Öz
Flavonoids are widely used phenolic compounds in traditional medicine due to their health-beneficial features. Quercetin is a remarkable member of flavonols, which is a sub-family of flavonoids, with its broad biological activity. Using flavonoids as adjuvant agents in the treatment of diabetes mellitus is frequently being debated. Inflammation, which is mentioned in the pathophysiology of diabetes, may be seen as a target for the adjuvant therapy. Thereby, in the present study, we aimed to investigate the effects of quercetin on the plasma inflammatory cytokines, namely interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in diabetic rats. Total six groups were assigned as controls and treatments (50 mg/kg and 100 mg/kg quercetin) in diabetic and non-diabetic main groups. We found that diabetes resulted in a significant increase of plasma IL-6 and TNF-α levels (respectively p=0,01 and p=0,01). Both doses of quercetin reduced plasma IL-6 and TNF-α to the levels that in non-diabetic animals (respectively p=0,01 and p=0,01). In terms of inflammatory cytokine levels, there was no significance between non-diabetic quercetin injected and control animals (p=0,99). Therefore, we assumed that quercetin acts as an immunomodulator rather than an immunosuppressant in diabetic rats
Anahtar Kelimeler
Quercetin diabetes mellitus inflammation interleukin-6 tumor necrosis factor-α
Kaynakça
- International Diabetes Federation. IDF Diabetes Atlas, 6th
- ed.th ed. 2013 [cited 2014 Feb 12]. Available from URL:
- http://www.idf.org/diabetesatlas.
- Bending D, Zaccone P, Cooke A. Inflammation and type one
- diabetes. International Immunology. 2012;24(6); 339–346.
- Kahn SE, Cooper ME, Del Prato S. Pathophysiology and
- treatment of type 2 diabetes: perspectives on the past,
- present, and future. The Lance. 2014;383(9922); 1068–1083.
- Cade WT. Diabetes-related microvascular and
- macrovascular diseases in the physical therapy setting.
- Physical Therapy. 2008;88(11); 1322–1335.
- Gabay C. Interleukin-6 and chronic inflammation. Arthritis
- Research & Therapy. 2006;8 Suppl 2; S3.
- Senn JJ, Klover PJ, Nowak IA, Mooney RA. Interleukin-6
- Induces Cellular Insulin Resistance in Hepatocytes. Diabetes.
- ;51(12); 3391–3399.
- Rotter V, Nagaev I, Smith U. Interleukin-6 (IL-6) induces
- insulin resistance in 3T3-L1 adipocytes and is, like IL-8 and
- tumor necrosis factor-alpha, overexpressed in human fat cells
- from insulin-resistant subjects. The Journal of Biological
- Chemistry. 2003;278(46); 45777–45784.
- Nieto-Vazquez I, Fernandez-Veledo S, Kramer DK, Vila-
- Bedmar R, Garcia-Guerra L, Lorenzo M. Insulin resistance
- associated to obesity: the link TNF-alpha. Archives of
- Physiology and Biochemistry. 2008;114(3); 183–194.
- Kumar S, Pandey AK. Chemistry and biological activities of
- flavonoids: an overview. The Scientific World Journal.
- ;2013; 162750.
- Formica JV, Regelson W. Review of the biology of
- Quercetin and related bioflavonoids. Food and Chemical
- Toxicology. 1995;33(12); 1061–1080.
- Kelly GS. Quercetin. Monograph. Alternative Medicine
- Review. 2011;16(2); 172–194.
- Kanter M. Protective effects of thymoquinone on
- streptozotocin-induced diabetic nephropathy. Journal of
- Molecular Histology. 2009;40(2); 107–115.
- Akash, Muhammad Sajid Hamid, Rehman K, Chen S. Role
- of inflammatory mechanisms in pathogenesis of type 2
- diabetes mellitus. Journal of Cellular Biochemistry.
- ;114(3); 525–531.
- King GL. The role of inflammatory cytokines in diabetes
- and its complications. Journal of Periodontology. 2008;79(8
- Suppl); 1527–1534.
- Bottino R, Lemarchand P, Trucco M, Giannoukakis N. Gene-
- and cell-based therapeutics for type I diabetes mellitus.
- Gene Therapy. 2003;10(10); 875–889.
- Nicholas D, Odumosu O, Langridge, William H R.
- Autoantigen based vaccines for type 1 diabetes. Discovery
- Medicine. 2011;11(59); 293–301.
