Journal of Traditional Medical Complementary Therapies

.: REVIEW
Romatoid Artritte Tamamlayıcı ve Bütünleyici Tıp Uygulamalarının Dünü, Bugünü ve Yarını
Complementary and Alternative Medicine in Rheumatoid Arthritis: Yesterday, Today and Tomorrow
Mustafa İKİZEKa, Ceyhun NURİa, Nimet Emel LÜLECİb
aİntegratif Tıp Kliniği, Ankara, TÜRKİYE
bMarmara Üniversitesi, Halk Sağlığı ABD, İstanbul, TÜRKİYE
J Tradit Complem Med. 2020;3(2):224-45
doi: 10.5336/jtracom.2019-72570
Article Language: TR
Full Text
ÖZET
 Romatoid artrit [rheumatoid arthritis (RA)], en sık görülen otoimmün eklem hastalıklarından birisidir. Toplumun yaklaşık %0,5-1'ini etkileyen RA için mevcut hedefe yönelik tedavi protokolleri hastalık aktivitesini ölçer; konvansiyonel, steroid olmayan antiinflamatuar ilaçları [nonsteroidal anti-inflammatory drugs (NSAIDs)] ve metotreksat gibi biyolojik olmayan hastalık modifiye edici antiromatizmal ilaçları [disease-modifying antirheumatic drugs (DMARDs)] kullanır. Bununla birlikte tedavilerin bazılarına etkili şekilde yanıt vermeyen hastalar vardır ve verilen ilaçlar hastaları tatmin etmemektedir. Bu nedenle acilen yeni çözümlere ihtiyaç duyulduğu açıktır. Son zamanlarda tamamlayıcı ve alternatif tıp [complementary and alternative medicine(CAM)], RA tedavisinde son derece popülerdir. RA hastaları hayatlarında en az bir kez tamamlayıcı tedavilere başvurmuştur. CAM, genellikle modern tedavilerin yerine geçmek yerine onlara ek ve destekleyici olarak kullanılır. Mevcut biyolojik ilaçların sınırlamaları ve yan etkileri yüzünden, RA'lı birçok kişinin yüzünü CAM'a çevirmesi şaşırtıcı değildir. Aslında, bitkisel ilaçlar, diyet müdahalesi, manuel terapi, kalori kısıtlaması ve epigenomik yaklaşımlar kas-iskelet ağrısını azaltmada ümit vadetmektedir. Bu çalışmamız, RA tedavisinde CAM hakkında bilinenlere kısa bir genel bakış sağlar ve ayrıca yeşil çay, Tripterygium wilfordii, Curcuma longa, Veratrum grandiflorum ve Camellia sinensis gibi bitkilerin farmakolojik etkileri hakkında son bilgileri özetlemektedir. Bu derleme, ayrıca mikrobiyom, nütrigenomiks ve RA arasında bildirilen korelasyon ve altta yatan moleküler mekanizmaları da özetlemektedir. CAM tedavilerinin etkili olabileceği mekanizmaların derinlemesine anlaşılması ve netleştirilmesi RA semptomlarının azaltılmasında yeni moleküler ve besinsel hedeflerin keşfine yol açabilir ve RA hastaları için yeni tedavi olanakları sağlayabilir. Bunun sayesinde CAM ve konvansiyonel ilaç uygulamaların RA tedavisinde entegrasyonuna yardımcı olunabilir. Sonuç olarak burada, bazı rasyonel CAM modalitelerinin, RA tedavisindeki potansiyel rolünü incelemeyi amaçladık.

Anahtar Kelimeler: Geleneksel ve tamamlayıcı tıp; romatoid artrit
ABSTRACT
 Rheumatoid arthritis (RA) is one of the most prevalent autoimmune inflammatory joint diseases. RA affecting approximately 0.5-1.0% of the population. Current treatment-to-target strategy for RA measure disease activity scores and use conventional, nonsteroidal anti-inflammatory drugs (NSAIDs), and non-biological disease-modifying antirheumatic drugs (DMARDs) as methotrexate. Hovewer, there is a significant proportion of patients who do not respond efficiently to some of these therapies which has been far from patient satisfaction. Therefore, it is apparent that novel remedies are urgently needed. Recently, complementary and alternative medicine (CAM) is extremely popular worldwide for the alleviation of RA. Many RA patients frequently seek CAM at once in her/his life. CAM is usually used in addition to, and not as a substitute for conventional therapies. Given the poor effect of current drugs and the side effects, it is not at all surprising that many individuals with RA turn their face to CAM. Herbal medicines, dietary intervention, manuel therapy, calori restriction and epigenomic approach are promising in reducing musculoskeletal pain. This study provides a brief overview of what is known about CAM as a treatment for RA and will also summarize recent data for pharmacological effects of herbs including green tea, Tripterygium wilfordii, Curcuma longa, Veratrum grandiflorum and Camellia sinensis. Here we also summarise reported correlation and underlying molecular mechanisms among microbiome, nutriogenomics and RA. Deep understanding and clarification of the subtle mechanisms by which CAM therapies may be efficacious can be lead to discovering new molecular and nutritional targets in the relieving symptoms and provide new treatment opportunities for RA patients. This may assist the integration of CAM and conventional practices in the treatment of RA. Collectively, we aimed here to examine the potential role of some rationale CAM modalities in RA therapy.

