Curcumin and Its Semisynthetic Derivative F-Curcumin Ameliorate the Expression of Cytokines in Autoimmune Encephalomyelitis Mouse Models of Multiple Sclerosis
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Abstract
Multiple sclerosis (MS) is an inflammatory disorder impacting the central nervous system, with cytokines significantly influencing its pathogenesis. This study investigates the effect of curcumin and its semisynthetic derivative F-curcumin on cytokine gene expression in autoimmune encephalomyelitis (EAE) mouse models of MS.
We assessed the expression levels of specific cytokines including interleukin (IL)-1β, IL-4, IL-10, IL-17, interferon-γ (IFN-γ), and transforming growth factor-β (TGF-β), alongside key transcription factors for helper T cells (T-bet, GATA-3, RORγt, and FoxP3) in both the spinal cord and spleen.
Treatment with curcumin and F-curcumin significantly ameliorated the severity and onset of EAE. Notably, mice administered with either compound showed a substantial decrease in the expression of genes encoding IL-1 (2 folds), IFN-γ (2 and 4 folds), and IL-17 (2.5 and 3.5 folds), alongside a marked increase in TGF-β (7 folds) and IL-10 (4 and 6 folds) levels. Additionally, the gene expression of T cell-derived transcription factors nearly mirrored the changes observed in pro-inflammatory and anti-inflammatory cytokines across the groups. The F-curcumin-treated group exhibited more pronounced results.
In conclusion, curcumin and F-curcumin significantly modulate cytokine gene expression during EAE induction, potentially alleviating inflammation in MS, with F-curcumin showing a more substantial effect.
1. Burrows DJ, McGown A, Jain SA, De Felice M, Ramesh TM, Sharrack B, et al. Animal models of multiple sclerosis: From rodents to zebrafish. Mult Scler. 2019;25(3):306-24.
2. Goldenberg MM. Multiple sclerosis review. P & T : a peer-reviewed journal for formulary management. 2012;37(3):175-84.
3. Bettelli E, Nicholson LB. The role of cytokines in experimental autoimmune encephalomyelitis. Arch Immunol Ther Exp (Warsz). 2000;48(5):389-98.
4. Constantinescu CS, Farooqi N, O'Brien K, Gran B. Experimental autoimmune encephalomyelitis (EAE) as a model for multiple sclerosis (MS). British J pharmacol. 2011;164(4):1079-106.
5. Wu GF, Alvarez E. The immunopathophysiology of multiple sclerosis. Neurol Clin. 2011;29(2):257-78.
6. Huang W-X, Huang P, Link H, Hillert J. Cytokine analysis in multiple sclerosis by competitive RT-PCR: a decreased expression of IL-10 and an increased expression of TNF-α in chronic progression. Mult Scler J. 1999;5(5):342-8.
7. van Boxel-Dezaire AH, Hoff SC, van Oosten BW, Verweij CL, Dräger AM, Adèr HJ, et al. Decreased interleukin-10 and increased interleukin-12p40 mRNA are associated with disease activity and characterize different disease stages in multiple sclerosis. Annals Neurolo. 1999;45(6):695-703.
8. Soleimani M, Jameie SB, Barati M, Mehdizadeh M, Kerdari M. Effects of coenzyme Q10 on the ratio of TH1/TH2 in experimental autoimmune encephalomyelitis model of multiple sclerosis in C57BL/6. Iran Biomed J. 2014;18(4):203-11.
9. Rostami A, Ciric B. Role of Th17 cells in the pathogenesis of CNS inflammatory demyelination. J Neurol Sci. 2013;333(1-2):76-87.
10. Sen MK, Almuslehi MSM, Shortland PJ, Coorssen JR, Mahns DA. Revisiting the Pathoetiology of Multiple Sclerosis: Has the Tail Been Wagging the Mouse? Front Immunol. 2020;11:572186.
11. McGeachy MJ, Stephens LA, Anderton SM. Natural recovery and protection from autoimmune encephalomyelitis: contribution of CD4+ CD25+ regulatory cells within the central nervous system. J Immunol. 2005;175(5):3025-32.