- Phillips JM, Parish NM, Raine T, Bland C, Sawyer Y, De La
- Peña, Hugo ve ark. Type 1 diabetes development requires
- both CD4+ and CD8+ T cells and can be reversed by nondepleting
- antibodies targeting both T cell populations. The
- Review of Diabetic Studies 2009;6(2); 97–103.
- Hamilton-Williams EE, Palmer SE, Charlton B, Slattery RM.
- Beta cell MHC class I is a late requirement for diabetes.
- Proceedings of the National Academy of Sciences.
- ;100(11); 6688–6693.
- Pinkse, Gabrielle G M, Tysma, Odette H M, Bergen, Cees A
- M, Kester, Michel G D, Ossendorp F, van Veelen, Peter A ve
- ark. Autoreactive CD8 T cells associated with beta cell
- destruction in type 1 diabetes. Proceedings of the National
- Academy of Sciences. 2005;102(51); 18425–18430.
- Wedrychowicz A, Dziatkowiak H, Sztefko K. Interleukin-6
- (IL-6) and IGF-IGFBP system in children and adolescents with
- type 1 diabetes mellitus. Experimental and Clinical
- Endocrinology & Diabetes. 2013;112(8); 435–439.
- Snell-Bergeon JK, West NA, Mayer-Davis EJ, Liese AD,
- Marcovina SM, D'Agostino, Ralph B Jr ve ark. Inflammatory
- markers are increased in youth with type 1 diabetes: the
- SEARCH Case-Control study. The Journal of Clinical
- Endocrinology & Metabolism. 2010;95(6); 2868–2876.
- Choi S, Choi K, Yoon I, Shin J, Kim J, Park W ve ark. IL-6
- protects pancreatic islet beta cells from pro-inflammatory
- cytokines-induced cell death and functional impairment in
- vitro and in vivo. Transplant Immunology. 2004;13(1); 43–53.
- Campbell IL, Hobbs MV, Dockter J, Oldstone MB, Allison J.
- Islet inflammation and hyperplasia induced by the pancreatic
- islet-specific overexpression of interleukin-6 in transgenic
- mice. American Journal of Pathology. 1994;145(1); 157–166.
- Wegner M, Araszkiewicz A, Piorunska-Stolzmann M,
- Wierusz-Wysocka B, Zozulinska-Ziolkiewicz D. Association
- Between IL-6 Concentration and Diabetes-Related Variables in
- DM1 Patients with and without Microvascular Complications.
- Inflammation. 2013;36(3); 723–728.
- Lee L, Xu B, Michie SA, Beilhack GF, Warganich T, Turley S
- ve ark. The role of TNF-alpha in the pathogenesis of type 1
- diabetes in the nonobese diabetic mouse: analysis of dendritic
- cell maturation. Proceedings of the National Academy of
- Sciences. 2005;102(44); 15995–16000.
- Koulmanda M, Bhasin M, Awdeh Z, Qipo A, Fan Z,
- Hanidziar D ve ark. The role of TNF-α in mice with type 1- and
- - diabetes. PLoS ONE. 2012;7(5); e33254.
- Garber AJ. Obesity and type 2 diabetes: which patients are
- at risk? Diabetes, Obesity and Metabolism. 2012;14(5); 399–
- -
- Yki-Järvinen H, Ryysy L, Kauppila M, Kujansuu E, Lahti J,
- Marjanen T ve ark. Effect of obesity on the response to insulin
- therapy in noninsulin-dependent diabetes mellitus. The
- Journal of Clinical Endocrinology & Metabolism. 1997;82(12);
- –4043.
- Cruz NG, Sousa LP, Sousa MO, Pietrani NT, Fernandes AP,
- Gomes KB. The linkage between inflammation and Type 2
- diabetes mellitus. Diabetes Research and Clinical Practice.
- ;99(2); 85–92.
- Zozulinska D, Wierusz-Wysocka B. Type 2 diabetes
- mellitus as inflammatory disease. Diabetes Research and
- Clinical Practice. 2006;74(2); S12.
- Rivera L, Morón R, Sánchez M, Zarzuelo A, Galisteo M.
- Quercetin ameliorates metabolic syndrome and improves the
- inflammatory status in obese Zucker rats. Obesity. 2008;16(9);
- –2087.