Keywords: Traditional and complementary medicine; rheumatoid arthritis
REFERENCES:
  1. Deng G, Cassileth B. Complementary or alternative medicine in cancer care-myths and realities. Nat Rev Clin Oncol. 2013;10(11):656-64. [Crossref]  [PubMed] 
  2. Ernst E. How much of CAM is based on research evidence? Evid Based Complement Alternat Med. 2011;2011:676490. [Crossref]  [PubMed]  [PMC] 
  3. Hyndman IJ. Rheumatoid arthritis: past, present and future approaches to treating the disease. Int J Rheum Dis. 2017;20(4):417-19. [Crossref]  [PubMed] 
  4. Chen W, Li EC, Zheng WR. Policies on Chinese medicine in China may have enlightenments to complementary and alternative medicine in the world. Chin J Integr Med. 2018;24(10):789-93. [Crossref]  [PubMed] 
  5. Efferth T, Zacchino S, Georgiev MI, Liu L, Wagner H, Panossian A. Nobel Prize for artemisinin brings phytotherapy into the spotlight. Phytomedicine. 2015;22(13):A1-3. [Crossref]  [PubMed] 
  6. Astin JA. Why patients use alternative medicine: results of a national study. JAMA. 1998;279(19):1548-53. [Crossref]  [PubMed] 
  7. Smolen JS, Aletaha D, Barton A, Burmester GR, Emery P, Firestein GS, et al. Rheumatoid arthritis. Nat Rev Dis Primers. 2018;4:18001. [Crossref]  [PubMed] 
  8. Smolen JS, Aletaha D, McInnes IB. Rheumatoid arthritis. Lancet. 2016;388(10055):2023-38. [Crossref]  [PubMed] 
  9. Viatte S, Barton A. Genetics of rheumatoid arthritis susceptibility, severity, and treatment response. Semin Immunopathol. 2017;39(4):395-408. [Crossref]  [PubMed]  [PMC] 
  10. Lambert NC. Nonendocrine mechanisms of sex bias in rheumatic diseases. Nat Rev Rheumatol. 2019;15(11):673-86. [Crossref]  [PubMed] 
  11. Okada Y, Wu D, Trynka G, Raj T, Terao C, Ikari K, et al. Genetics of rheumatoid arthritis contributes to biology and drug discovery. Nature. 2014;506(7488):376-81. [PubMed] 
  12. Tuncer T, Gilgil E, Kaçar C, Kurtaiş Y, Kutlay Ş, Bütün B, et al. Prevalence of rheumatoid arthritis and spondyloarthritis in Turkey: a nationwide study. Arch Rheumatol. 2017;33(2):128-36. [Crossref]  [PubMed]  [PMC] 
  13. Balkrishna A, Sakat SS, Joshi K, Paudel S, Joshi D, Joshi K, et al. Herbo-mineral formulation 'Ashwashila' attenuates rheumatoid arthritis symptoms in collagen-antibody-induced arthritis (CAIA) mice model. Sci Rep. 2019;9(1):8025. [Crossref]  [PubMed]  [PMC] 
  14. Zhang Y, Dennis JA, Bishop FL, Cramer H, Leach M, Lauche R, et al. Complementary and alternative medicine use by U.S. adults with self-reported doctor-diagnosed arthritis: results from the 2012 National Health Interview Survey. PM R. 2019;11(10):1059-69. [Crossref]  [PubMed] 
  15. van Vollenhoven R. Treat-to-target in rheumatoid arthritis - are we there yet? Nat Rev Rheumatol. 2019;15(3):180-6. [Crossref]  [PubMed] 
  16. Falzer PR. Treat-to-target and shared decision making in rheumatoid arthritis treatment: is it feasible? Int J Rheum Dis. 2019;22(9):1706-13. [Crossref]  [PubMed] 
  17. Kalyoncu U, Ertenli Aİ, Kücükşahin O, Dalkılıç HE, Erden A, Bes C, et al. TReasure Çalışma Grubu. [Switching between biological DMARDs and associated reasons in rheumatoid arthritis and spondyloarthritis treatments: TReasure study-real life data]. J Turk Soc Rheumatol. 2019;11(1):1-9. [Crossref] 
  18. Alarcón GS. Epidemiology of rheumatoid arthritis. Rheum Dis Clin North Am. 1995;21(3):589-604. [PubMed] 
  19. Ernst E, Posadzki P. Complementary and alternative medicine for rheumatoid arthritis and osteoarthritis: an overview of systematic reviews. Curr Pain Headache Rep. 2011;15(6):431-7. [Crossref]  [PubMed] 
  20. Tamhane A, McGwin Jr G, Redden DT, Hughes LB, Brown EE, Westfall AO, et al. Complementary and alternative medicine use in African Americans with rheumatoid arthritis. Arthritis Care Res (Hoboken). 2014;66(2):180-9. [Crossref]  [PubMed]  [PMC] 
  21. Chen L, Michalsen A. Management of chronic pain using complementary and integrative medicine. BMJ. 2017;357:j1284. [Crossref]  [PubMed] 
  22. Nahin RL, Dahlhamer JM, Taylor BL, Barnes PM, Stussman BJ, Simile CM, et al. Health behaviors and risk factors in those who use complementary and alternative medicine. BMC Public Health. 2007;7:217. [Crossref]  [PubMed]  [PMC] 
  23. Tarner IH, Müller-Ladner U. Drug delivery systems for the treatment of rheumatoid arthritis. Expert Opin Drug Deliv. 2008;5(9):1027-37. [Crossref]  [PubMed] 
  24. Rao JK, Mihaliak K, Kroenke K, Bradley J, Tierney WM, Weinberger M. Use of complementary therapies for arthritis among patients of rheumatologists. Ann Intern Med. 1999;131(6):409-16. [Crossref]  [PubMed] 
  25. Orr DE, Bravo Gutiérrez GB, Fette D. From parallel to partnership. Leadersh Health Serv (Bradf Engl). 2019;32(4):493-508. [Crossref]  [PubMed] 
  26. Kjeldsen-Kragh J, Haugen M, Borchgrevink CF, Laerum E, Eek M, Mowinkel P, et al. Controlled trial of fasting and one-year vegetarian diet in rheumatoid arthritis. Lancet. 1991;338(8772):899-902. [Crossref]  [PubMed] 
  27. Müller H, Wilhelmi de Toledo F, Resch KL. A systematic review of clinical studies on fasting and vegetarian diets in the treatment of rheumatoid arthritis. Scand J Rheumatol. 2000;30:1-10.
  28. Fontana L, Partridge L, Longo VD. Extending healthy life span--from yeast to humans. Science. 2010;328(5976):321-6. [Crossref]  [PubMed]  [PMC] 
  29. Michalsen A, Li C. Fasting therapy for treating and preventing disease - current state of evidence. Forsch Komplementmed. 2013;20(6):444-53. [Crossref]  [PubMed] 
  30. Darlington LG, Ramsey NW, Mansfield JR. Placebo-controlled, blind study of dietary manipulation therapy in rheumatoid arthritis. Lancet. 1986;1(8475):236-8. [Crossref]  [PubMed] 
  31. Sköldstam L, Larsson L, Lindström FD. Effect of fasting and lactovegetarian diet on rheumatoid arthritis. Scand J Rheumatol. 1979;8(4):249-55. [Crossref]  [PubMed] 
