar 

  40. 40.

    Nishida M, Nishiumi S, Mizushina Y, Fujishima Y, Yamamoto K, Masuda A, et al. Monoacetylcurcumin strongly regulates inflammatory responses through inhibition of NF-kappaB activation. Int J Mol Med. 2010;25:761–7.

    CAS  PubMed  Google Scholar 

  41. 41.

    Huang WT, Niu KC, Chang CK, Lin MT, Chang CP. Curcumin inhibits the increase of glutamate, hydroxyl radicals and PGE2 in the hypothalamus and reduces fever during LPS-induced systemic inflammation in rabbits. Eur J Pharmacol. 2008;593:105–11. doi:10.1016/j.ejphar.2008.07.017.

    CAS  Article  PubMed  Google Scholar 

Download references

Author information

Affiliations

Authors

Corresponding author

Correspondence to Jingying Li.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Research involving human participants and/or animals

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Shao, N., Jia, H., Li, Y. et al. Curcumin improves treatment outcome of Takayasu arteritis patients by reducing TNF-α: a randomized placebo-controlled double-blind clinical trial. Immunol Res 65, 969–974 (2017). https://doi.org/10.1007/s12026-017-8917-z

Download citation

Keywords

  • Takayasu arteritis
  • Curcumin
  • Tumor necrosis factor
  • C-reactive protein
  • Birmingham Vascular Activity Score