- Chuang C, Martinez K, Xie G, Kennedy A, Bumrungpert A,
- Overman A ve ark. Quercetin is equally or more effective than
- resveratrol in attenuating tumor necrosis factor- -mediated
- inflammation and insulin resistance in primary human
- adipocytes. American Journal of Clinical Nutrition. 2010;92(6);
- –1521.
- Zahedi M, Ghiasvand R, Feizi A, Asgari G, Darvish L. Does
- Quercetin Improve Cardiovascular Risk factors and
- Inflammatory Biomarkers in Women with Type 2 Diabetes: A
- Double-blind Randomized Controlled Clinical Trial.
- International Journal of Preventive Medicine. 2013;4(7); 777–
- -
- Egert S, Bosy-Westphal A, Seiberl J, Kürbitz C, Settler U,
- Plachta-Danielzik S ve ark. Quercetin reduces systolic blood
- pressure and plasma oxidised low-density lipoprotein
- concentrations in overweight subjects with a highcardiovascular
- disease risk phenotype: a double-blinded,
- placebo-controlled cross-over study. British Journal of
- Nutrition. 2009;102(7); 1065–1074.
- Manach C, Williamson G, Morand C, Scalbert A, Remesy C.
- Bioavailability and bioefficacy of polyphenols in humans. I.
- Review of 97 bioavailability studies. The American Journal of
- Clinical Nutrition. 2005;81(1 Suppl); 230S-242S.
- . 2011; 112 (6): 318-22.
- Noyan T, Balahoroğlu R, Kömüroğlu U. The Effects of Vitamin
- A, E, and C Combined Insulin Treatments on the
- Antioxidant Enzymes in the Diabetic Rats. Türk Klinik Biyokimya
- Derg. 2004; 2(3): 113-119.
Öz
Flavonoidler sağlık açısından faydalarına istinaden geleneksel tıpta yaygın kullanılan fenolik bileşiklerdir. Flavonoidlerin alt ailesi
olan flavonoller içerisinde kuersetin, yüksek biyolojik aktivitesi ile dikkat çekmektedir. Flavonoidlerin diyabetes mellitus tedavisinde
destekleyici ajanlar olarak kullanılması sıkça tartışılmaktadır. Diyabet fizyopatogenezinde söz edilen inflamasyon, destekleyici
tedavi açısından bir hedef olarak görülebilir. Buradan hareketle mevcut çalışmamızda diyabetik sıçanlarda kuersetinin
plazma inflamatuar sitokinlerinden olan interlökin-6 (IL-6) ve tümör nekroz faktör-α (TNF-α) seviyelerine etkisinin araştırılması
amaçlanmıştır. Diyabetik ve non-diyabetik iki ana grup içerisinde kontrol ve tedavi (50 mg/kg ve 100 mg/kg kuersetin) olmak
üzere toplam altı alt grup oluşturulmuştur. Diyabetik hayvanlarda plazma IL-6 ve TNF-α seviyelerinde önemli düzeyde artış izlenmiştir
(sırasıyla p=0,01 ve p=0,01). Her iki kuersetin dozu diyabetik hayvanlarda yükselen plazma IL-6 ve TNF-α seviyelerinin
non-diyabetik hayvanlar düzeyine düşürülmesini sağlamıştır (sırasıyla p=0,01 ve p=0,01). İnflamatuar sitokin seviyeleri açısından
diyabetik olmayan sıçanlarda kuersetin enjeksiyonu yapılan ve yapılmayan hayvanlar arasında farka rastlanmamıştır
(p=0,99). Bu bulgular kuersetinin diyabetik sıçanlarda immünosupresandan ziyade immünomodülatör olarak davrandığını düşündürmektedir.
Anahtar Kelimeler:
Anahtar Kelimeler
Kuersetin diyabetes mellitus inflamasyon interlökin-6 tümör nekroz faktör-α
Kaynakça
- International Diabetes Federation. IDF Diabetes Atlas, 6th
- ed.th ed. 2013 [cited 2014 Feb 12]. Available from URL:
- http://www.idf.org/diabetesatlas.
- Bending D, Zaccone P, Cooke A. Inflammation and type one
- diabetes. International Immunology. 2012;24(6); 339–346.
- Kahn SE, Cooper ME, Del Prato S. Pathophysiology and
- treatment of type 2 diabetes: perspectives on the past,
- present, and future. The Lance. 2014;383(9922); 1068–1083.
- Cade WT. Diabetes-related microvascular and
- macrovascular diseases in the physical therapy setting.