  32. Udén AM, Trang L, Venizelos N, Palmblad J. Neutrophil functions and clinical performance after total fasting in patients with rheumatoid arthritis. Ann Rheum Dis. 1983;42(1):45-51. [Crossref]  [PubMed]  [PMC] 
  33. Hafström I, Ringertz B, Gyllenhammar H, Palmblad J, Harms-Ringdahl M. Effects of fasting on disease activity, neutrophil function, fatty acid composition, and leukotriene biosynthesis in patients with rheumatoid arthritis. Arthritis Rheum. 1988;31(5):585-92. [Crossref]  [PubMed] 
  34. Lindstrom TM, Robinson WH. Rheumatoid arthritis: a role for immunosenescence? J Am Geriatr Soc. 2010;58(8):1565-75. [Crossref]  [PubMed]  [PMC] 
  35. Häger J, Bang H, Hagen M, Frech M, Träger P, Sokolova MV, et al. The role of dietary fiber in rheumatoid arthritis patients: a feasibility study. Nutrients. 2019;11(10):2392. [Crossref]  [PubMed]  [PMC] 
  36. Ohsumi Y. Historical landmarks of autophagy research. Cell Res. 2014;24(1):9-23. [Crossref]  [PubMed]  [PMC] 
  37. Jaspers RT, Zillikens MC, Friesema ECH, delli Paoli G, Bloch W, Uitterlinden AG, et al. Exercise, fasting, and mimetics: toward beneficial combinations? FASEB J. 2017;31(1):14-28. [Crossref]  [PubMed] 
  38. Levine B, Kroemer G. biological functions of autophagy genes: a disease perspective. Cell. 2019;176(1-2):11-42. [Crossref]  [PubMed]  [PMC] 
  39. Leidal AM, Levine B, Debnath J. Autophagy and the cell biology of age-related disease. Nat Cell Biol. 2018;20(12):1338-48. [Crossref]  [PubMed] 
  40. Miyauchi T, Uchida Y, Kadono K, Hirao H, Kawasoe J, Watanabe T, et al. Up-regulation of FOXO1 and reduced inflammation by β-hydroxybutyric acid are essential diet restriction benefits against liver injury. PNAS. 2019;116(27):13533-42. [Crossref]  [PubMed]  [PMC] 
  41. Calabrese EJ, Blain R. The occurrence of hormetic dose responses in the toxicological literature, the hormesis database: an overview. Toxicol Appl Pharmacol. 2005;202(3):289-301. [Crossref]  [PubMed] 
  42. Isner JM, Sours HE, Paris AL, Ferrans VJ, Roberts WC: Sudden, unexpected death in avid dieters using the liquid-protein-modified-fast diet. Observations in 17 patients and the role of the prolonged QT interval. Circulation. 1979;60(6):1401-12. [Crossref]  [PubMed] 
  43. Spencer IO. Death during therapeutic starvation for obesity. Lancet. 1968;1(7555):1288-90. [Crossref]  [PubMed] 
  44. Frattali VP. Deaths associated with the liquid protein diet. Bull Natl Clgh Poison Control Cent. 1979;23(4):4-11. [PubMed] 
  45. Hearing SD. Refeeding syndrome. BMJ. 2004;328(7445):908-9. [Crossref]  [PubMed]  [PMC] 
  46. Cheng CW, Adams GB, Perin L, Wei M, Zhou X, Lam BS, et al. Prolonged fasting reduces IGF-1/PKA to promote hematopoietic-stem-cell-based regeneration and reverse immunosuppression. Cell Stem Cell. 2014;14(6):810-23. [Crossref]  [PubMed]  [PMC] 
  47. Askari A. The sodium pump and digitalis drugs: dogmas and fallacies. Pharmacol Res Perspect. 2019;7(4):e00505. [Crossref]  [PubMed]  [PMC] 
  48. DeSalvo JC, Skiba MB, Howe CL, Haiber KE, Funk JL. Natural product dietary supplement use by individuals with rheumatoid arthritis: a scoping review. Arthritis Care Res (Hoboken). 2019;71(6):787-97. [Crossref]  [PubMed]  [PMC] 
  49. Clarke TC, Black LI, Stussman BJ, Barnes PM, Nahin RL. Trends in the Use of Complementary Health Approaches Among Adults: United States, 2002-2012. Natl Health Stat Report. 2015;(79):1-16.
  50. Rose G. Why do patients with rheumatoid arthritis use complementary therapies? Musculoskeletal Care. 2006;4(2):101-15. [Crossref]  [PubMed] 
  51. Dudics S, Langan D, Meka RR, Venkatesha SH, Berman BM, Che CT, et al. Natural products for the treatment of autoimmune arthritis: their mechanisms of action, targeted delivery and interplay with the host microbiome. Int J Mol Sci. 2018;19(9):2508. [Crossref]  [PubMed]  [PMC] 
  52. Kuttan R, Bhanumathy P, Nirmala K, George MC. Potential anticancer activity of turmeric (Curcuma Longa). Cancer Lett. 1985;29(2):197-202. [Crossref]  [PubMed] 
  53. Haroyan A, Mukuchyan V, Mkrtchyan N, Minasyan N, Gasparyan S, Sargsyan A, et al. Efficacy and safety of curcumin and its combination with boswellic acid in osteoarthritis: a comparative, randomized, double-blind, placebo-controlled study. BMC Complement Altern Med. 2018;9;18(1):7. [Crossref]  [PubMed]  [PMC] 
  54. Nelson KM, Dahlin JL, Bisson J, Graham J, Pauli GF, Walters MA. The essential medicinal chemistry of curcumin. J Med Chem. 2017;60(5):1620-37. [Crossref]  [PubMed]  [PMC] 
  55. Zheng Z, Sun Y, Liu Z, Zhang M, Li C, Cai H. The effect of curcumin and its nanoformulation on adjuvant-induced arthritis in rats. Drug Des Devel Ther. 2015;9:4931-42. [Crossref]  [PubMed]  [PMC] 
  56. Kapoor B, Gupta R, Gupta M. Natural products in treatment of rheumatoid arthritis. Int J Green Pharm. 2017;11:S356-63.
  57. Daily JW, Yang M, Park S. Efficacy of turmeric extracts and curcumin for alleviating the symptoms of joint arthritis: a systematic review and meta-analysis of randomized clinical trials. J Med Food. 2016;19(8):717-29. [Crossref]  [PubMed]  [PMC] 
  58. Conigliaro P, Triggianese P, De Martino E, Fonti GL, Chimenti MS, Sunzini F, et al. Challenges in the treatment of rheumatoid arthritis. Autoimmun Rev. 2019;18(7):706-13. [Crossref]  [PubMed] 
  59. Javadi M, Khadem Haghighian H, Goodarzy S, Abbasi M, Nassiri-Asl M. Effect of curcumin nanomicelle on the clinical symptoms of patients with rheumatoid arthritis: a randomized, double-blind, controlled trial. Int J Rheum Dis. 2019;22(10):1857-62. [Crossref]  [PubMed] 
  60. Priyadarsini KI. Chemical and structural features influencing the biological activity of curcumin. Curr Pharm Des. 2013;19(11):2093-100. [Crossref]  [PubMed] 
  61. Concetta Scuto M, Mancuso C, Tomasello B, Laura Ontario M, Cavallaro A, Frasca F, et al. Curcumin, hormesis and the nervous system. Nutrients. 2019;11(10):2417. [Crossref]  [PubMed]  [PMC] 