12. Hou H, Sun Y, Miao J, Gao M, Guo L, Song X. Ponesimod modulates the Th1/Th17/Treg cell balance and ameliorates disease in experimental autoimmune encephalomyelitis. J Neuroimmunol. 2021;356:577583.
13. Iarlori C, Gambi D, Lugaresi A, Patruno A, Felaco M, Salvatore M, et al. Reduction of free radicals in multiple sclerosis: effect of glatiramer acetate (Copaxone). Mult Scler. 2008;14(6):739-48.
14. Lee DH, Gold R, Linker RA. Mechanisms of oxidative damage in multiple sclerosis and neurodegenerative diseases: therapeutic modulation via fumaric acid esters. Int J Mol Sci. 2012;13(9):11783-803.
15. Aggarwal BB, Harikumar KB. Potential therapeutic effects of curcumin, the anti-inflammatory agent, against neurodegenerative, cardiovascular, pulmonary, metabolic, autoimmune and neoplastic diseases. Int J Biochem Cell Biol. 2009;41(1):40-59.
16. Kuptniratsaikul S, Promsang T, Kongrukgreatiyos K. The chula knot: a new sliding locking knot with a special property. Arthrosc Tech. 2014;3(4):e465-7.
17. Allegri P, Mastromarino A, Neri P. Management of chronic anterior uveitis relapses: efficacy of oral phospholipidic curcumin treatment. Long-term follow-up. Clin Ophthalmol (Auckland, NZ). 2010;4:1201-6.
18. Gupta SC, Patchva S, Aggarwal BB. Therapeutic roles of curcumin: lessons learned from clinical trials. The AAPS J. 2013;15(1):195-218.
19. Anand P, Kunnumakkara AB, Newman RA, Aggarwal BB. Bioavailability of curcumin: problems and promises. Mol Pharmaceutics. 2007;4(6):807-18.
20. Nelson KM, Dahlin JL, Bisson J, Graham J, Pauli GF, Walters MA. The essential medicinal chemistry of curcumin: miniperspective. J Med Chemistry. 2017;60(5):1620-37.
21. Zeraati M, Enayati M, Kafami L, Shahidi SH, Salari AA. Gut microbiota depletion from early adolescence alters adult immunological and neurobehavioral responses in a mouse model of multiple sclerosis. Neuropharmacol. 2019;157:107685.
22. Natarajan C, Bright JJ. Curcumin inhibits experimental allergic encephalomyelitis by blocking IL-12 signaling through Janus kinase-STAT pathway in T lymphocytes. J Immunol. 2002;168(12):6506-13.
23. Esmaeelzadeh M, Salehi P, Bararjanian M, Gharaghani S. Synthesis of new triazole tethered derivatives of curcumin and their antibacterial and antifungal properties. Journal of the Iranian Chemical Society. 2019;16(3):465-77.
24. Krishnaraju A, Sundararaju D, Sengupta K, Venkateswarlu S, Trimurtulu G. Safety and toxicological evaluation of demethylatedcurcuminoids; a novel standardized curcumin product. Toxicol Mechanisms Methods. 2009;19(6-7):447-60.
25. Dadhaniya P, Patel C, Muchhara J, Bhadja N, Mathuria N, Vachhani K, et al. Safety assessment of a solid lipid curcumin particle preparation: acute and subchronic toxicity studies. Food Chem Toxicol. 2011;49(8):1834-42.
26. Jantawong C, Priprem A, Intuyod K, Pairojkul C, Pinlaor P, Waraasawapati S, et al. Curcumin-loaded nanocomplexes: Acute and chronic toxicity studies in mice and hamsters. Toxicol Reports. 2021;8:1346-57.
27. Fu Y-S, Chen T-H, Weng L, Huang L, Lai D, Weng C-F. Pharmacological properties and underlying mechanisms of curcumin and prospects in medicinal potential. Biomed Pharm. 2021;141:111888.
28. Khaligh P, Salehi P, Bararjanian M, Aliahmadi A, Khavasi HR, Nejad-Ebrahimi S. Synthesis and in vitro antibacterial evaluation of novel 4-substituted 1-menthyl-1, 2, 3-triazoles. Chem Pharma Bull. 2016;64(11):1589-96.