- Physical Therapy. 2008;88(11); 1322–1335.
- Gabay C. Interleukin-6 and chronic inflammation. Arthritis
- Research & Therapy. 2006;8 Suppl 2; S3.
- Senn JJ, Klover PJ, Nowak IA, Mooney RA. Interleukin-6
- Induces Cellular Insulin Resistance in Hepatocytes. Diabetes.
- ;51(12); 3391–3399.
- Rotter V, Nagaev I, Smith U. Interleukin-6 (IL-6) induces
- insulin resistance in 3T3-L1 adipocytes and is, like IL-8 and
- tumor necrosis factor-alpha, overexpressed in human fat cells
- from insulin-resistant subjects. The Journal of Biological
- Chemistry. 2003;278(46); 45777–45784.
- Nieto-Vazquez I, Fernandez-Veledo S, Kramer DK, Vila-
- Bedmar R, Garcia-Guerra L, Lorenzo M. Insulin resistance
- associated to obesity: the link TNF-alpha. Archives of
- Physiology and Biochemistry. 2008;114(3); 183–194.
- Kumar S, Pandey AK. Chemistry and biological activities of
- flavonoids: an overview. The Scientific World Journal.
- ;2013; 162750.
- Formica JV, Regelson W. Review of the biology of
- Quercetin and related bioflavonoids. Food and Chemical
- Toxicology. 1995;33(12); 1061–1080.
- Kelly GS. Quercetin. Monograph. Alternative Medicine
- Review. 2011;16(2); 172–194.
- Kanter M. Protective effects of thymoquinone on
- streptozotocin-induced diabetic nephropathy. Journal of
- Molecular Histology. 2009;40(2); 107–115.
- Akash, Muhammad Sajid Hamid, Rehman K, Chen S. Role
- of inflammatory mechanisms in pathogenesis of type 2
- diabetes mellitus. Journal of Cellular Biochemistry.
- ;114(3); 525–531.
- King GL. The role of inflammatory cytokines in diabetes
- and its complications. Journal of Periodontology. 2008;79(8
- Suppl); 1527–1534.
- Bottino R, Lemarchand P, Trucco M, Giannoukakis N. Gene-
- and cell-based therapeutics for type I diabetes mellitus.
- Gene Therapy. 2003;10(10); 875–889.
- Nicholas D, Odumosu O, Langridge, William H R.
- Autoantigen based vaccines for type 1 diabetes. Discovery
- Medicine. 2011;11(59); 293–301.
- Phillips JM, Parish NM, Raine T, Bland C, Sawyer Y, De La
- Peña, Hugo ve ark. Type 1 diabetes development requires
- both CD4+ and CD8+ T cells and can be reversed by nondepleting
- antibodies targeting both T cell populations. The
- Review of Diabetic Studies 2009;6(2); 97–103.
- Hamilton-Williams EE, Palmer SE, Charlton B, Slattery RM.
- Beta cell MHC class I is a late requirement for diabetes.
- Proceedings of the National Academy of Sciences.
- ;100(11); 6688–6693.
- Pinkse, Gabrielle G M, Tysma, Odette H M, Bergen, Cees A
- M, Kester, Michel G D, Ossendorp F, van Veelen, Peter A ve
- ark. Autoreactive CD8 T cells associated with beta cell
- destruction in type 1 diabetes. Proceedings of the National
- Academy of Sciences. 2005;102(51); 18425–18430.
- Wedrychowicz A, Dziatkowiak H, Sztefko K. Interleukin-6
- (IL-6) and IGF-IGFBP system in children and adolescents with
- type 1 diabetes mellitus. Experimental and Clinical
- Endocrinology & Diabetes. 2013;112(8); 435–439.
- Snell-Bergeon JK, West NA, Mayer-Davis EJ, Liese AD,
- Marcovina SM, D'Agostino, Ralph B Jr ve ark. Inflammatory
- markers are increased in youth with type 1 diabetes: the
- SEARCH Case-Control study. The Journal of Clinical
- Endocrinology & Metabolism. 2010;95(6); 2868–2876.
- Choi S, Choi K, Yoon I, Shin J, Kim J, Park W ve ark. IL-6
- protects pancreatic islet beta cells from pro-inflammatory
- cytokines-induced cell death and functional impairment in
- vitro and in vivo. Transplant Immunology. 2004;13(1); 43–53.
- Campbell IL, Hobbs MV, Dockter J, Oldstone MB, Allison J.