  62. Calabrese V, Cornelius C, Dinkova-Kostova AT, Calabrese EJ, Mattson MP. Cellular stress responses, the hormesis paradigm, and vitagenes: novel targets for therapeutic intervention in neurodegenerative disorders. Antioxid Redox Signal. 2010;13(11):1763-811. [Crossref]  [PubMed]  [PMC] 
  63. Du L, Wang L, Wang B, Wang J, Hao M, Chen YB, et al. A novel compound AB38b attenuates oxidative stress and ECM protein accumulation in kidneys of diabetic mice through modulation of Keap1/Nrf2 signaling. Acta Pharmacol Sin. 2019;41(3):358-72. [Crossref]  [PubMed] 
  64. Rao YL, Ganaraja B, Joy T, Pai MM, Ullal SD, Murlimanju BV. Neuroprotective effects of resveratrol in Alzheimer's disease. Front Biosci (Elite Ed). 2020;12:139-49. [Crossref]  [PubMed] 
  65. Takaoka M. Takaoka M. Resveratrol (3,4′,5-trihydroxy-trans-stilbene; Fig. 1) was first isolated in 1939 by Takaoka from Veratrum grandiflorum O. Loes (root of the white hellebore). J Chem Soc Jpn. 1939;60:1090-100. [Crossref] 
  66. Baur JA, Sinclair DA. Therapeutic potential of resveratrol: the in vivo evidence. Nat Rev Drug Discov. 2006;5(6):493-506. [Crossref]  [PubMed] 
  67. Gan Z, Wei W, Wu J, Zhao Y, Zhang L, Wang T, et al. Resveratrol and curcumin improve intestinal mucosal integrity and decrease m6A RNA methylation in the intestine of weaning piglets. ACS Omega. 2019;4(17):17438-46. [Crossref]  [PubMed]  [PMC] 
  68. Zhang Y, Wang G, Wang T, Cao W, Zhang L, Chen X. Nrf2-Keap1 pathway-mediated effects of resveratrol on oxidative stress and apoptosis in hydrogen peroxide-treated rheumatoid arthritis fibroblast-like synoviocytes. Ann N Y Acad Sci. 2019;1457(1):166-78. [Crossref]  [PubMed] 
  69. Yang G, Chang CC, Yang Y, Yuan L, Xu L, Ho CT, et al. Resveratrol alleviates rheumatoid arthritis via reducing ROS and inflammation, inhibiting MAPK signaling pathways, and suppressing angiogenesis. J Agric Food Chem. 2018;66(49):12953-60. [Crossref]  [PubMed] 
  70. Yeung F, Hoberg JE, Ramsey CS, Keller MD, Jones DR, Frye RA, et al. Modulation of NF-kappaB-dependent transcription and cell survival by the SIRT1 deacetylase. EMBO J. 2004;23(12):2369-80. [Crossref]  [PubMed]  [PMC] 
  71. Lomholt S, Mellemkjaer A, Iversen MB, Pedersen SB, Kragstrup TW. Resveratrol displays anti-inflammatory properties in an ex vivo model of immune mediated inflammatory arthritis. BMC Rheumatol. 2018;2:27. [Crossref]  [PubMed]  [PMC] 
  72. Khojah HM, Ahmed S, Abdel-Rahman MS, Elhakeim EH. Resveratrol as an effective adjuvant therapy in the management of rheumatoid arthritis: a clinical study. Clin Rheumatol. 2018;37(8):2035-42. [Crossref]  [PubMed] 
  73. Pezzuto JM. Resveratrol: twenty years of growth, development and controversy. Biomol Ther (Seoul). 2019;27(1):1-14. [Crossref]  [PubMed]  [PMC] 
  74. Bao J, Dai SM. A Chinese herb Tripterygium wilfordii Hook F in the treatment of rheumatoid arthritis: mechanism, efficacy, and safety. Rheumatol Int. 2011;31(9):1123-9. [Crossref]  [PubMed] 
  75. Chen SR, Dai Y, Zhao J, Lin L, Wang Y, Wang Y. A mechanistic overview of triptolide and celastrol, natural products from Tripterygium wilfordii Hook F. Front Pharmacol. 2018;9:104. [Crossref]  [PubMed]  [PMC] 
  76. Venkatesha SH, Yu H, Rajaiah R, Tong L, Moudgil KD. Celastrus-derived celastrol suppresses autoimmune arthritis by moulating antigen-induced cellular and humoral effector responses. J Biol Chem. 2011;286(17):15138-46. [Crossref]  [PubMed]  [PMC] 
  77. Liu J, Lee J, Salazar Hernandez MA, Mazitschek R, Ozcan U. Treatment of obesity with celastrol. Cell. 2015;161(5):999-1011. [Crossref]  [PubMed]  [PMC] 
  78. Jiang M, Zha Q, Zhang C, Lu C, Yan X, Zhu W, et al. Predicting and verifying outcome of Tripterygium wilfordii Hook F. based therapy in rheumatoid arthritis: from open to double-blinded randomized trial. Sci Rep. 2015;5:9700. [Crossref]  [PubMed]  [PMC] 
  79. Haqqi TM, Anthony DD, Gupta S, Ahmad N, Lee MS, Kumar GK, et al. Prevention of collagen-induced arthritis in mice by a polyphenolic fraction from green tea. Proc Natl Acad Sci U S A. 1999;96(8):4524-9. [Crossref]  [PubMed]  [PMC] 
  80. Ahmed S, Marotte H, Kwan K, Ruth JH, Campbell PL, Rabquer BJ, et al. Epigallocatechin-3-gallate inhibits IL-6 synthesis and suppresses transsignaling by enhancing soluble gp130 production. Proc Natl Acad Sci U S A. 2008;105(38):14692-7. [Crossref]  [PubMed]  [PMC] 
  81. Pervin M, Unno K, Takagaki A, Isemura M, Nakamura Y. Function of green tea catechins in the brain: epigallocatechin gallate and its metabolites. Int J Mol Sci. 2019;20(15):3630. [Crossref]  [PubMed]  [PMC] 
  82. Oliviero F, Scanu A, Zamudio-Cuevas Y, Punzi L, Spinella P. Anti-inflammatory effects of polyphenols in arthritis. J Sci Food Agric. 2018;98(5):1653-9. [Crossref]  [PubMed] 
  83. Bhutia Pemba H, Sharangi Baran AB, Lepcha R, Tamang D. Bioactive compounds and antioxidant properties of tea: status, global research and potentialities. J Tea Sci Res. 2015;5(11):1-13. [Crossref] 
  84. Ramadan G, El-Beih NM, Talaat RM, Abd El-Ghffar EA. Anti-inflammatory activity of green versus black tea aqueous extract in a rat model of human rheumatoid arthritis. Int J Rheum Dis. 2017;20(2):203-13. [Crossref]  [PubMed] 
  85. Min SY, Yan M, Kim SB, Ravikumar S, Kwon SR, Vanarsa K, et al. Green tea epigallocatechin-3-gallate suppresses autoimmune arthritis through indoleamine-2,3-dioxygenase expressing dendritic cells and the nuclear factor, erythroid 2-like 2 antioxidant pathway. J Inflamm (Lond). 2015;12:53. [Crossref]  [PubMed]  [PMC] 
  86. Wang H, Li S, Zhang G, Wu H, Chang X. Potential therapeutic effects of cyanidin-3-O-glucoside on rheumatoid arthritis by relieving inhibition of CD38+ NK cells on Treg cell differentiation. Arthritis Res Ther. 2019;21(1):220. [Crossref]  [PubMed]  [PMC] 
  87. Rambod M, Nazarinia M, Raieskarimian F. The impact of dietary habits on the pathogenesis of rheumatoid arthritis: a case-control study. Clin Rheumatol. 2018;37(10):2643-8. [Crossref]  [PubMed] 