29. Duan Y-C, Ma Y-C, Zhang E, Shi X-J, Wang M-M, Ye X-W, et al. Design and synthesis of novel 1, 2, 3-triazole-dithiocarbamate hybrids as potential anticancer agents. Europ J Med Chem. 2013;62:11-9.
30. Fu Y, Zheng S, Lin J, Ryerse J, Chen A. Curcumin protects the rat liver from CCl4-caused injury and fibrogenesis by attenuating oxidative stress and suppressing inflammation. Mol Pharmacol. 2008;73(2):399-409.
31. Motterlini R, Foresti R, Bassi R, Green CJ. Curcumin, an antioxidant and anti-inflammatory agent, induces heme oxygenase-1 and protects endothelial cells against oxidative stress. Free Radical Biol Med. 2000;28(8):1303-12.
32. Groom MJ, Lincoln NB, Francis VM, Stephan TF. Assessing mood in patients with multiple sclerosis. Clin Rehabilitation. 2003;17(8):847-57.
33. Haas J, Hug A, Viehöver A, Fritzsching B, Falk CS, Filser A, et al. Reduced suppressive effect of CD4+ CD25high regulatory T cells on the T cell immune response against myelin oligodendrocyte glycoprotein in patients with multiple sclerosis. Europ J immunol. 2005;35(11):3343-52.
34. Gaupp S, Cannella B, Raine CS. Amelioration of experimental autoimmune encephalomyelitis in IL-4Ralpha-/- mice implicates compensatory up-regulation of Th2-type cytokines. Am J Pathol. 2008;173(1):119-29.
35. Zhou Y, Zhang Y, Han J, Yang M, Zhu J, Jin T. Transitional B cells involved in autoimmunity and their impact on neuroimmunological diseases. J Translat Med. 2020;18(1):1-12.
36. Lewis SM, Williams A, Eisenbarth SC. Structure and function of the immune system in the spleen. Sci Immunol. 2019;4(33).
37. MARTÍN‐ARAGÓN S, Benedí JM, Villar AM. Modifications on antioxidant capacity and lipid peroxidation in mice under fraxetin treatment. J Pharmecy Pharmacol. 1997;49(1):49-52.
38. Li W, Suwanwela NC, Patumraj S. Curcumin by down-regulating NF-kB and elevating Nrf2, reduces brain edema and neurological dysfunction after cerebral I/R. Microvascular Res. 2016;106:117-27.
39. Bright JJ. Curcumin and autoimmune disease. Adv Exp Med Biol. 2007:425-51.
40. Momtazi-Borojeni AA, Haftcheshmeh SM, Esmaeili S-A, Johnston TP, Abdollahi E, Sahebkar A. Curcumin: A natural modulator of immune cells in systemic lupus erythematosus. Autoimmunity Rev. 2018;17(2):125-35.
41. Xie L, Li X-K, Funeshima-Fuji N, Kimura H, Matsumoto Y, Isaka Y, et al. Amelioration of experimental autoimmune encephalomyelitis by curcumin treatment through inhibition of IL-17 production. Int Immunopharmacol. 2009;9(5):575-81.
42. Waisman A, Hauptmann J, Regen T. The role of IL-17 in CNS diseases. Acta neuropathologica. 2015;129(5):625-37.
43. Harris TJ, Grosso JF, Yen H-R, Xin H, Kortylewski M, Albesiano E, et al. Cutting edge: An in vivo requirement for STAT3 signaling in TH17 development and TH17-dependent autoimmunity. J Immunol. 2007;179(7):4313-7.
44. Ifergan I, Kebir H, Bernard M, Wosik K, Dodelet-Devillers A, Cayrol R, et al. The blood–brain barrier induces differentiation of migrating monocytes into Th17-polarizing dendritic cells. Brain. 2008;131(3):785-99.
45. Xie L, Li X-K, Takahara S. Curcumin has bright prospects for the treatment of multiple sclerosis. Int Immunopharmacol. 2011;11(3):323-30.
46. Gocke AR, Cravens PD, Ben L-H, Hussain RZ, Northrop SC, Racke MK, et al. T-bet regulates the fate of Th1 and Th17 lymphocytes in autoimmunity. J Immunol. 2007;178(3):1341-8.
