Curcumin Ameliorate Diabetes type 1 Complications through Decreasing Pro-inflammatory Cytokines in C57BL/6 Mice
Type 1 diabetes is a chronic autoimmune disease of beta cells in the islets of Langerhans, which are responsible for making insulin. Even with insulin therapy, inflammatory complications will develop in the long term.
The present study examines changes in serum levels of interleukin (IL)-6, IL-17, IL-10, tumor necrosis factor (TNF)-α, interferon (IFN)-γ, C-peptide, Insulin as well as fasting blood sugar (FBS) in control, diabetic and diabetic treated with curcumin groups. Thirty inbred C57BL /6 mice were randomly divided into three groups of 10 mice: group A consisted of healthy mice receiving citrate buffer, group B included a group of diabetic mice, and group C was a group of diabetic mice treated with curcumin. The cytokine levels were measured in the supernatant of stimulated splenocytes using enzyme -linked immunosorbent assay (ELISA). Radioimmunoassay was used to measure insulin and c-peptide levels. The FBS was measured by an automatic glucometer device.
The levels of IL-6, IL-17, and IFN-γ, as well as FBS, was significantly decreased in the treated group with curcumin compared to the diabetic group mice (p<0.05). TNF-α levels were also low, but the difference was not significant. IL-10, plasma C-peptide, and insulin significantly increased in the supernatant of stimulated splenocytes of treated diabetic group than in the diabetic group (p<0/05).
According to the results, this study supports the anti-diabetic and anti-inflammatory effects of curcumin; however, more studies are needed to investigate theeffects of curcumin and the dose-response relationship in this disease.
2. Bluestone JA, Herold K, Eisenbarth G. Genetics, pathogenesis and clinical interventions in type 1 diabetes. Nature. 2010;464(7293):1293–300.
3. Maahs DM, Rewers M. Mortality and renal disease in type 1 diabetes mellitus - Progress made, more to be done. J Clin Endocrinol Metab. 2006;91(10):3757–9.
4. Nathan DM. Sustained Effect of Intensive Treatment of Type 1 Diabetes Mellitus on Development and Progression of Diabetic Nephropathy: The Epidemiology of Diabetes Interventions and Complications (EDIC) Study. J Am Med Assoc. 2003;290(16):2159–67.
5. Rabinovitch A, Suarez-Pinzon WL. Cytokines and their roles in pancreatic islet β-cell destruction and insulin-dependent diabetes mellitus. Biochem Pharmacol.1998;55(8):1139–49.
6. Leslie RD. Predicting adult-onset autoimmune diabetes clarity from complexity. Diabetes. 2010;59(2):330–1.
7. Polonsky KS, Licinio-Paixao J, Given BD, Pugh W, Rue P, Galloway J, et al. Use of biosynthetic human C-peptide in the measurement of insulin secretion rates in normal volunteers and type I diabetic patients. J Clin Invest. 1986;77(1):98–105.
8. Jones AG, Hattersley AT. The clinical utility of C-peptide measurement in the care of patients with diabetes. Diabet Med. 2013;30(7):803–17.
9. Müller A, Schott-Ohly P, Dohle C, Gleichmann H. Differential regulation of Th1-type and Th2-type cytokine profiles in pancreatic islets of C57BL/6 and BALB/c mice by multiple low doses of streptozotocin. Immunobiology. 2002;205(1):35–50.
10. Ravindran J, Prasad S, Aggarwal BB. Curcumin and cancer cells: How many ways can curry kill tumor cells selectively? AAPS J. 2009;11(3):495–510.
11. Anand P, Thomas SG, Kunnumakkara AB, Sundaram C, Harikumar KB, Sung B, et al. Biological activities of curcumin and its analogues (Congeners) made by man and Mother Nature. Biochem Pharmacol. 2008;76(11):1590–611.
12. Dhillon N, Aggarwal BB, Newman RA, Wolff RA, Kunnumakkara AB, Abbruzzese JL, et al. Phase II trial of curcumin in patients with advanced pancreatic cancer. Clin Cancer Res. 2008;14(14):4491–9.
13. Anand P, Sundaram C, Jhurani S, Kunnumakkara AB, Aggarwal BB. Curcumin and cancer: An ‘old-age’ disease with an ‘age-old’ solution. Cancer Lett. 2008;267(1):133–64.