  88. Lamichhane D, Collins C, Constantinescu F, Walitt B, Pettinger M, Parks C, et al. Coffee and tea consumption in relation to risk of rheumatoid arthritis in the women's health ınitiative observational cohort. J Clin Rheumatol. 2019;25(3):127-132. [Crossref]  [PubMed]  [PMC] 
  89. Henning SM, Niu Y, Lee NH, Thames GD, Minutti RR, Wang H, et al. Bioavailability and antioxidant activity of tea flavanols after consumption of green tea, black tea, or a green tea extract supplement. Am J Clin Nutr. 2004;80(6):1558-64. [Crossref]  [PubMed] 
  90. Maeda Y, Takeda K. Role of gut microbiota in rheumatoid arthritis. J Clin Med. 2017;6(6):60. [Crossref]  [PubMed]  [PMC] 
  91. Marteau P. Probiotics, prebiotics, synbiotics: ecological treatment for inflammatory bowel disease? Gut. 2006;55(12):1692-3. [Crossref]  [PubMed]  [PMC] 
  92. Sanders ME. Probiotics: considerations for human health. Nutr Rev. 2003;61(3):91-9. [Crossref]  [PubMed]  [PMC] 
  93. Scher JU, Sczesnak A, Longman RS, Segata N, Ubeda C, Bielski C, et al. Expansion of intestinal Prevotella copri correlates with enhanced susceptibility to arthritis. Elife. 2013;2:e01202. [Crossref]  [PubMed]  [PMC] 
  94. Teng F, Klinger CN, Felix KM, Bradley CP, Wu E, Tran NL, et al. Gut microbiota drive autoimmune arthritis by promoting differentiation and migration of Peyer's patch T follicular helper cells. Immunity. 2016;44(4):875-88. [Crossref]  [PubMed]  [PMC] 
  95. Yue M, Xia Y, Shi C, Guan C, Li Y, Liu R, et al. Berberine ameliorates collagen-induced arthritis in rats by suppressing Th17 cell responses via inducing cortistatin in the gut. FEBS J. 2017;284(17):2786-801. [Crossref]  [PubMed] 
  96. Yue M, Tao Y, Fang Y, Lian X, Zhang Q, Xia Y, et al. The gut microbiota modulator berberine ameliorates collagen-induced arthritis in rats by facilitating the generation of butyrate and adjusting the intestinal hypoxia and nitrate supply. FASEB J. 2019;33(11):12311-23. [Crossref]  [PubMed]  [PMC] 
  97. Toden S, Bird AR, Topping DL, Conlon MA. Dose-dependent reduction of dietary protein-induced colonocyte DNA damage by resistant starch in rats correlates more highly with caecal butyrate than with other short chain fatty acids. Cancer Biol Ther. 2007;6(2):253-8. [Crossref]  [PubMed] 
  98. Bäckhed F, Ding H, Wang T, Hooper LV, Koh GY, Nagy A, et al. The gut microbiota as an environmental factor that regulates fat storage. Proc Natl Acad Sci U S A. 2004;101(44):15718-23. [Crossref]  [PubMed]  [PMC] 
  99. McInnes IB, Schett G. The pathogenesis of rheumatoid arthritis. N Engl J Med. 2011;365(23):2205-19. [Crossref]  [PubMed] 
  100. Clemente JC, Ursell LK, Parfrey LW, Knight R. The impact of the gut microbiota on human health: an integrative view. Cell. 2012;148(6):1258-70. [Crossref]  [PubMed]  [PMC] 
  101. Zhang X, Zhang D, Jia H, Feng Q, Wang D, Liang D, et al. The oral and gut microbiomes are perturbed in rheumatoid arthritis and partly normalized after treatment. Nat Med. 2015;21(8):895-905. [Crossref]  [PubMed] 
  102. Whitehouse MW. Rheumatoid arthritis and tuberculosis. Lancet. 1986;328(8508):688-9. [Crossref] 
  103. Holoshitz J, Klajman A, Drucker I, Lapidot Z, Yaretzky A, Frenkel A, et al. T lymphocytes of rheumatoid arthritis patients show augmented reactivity to a fraction of mycobacteria cross-reactive with cartilage. Lancet. 1986;2:305-09. [Crossref]  [PubMed] 
  104. Jethwa H, Abraham S. The evidence for microbiome manipulation in inflammatory arthritis. Rheumatology (Oxford). 2017;56(9): 1452-60. [PubMed] 
  105. Kim MS, Hwang SS, Park EJ, Bae JW. Strict vegetarian diet improves the risk factors associated with metabolic diseases by modulating gut microbiota and reducing intestinal inflammation. Environ Microbiol Rep. 2013;5(5):765-75. [Crossref]  [PubMed] 
  106. Alwarith J, Kahleova H, Rembert E, Yonas W, Dort S, Calcagno M, et al. Nutrition interventions in rheumatoid arthritis: the potential use of plant-based diets. A Review. Front Nutr. 2019;6:141. [Crossref]  [PubMed]  [PMC] 
  107. Berthelot JM ,Sellam J, Maugars Y, Berenbaum F. Cartilage-gut-microbiome axis: a new paradigm for novel therapeutic opportunities in osteoarthritis. RMD Open. 2019;5(2): e001037. [Crossref]  [PubMed]  [PMC] 
  108. Woolf SH, Purnell JQ. The good life: working together to promote opportunity and improve population health and well-being. JAMA. 2016;315(16):1706-8. [Crossref]  [PubMed] 
  109. Ordovas JM, Corella D. Nutritional genomics. Annu Rev Genomics Hum Genet. 2004;5:71-118. [Crossref]  [PubMed] 
  110. Ordovas JM, Ferguson LR, Tai ES, Mathers JC. Personalised nutrition and health. BMJ. 2018;361:bmj.k2173. [Crossref]  [PubMed]  [PMC] 
  111. Nair N, Wilson AG. Can machine learning predict responses to TNF inhibitors? Nat Rev Rheumatol. 2019:702-4. [Crossref]  [PubMed] 
  112. DellaPenna D. Nutritional genomics: manipulating plant micronutrients to improve human health. Science. 1999;285(5426):375-9. [Crossref]  [PubMed] 
  113. Garrod AE. The incidence of alkaptonuria: a study in chemical individuality. Lancet. 1902;2,1616-20. [Crossref] 
  114. Leng G, Adan RAH, Belot M, Brunstrom JM, de Graaf K, Dickson SL, et al. The determinants of food choice. Proc Nutr Soc. 2017;76(3):316-27. [Crossref]  [PubMed] 
  115. Khanna S, Jaiswal KS, Gupta B. Managing rheumatoid arthritis with dietary interventions. Front Nutr. 2017;4:52. [Crossref]  [PubMed]  [PMC] 
  116. Scott DL, Wolfe F, Huizinga TWJ. Rheumatoid arthritis. Lancet. 2010;376(9746):1094-108. [Crossref]  [PubMed] 
  117. El-Sohemy A. Nutrigenetics. Forum Nutr. 2007;60:25-30. [Crossref]  [PubMed] 
  118. Müller M, Kersten S. Nutrigenomics: goals and strategies. Nat Rev Genet. 2003;4(4):315-22. [Crossref]  [PubMed] 
  119. Willett WC. Balancing life-style and genomics research for disease prevention. Science. 2002;296(5568):695-8. [Crossref]  [PubMed] 