- Islet inflammation and hyperplasia induced by the pancreatic
- islet-specific overexpression of interleukin-6 in transgenic
- mice. American Journal of Pathology. 1994;145(1); 157–166.
- Wegner M, Araszkiewicz A, Piorunska-Stolzmann M,
- Wierusz-Wysocka B, Zozulinska-Ziolkiewicz D. Association
- Between IL-6 Concentration and Diabetes-Related Variables in
- DM1 Patients with and without Microvascular Complications.
- Inflammation. 2013;36(3); 723–728.
- Lee L, Xu B, Michie SA, Beilhack GF, Warganich T, Turley S
- ve ark. The role of TNF-alpha in the pathogenesis of type 1
- diabetes in the nonobese diabetic mouse: analysis of dendritic
- cell maturation. Proceedings of the National Academy of
- Sciences. 2005;102(44); 15995–16000.
- Koulmanda M, Bhasin M, Awdeh Z, Qipo A, Fan Z,
- Hanidziar D ve ark. The role of TNF-α in mice with type 1- and
- - diabetes. PLoS ONE. 2012;7(5); e33254.
- Garber AJ. Obesity and type 2 diabetes: which patients are
- at risk? Diabetes, Obesity and Metabolism. 2012;14(5); 399–
- -
- Yki-Järvinen H, Ryysy L, Kauppila M, Kujansuu E, Lahti J,
- Marjanen T ve ark. Effect of obesity on the response to insulin
- therapy in noninsulin-dependent diabetes mellitus. The
- Journal of Clinical Endocrinology & Metabolism. 1997;82(12);
- –4043.
- Cruz NG, Sousa LP, Sousa MO, Pietrani NT, Fernandes AP,
- Gomes KB. The linkage between inflammation and Type 2
- diabetes mellitus. Diabetes Research and Clinical Practice.
- ;99(2); 85–92.
- Zozulinska D, Wierusz-Wysocka B. Type 2 diabetes
- mellitus as inflammatory disease. Diabetes Research and
- Clinical Practice. 2006;74(2); S12.
- Rivera L, Morón R, Sánchez M, Zarzuelo A, Galisteo M.
- Quercetin ameliorates metabolic syndrome and improves the
- inflammatory status in obese Zucker rats. Obesity. 2008;16(9);
- –2087.
- Chuang C, Martinez K, Xie G, Kennedy A, Bumrungpert A,
- Overman A ve ark. Quercetin is equally or more effective than
- resveratrol in attenuating tumor necrosis factor- -mediated
- inflammation and insulin resistance in primary human
- adipocytes. American Journal of Clinical Nutrition. 2010;92(6);
- –1521.
- Zahedi M, Ghiasvand R, Feizi A, Asgari G, Darvish L. Does
- Quercetin Improve Cardiovascular Risk factors and
- Inflammatory Biomarkers in Women with Type 2 Diabetes: A
- Double-blind Randomized Controlled Clinical Trial.
- International Journal of Preventive Medicine. 2013;4(7); 777–
- -
- Egert S, Bosy-Westphal A, Seiberl J, Kürbitz C, Settler U,
- Plachta-Danielzik S ve ark. Quercetin reduces systolic blood
- pressure and plasma oxidised low-density lipoprotein
- concentrations in overweight subjects with a highcardiovascular
- disease risk phenotype: a double-blinded,
- placebo-controlled cross-over study. British Journal of
- Nutrition. 2009;102(7); 1065–1074.
- Manach C, Williamson G, Morand C, Scalbert A, Remesy C.
- Bioavailability and bioefficacy of polyphenols in humans. I.
- Review of 97 bioavailability studies. The American Journal of
- Clinical Nutrition. 2005;81(1 Suppl); 230S-242S.
- . 2011; 112 (6): 318-22.
- Noyan T, Balahoroğlu R, Kömüroğlu U. The Effects of Vitamin
- A, E, and C Combined Insulin Treatments on the
- Antioxidant Enzymes in the Diabetic Rats. Türk Klinik Biyokimya
- Derg. 2004; 2(3): 113-119.
Ayrıntılar
| Birincil Dil | Türkçe |
|---|---|
| Bölüm | Makaleler |
| Yazarlar | |
| Yayımlanma Tarihi | 16 Mayıs 2015 |
| Yayımlandığı Sayı | Yıl 2015 Cilt: 1 Sayı: 2 |