14. Anand, P., Kunnumakkara, AB, Newman, RA, y Aggarwal B. Biodisponibilidad de la curcumina: problemas y promesas. Farm Mol. 2007;4(6):807–18.
15. Sandur SK, Ichikawa H, Pandey MK, Kunnumakkara AB, Sung B, Sethi G, et al. Role of pro-oxidants and antioxidants in the anti-inflammatory and apoptotic effects of curcumin (diferuloylmethane). Free Radic Biol Med. 2007;43(4):568–80.
16. Faridi SH, Delirezh N, Abtahi Froushani SM. Beneficial Effects of Hydroalcoholic Extract of Saffron in Alleviating Experimental Autoimmune Diabetes in C57bl/6 Mice. Iran J Allergy Asthma Immunol. 2019;18(1):38-47.
17. Kalate Tanhaye Sabz F, Farokhi F, Delirezh N, Javadi S, Chapari H. In-vitro differentiation of rat peripheral blood monocytes into insulinproducing cells by rat pancreatic extract. Tehran Univ Med J. 1390;69(4):211–7.
18. Mosayebi G, Ghazavi A, Salehi H, Payani MA, Khazaei MR. Effect of sesame oil on the inhibition of experimental autoimmune encephalomyelitis in C57BL/6 mice. Pakistan J Biol Sci. 2007;10(11):1790–6.
19. Melloul D. Role of NF-kB in b-cell death. Biochem Soc Trans. 2008;36:334–9.
20. Langrish CL, Chen Y, Blumenschein WM, Mattson J, Basham B, Sedgwick JD, et al. IL-23 drives a pathogenic T cell population that induces autoimmune inflammation. J Exp Med. 2005;201(2): 233–40.
21. Pennline KJ, Roque-Gaffney E, Monahan M. Recombinant human IL-10 prevents the onset of diabetes in the nonobese diabetic mouse. Clin Immunol Immunopathol. 1994;71:169–175.
22. Miller AH, Raison CL. The role of inflammation in depression: from evolutionary imperative to modern treatment target. Nat Rev Immunol. 2016;16:22–34.
23. Kang BY, Chung SW, Chung W, Im S, Hwang SY, Kim TS. Inhibition of interleukin-12 production in lipopolysaccharide-activated macrophages by curcumin. Eur. J. Pharmacol. 1999; 38: 191–195.
24. Meghana K, Sanjeev G, Ramesh B. Curcumin prevents streptozotocin-induced islet damage by scavenging free radicals: A prophylactic and protective role. Eur J Pharmacol. 2007;577(1–3):183–91.
25. Abdel Aziz MT, El-Asmar MF, Rezq AM, Mahfouz SM,Wassef MA,Fouad HH,et al. The effect of a novel curcumin derivative on pancreatic islet regeneration in experimental type-1 diabetes in rats (long term study). Diabetol Metab Syndr. 2013;5(1):75.
26. Chougala MB, Bhaskar JJ, Rajan MGR, Salimath P V. Effect of curcumin and quercetin on lysosomal enzyme activities in streptozotocin-induced diabetic rats. Clin Nutr. 2012;31(5):749–55.
27. Murugan P, Pari L. Effect of tetrahydrocurcumin on lipid peroxidation and lipids in streptozotocin-nicotinamide-induced diabetic rats. Basic Clin Pharmacol Toxicol. 2006;99(2):122–7.
28. Pari L, Murugan P. Tetrahydrocurcumin prevents brain lipid peroxidation in streptozotocin-induced diabetic rats. J Med Food. 2007;10(2):323-9.
29. Zhang DW, Fu M, Gao SH, Liu JL. Curcumin and Diabetes: A Systematic Review. Evid Based Complement Alternat Med. 2013;2013:636053.
30. Kanitkar M,Gokhale K,Galande S,Bhonde RR. Novel role of curcumin in the prevention of cytokine-induced islet death in vitro and diabetogenesis in vivo. Br J Pharmacol. 2008;155(5):702-13.
31. Abdollahi E, Momtazi AA, Johnston TP, Sahebkar A. Therapeutic effects of curcumin in inflammatory and immune-mediated diseases: A nature-made jack-of-all-trades? J Cell Physiol. 2018;233(2):830-48.