.: Up To Date

Login

 Forgot your password?

 New Registration  

Contact

Ortadoğu Reklam Tanıtım Yayıncılık Turizm Eğitim İnşaat Sanayi ve Ticaret A.Ş.

.: Address

Turkocagi Caddesi No:30 06520 Balgat / ANKARA
Phone: +90 312 286 56 56
Fax: +90 312 220 04 70
E-mail: info@turkiyeklinikleri.com

.: Manuscript Editing Department

Phone: +90 312 286 56 56/ 2
E-mail: yaziisleri@turkiyeklinikleri.com

.: English Language Redaction

Phone: +90 312 286 56 56/ 145
E-mail: tkyayindestek@turkiyeklinikleri.com

.: Marketing Sales-Project Department

Phone: +90 312 286 56 56/ 142
E-mail: reklam@turkiyeklinikleri.com

.: Subscription and Public Relations Department

Phone: +90 312 286 56 56/ 118
E-mail: abone@turkiyeklinikleri.com

.: Customer Services

Phone: +90 312 286 56 56/ 118
E-mail: satisdestek@turkiyeklinikleri.com

1. TERMS OF USE

1.1. To use the web pages with http://www.turkiyeklinikleri.com domain name or the websites reached through the sub domain names attached to the domain name (They will be collectively referred as "SITE"), please read the conditions below. If you do not accept these terms, please cease to use the "SITE." "SITE" owner reserves the right to change the information on the website, forms, contents, the "SITE," "SITE" terms of use anytime they want.

1.2. The owner of the "SITE" is Ortadoğu Advertisement Presentation Publishing Tourism Education Architecture Industry and Trade Inc. (From now on it is going to be referred as "Turkiye Klinikleri", shortly) and it resides at Turkocagi cad. No:30, 06520 Balgat Ankara. The services in the "SITE" are provided by "Turkiye Klinikleri."

1.3. Anyone accessing the "SITE" with or without a fee whether they are a natural person or a legal identity is considered to agree these terms of use. In this contract hereby, "Turkiye Klinikleri" may change the stated terms anytime. These changes will be published in the "SITE" periodically and they will be valid when they are published. Any natural person or legal identity benefiting from and reaching to the "SITE" are considered to be agreed to any change on hereby contract terms done by "Turkiye Klinikleri."

1.4. The "Terms of Use" hereby is published in the website with the last change on March 30th 2014 and the "SITE" is activated by enabling the access to everyone. The "Terms of Use" hereby is also a part of the any "USER Contract" was and/or will be done with the users using "Turkiye Klinikleri" services with or without a fee an inseparable.

2. DEFINITIONS

2.1. "SITE": A website offering different kind of services and context with a certain frame determined by "Turkiye Klinikleri" and it is accessible on-line on http://www.turkiyeklinikleri.com domain name and/or subdomains connected to the domain name.

2.2. USER: A natural person or a legal identity accessing to the "SITE" through online settings.

2.3. LINK: A link enabling to access to another website through the "SITE", the files, the context or through another website to the "SITE", the files and the context.

2.4. CONTEXT: Any visual, literary and auditory images published in the "Turkiye Klinikleri", "SITE" and/or any website or any accessible information, file, picture, number/figures, price, etc.

2.5. "USER CONTRACT": An electronically signed contract between a natural or a legal identity benefiting from special services "Turkiye Klinikleri" will provide and "Turkiye Klinikleri".

3. SCOPE OF THE SERVICES

3.1. "Turkiye Klinikleri" is completely free to determine the scope and quality of the services via the "SITE".

3.2. To benefit the services of "Turkiye Klinikleri" "SITE", the "USER" must deliver the features that will be specified by "Turkiye Klinikleri". "Turkiye Klinikleri" may change this necessity any time single-sided.

3.3. Not for a limited number, the services "Turkiye Klinikleri" will provide through the "SITE" for a certain price or for free are;

- Providing scientific articles, books and informative publications for health industry.

- Providing structural, statistical and editorial support to article preparation stage for scientific journals.

4. GENERAL PROVISIONS

4.1. "Turkiye Klinikleri" is completely free to determine which of the services and contents provided in the "SITE" will be charged.

4.2. People benefiting from the services provided by "Turkiye Klinikleri" and using the website can use the "SITE" only according to the law and only for personal reasons. Users have the criminal and civil liability for every process and action they take in the "SITE". Every USER agrees, declares and undertakes that they will not proceed by any function or action infringement of rights of "Turkiye Klinikleri"s and/or other third parties', they are the exclusive right holder on usage, processing, storage, made public and revealing any written, visual or auditory information reported to Turkiye Klinikleri" and/or "SITE" to the third parties. "USER" agrees and undertakes that s/he will not duplicate, copy, distribute, process, the pictures, text, visual and auditory images, video clips, files, databases, catalogs and lists within the "SITE", s/he will not be using these actions or with other ways to compete with "Turkiye Klinikleri", directly or indirectly.

4.3. The services provided and the context published within the "SITE" by third parties is not under the responsibility of "Turkiye Klinikleri", institutions collaborated with "Turkiye Klinikleri", "Turkiye Klinikleri" employee and directors, "Turkiye Klinikleri" authorized salespeople. Commitment to accuracy and legality of the published information, context, visual and auditory images provided by any third party are under the full responsibility of the third party. "Turkiye Klinikleri" does not promise and guarantee the safety, accuracy and legality of the services and context provided by a third party.

4.4. "USER"s cannot act against "Turkiye Klinikleri", other "USER"s and third parties by using the "SITE". "Turkiye Klinikleri" has no direct and/or indirect responsibility for any damage a third party suffered or will suffer regarding "USER"s actions on the "SITE" against the rules of the hereby "Terms of Use" and the law.

4.5. "USER"s accept and undertake that the information and context they provided to the "SITE" are accurate and legal. "Turkiye Klinikleri" is not liable and responsible for promising and guaranteeing the verification of the information and context transmitted to "Turkiye Klinikleri" by the "USER"s, or uploaded, changed and provided through the "SITE" by them and whether these information are safe, accurate and legal.

4.6. "USER"s agree and undertake that they will not perform any action leading to unfair competition, weakening the personal and commercial credit of "Turkiye Klinikleri" and a third party,  encroaching and attacking on personal rights within the "SITE" in accordance with the Turkish Commercial Code Law.

4.7. "Turkiye Klinikleri" reserves the right to change the services and the context within the "SITE"  anytime. "Turkiye Klinikleri" may use this right without any notification and timelessly. "USER"s have to make the changes and/or corrections "Turkiye Klinikleri" required immediately. Any changes and/or corrections that are required by "Turkiye Klinikleri", may be made by "Turkiye Klinikleri" when needed. Any harm, criminal and civil liability resulted or will result from changes and/or corrections required by "Turkiye Klinikleri" and were not made on time by the "USER"s belongs completely to the users.

4.8. "Turkiye Klinikleri" may give links through the "SITE" to other websites and/or "CONTEXT"s and/or folders that are outside of their control and owned and run by third parties. These links are provided for ease of reference only and do not hold qualification for support the respective web SITE or the admin or declaration or guarantee for the information inside. "Turkiye Klinikleri" does not hold any responsibility over the web-sites connected through the links on the "SITE", folders and context, the services or products on the websites provided through these links or their context.

4.9. "Turkiye Klinikleri" may use the information provided to them by the "USERS" through the "SITE" in line with the terms of the "PRIVACY POLICY" and "USER CONTRACT". It may process the information or classify and save them on a database. "Turkiye Klinikleri" may also use the USER's or visitor's identity, address, e-mail address, phone number, IP number, which sections of the "SITE" they visited, domain type, browser type, date and time information to provide statistical evaluation and customized services.

5. PROPRIETARY RIGHTS

5.1. The information accessed through this "SITE" or provided by the users legally and all the elements (including but not limited to design, text, image, html code and other codes) of the "SITE" (all of them will be called as studies tied to "Turkiye Klinikleri"s copyrights) belongs to "Turkiye Klinikleri". Users do not have the right to resell, process, share, distribute, display or give someone permission to access or to use the "Turkiye Klinikleri" services, "Turkiye Klinikleri" information and the products under copyright protection by "Turkiye Klinikleri". Within hereby "Terms of Use" unless explicitly permitted by "Turkiye Klinikleri" nobody can reproduce, process, distribute or produce or prepare any study from those under "Turkiye Klinikleri" copyright protection.

5.2. Within hereby "Terms of Use", "Turkiye Klinikleri" reserves the rights for "Turkiye Klinikleri" services, "Turkiye Klinikleri" information, the products associated with "Turkiye Klinikleri" copyrights, "Turkiye Klinikleri" trademarks, "Turkiye Klinikleri" trade looks or its all rights for other entity and information it has through this website unless it is explicitly authorized by "Turkiye Klinikleri".

6. CHANGES IN THE TERMS OF USE

"Turkiye Klinikleri" in its sole discretion may change the hereby "Terms of Use" anytime announcing within the "SITE". The changed terms of the hereby "Terms of Use" will become valid when they are announced. Hereby "Terms of Use" cannot be changed by unilateral declarations of users.

7. FORCE MAJEURE

"Turkiye Klinikleri" is not responsible for executing late or never of this hereby "Terms of Use", privacy policy and "USER Contract" in any situation legally taken into account as force majeure. Being late or failure of performance or non-defaulting of this and similar cases like this will not be the case from the viewpoint of "Turkiye Klinikleri", and "Turkiye Klinikleri" will not have any damage liability for these situations. "Force majeure" term will be regarded as outside of the concerned party's reasonable control and any situation that "Turkiye Klinikleri" cannot prevent even though it shows due diligence. Also, force majeure situations include but not limited to natural disasters, rebellion, war, strike, communication problems, infrastructure and internet failure, power cut and bad weather conditions.

8. LAW AND AUTHORISATION TO FOLLOW

Turkish Law will be applied in practicing, interpreting the hereby "Terms of Use" and managing the emerging legal relationships within this "Terms of Use" in case of finding element of foreignness, except for the rules of Turkish conflict of laws. Ankara Courts and Enforcement Offices are entitled in any controversy happened or may happen due to hereby contract.

9. CLOSING AND AGREEMENT

Hereby "Terms of Use" come into force when announced in the "SITE" by "Turkiye Klinikleri". The users are regarded to agree to hereby contract terms by using the "SITE". "Turkiye Klinikleri" may change the contract terms and the changes will be come into force by specifying the version number and the date of change on time it is published in the "SITE".

 

30.03.2014

Privacy Policy

We recommend you to read the terms of use below before you visit our website. In case you agree these terms, following our rules will be to your favor. Please read our Terms of Use thoroughly.

www.turkiyeklinikleri.com website belongs to Ortadoğu Advertisement Presentation Publishing Tourism Education Architecture Industry and Trade Inc. and is designed in order to inform physicians in the field of health

www.turkiyeklinikleri.com cannot reach to user’s identity, address, service providers or other information. The users may send this information to the website through forms if they would like to. However, www.turkiyeklinikleri.com may collect your hardware and software information. The information consists of your IP address, browser type, operating system, domain name, access time, and related websites. www.turkiyeklinikleri.com cannot sell the provided user information (your name, e-mail address, home and work address, phone number) to the third parties, publish it publicly, or keep it in the website. Gathered information has a directing feature to be a source for the website’s visitor profile, reporting and promotion of the services.

www.turkiyeklinikleri.com uses the taken information:

-To enhance, improve and maintain the quality of the website

-To generate visitor’s profile and statistical data

-To determine the tendency of the visitors on using our website

-To send print publications/correspondences

-To send press releases or notifications through e-mail

-To generate a list for an event or competition

By using www.turkiyeklinikleri.com you are considered to agree that;

-Ortadoğu Advertisement Presentation Publishing Tourism Education Architecture Industry and Trade Inc. cannot be hold responsible for any user’s illegal and immoral behavior,

-Terms of use may change from time to time,

-It is not responsible for other websites’ contents it cannot control or the harms they may cause although it uses the connection they provided.

Ortadoğu Advertisement Presentation Publishing Tourism Education Architecture Industry and Trade Inc. may block the website to users in the following events:

-Information with wrong, incomplete, deceiving or immoral expressions is recorded to the website,

-Proclamation, advertisement, announcement, libelous expressions are used against natural person or legal identity,

-During various attacks to the website,

-Disruption of the website because of a virus.

Written, visual and audible materials of the website, including the code and the software are under protection by legal legislation.

Without the written consent of Ortadoğu Advertisement Presentation Publishing Tourism Education Architecture Industry and Trade Inc. the information on the website cannot be downloaded, changed, reproduced, copied, republished, posted or distributed.

All rights of the software and the design of the website belong to Ortadoğu Advertisement Presentation Publishing Tourism Education Architecture Industry and Trade Inc.

Ortadoğu Advertisement Presentation Publishing Tourism Education Architecture Industry and Trade Inc. will be pleased to hear your comments about our terms of use. Please share the subjects you think may enrich our website or if there is any problem regarding our website.

info@turkiyeklinikleri.com