47. Kanakasabai S, Casalini E, Walline CC, Mo C, Chearwae W, Bright JJ. Differential regulation of CD4+ T helper cell responses by curcumin in experimental autoimmune encephalomyelitis. J Nutr Biochem. 2012;23(11):1498-507.
48. Scazzone C, Agnello L, Lo Sasso B, Salemi G, Gambino CM, Ragonese P, et al. Foxp3 and gata3 polymorphisms, vitamin d3 and multiple sclerosis. Brain Sci. 2021;11(4):415.
49. Fernando V, Omura S, Sato F, Kawai E, Martinez NE, Elliott SF, et al. Regulation of an autoimmune model for multiple sclerosis in Th2-biased GATA3 transgenic mice. Int J Mol Sci. 2014;15(2):1700-18.
50. Tabares-Guevara JH, Jaramillo JC, Ospina-Quintero L, Piedrahíta-Ochoa CA, García-Valencia N, Bautista-Erazo DE, et al. IL-10-Dependent Amelioration of Chronic Inflammatory Disease by Microdose Subcutaneous Delivery of a Prototypic Immunoregulatory Small Molecule. Front Immunol. 2021;12.
2. Goldenberg MM. Multiple sclerosis review. P & T : a peer-reviewed journal for formulary management. 2012;37(3):175-84.
3. Bettelli E, Nicholson LB. The role of cytokines in experimental autoimmune encephalomyelitis. Arch Immunol Ther Exp (Warsz). 2000;48(5):389-98.
4. Constantinescu CS, Farooqi N, O'Brien K, Gran B. Experimental autoimmune encephalomyelitis (EAE) as a model for multiple sclerosis (MS). British J pharmacol. 2011;164(4):1079-106.
5. Wu GF, Alvarez E. The immunopathophysiology of multiple sclerosis. Neurol Clin. 2011;29(2):257-78.
6. Huang W-X, Huang P, Link H, Hillert J. Cytokine analysis in multiple sclerosis by competitive RT-PCR: a decreased expression of IL-10 and an increased expression of TNF-α in chronic progression. Mult Scler J. 1999;5(5):342-8.
7. van Boxel-Dezaire AH, Hoff SC, van Oosten BW, Verweij CL, Dräger AM, Adèr HJ, et al. Decreased interleukin-10 and increased interleukin-12p40 mRNA are associated with disease activity and characterize different disease stages in multiple sclerosis. Annals Neurolo. 1999;45(6):695-703.
8. Soleimani M, Jameie SB, Barati M, Mehdizadeh M, Kerdari M. Effects of coenzyme Q10 on the ratio of TH1/TH2 in experimental autoimmune encephalomyelitis model of multiple sclerosis in C57BL/6. Iran Biomed J. 2014;18(4):203-11.
9. Rostami A, Ciric B. Role of Th17 cells in the pathogenesis of CNS inflammatory demyelination. J Neurol Sci. 2013;333(1-2):76-87.
10. Sen MK, Almuslehi MSM, Shortland PJ, Coorssen JR, Mahns DA. Revisiting the Pathoetiology of Multiple Sclerosis: Has the Tail Been Wagging the Mouse? Front Immunol. 2020;11:572186.
11. McGeachy MJ, Stephens LA, Anderton SM. Natural recovery and protection from autoimmune encephalomyelitis: contribution of CD4+ CD25+ regulatory cells within the central nervous system. J Immunol. 2005;175(5):3025-32.
12. Hou H, Sun Y, Miao J, Gao M, Guo L, Song X. Ponesimod modulates the Th1/Th17/Treg cell balance and ameliorates disease in experimental autoimmune encephalomyelitis. J Neuroimmunol. 2021;356:577583.
13. Iarlori C, Gambi D, Lugaresi A, Patruno A, Felaco M, Salvatore M, et al. Reduction of free radicals in multiple sclerosis: effect of glatiramer acetate (Copaxone). Mult Scler. 2008;14(6):739-48.
14. Lee DH, Gold R, Linker RA. Mechanisms of oxidative damage in multiple sclerosis and neurodegenerative diseases: therapeutic modulation via fumaric acid esters. Int J Mol Sci. 2012;13(9):11783-803.
15. Aggarwal BB, Harikumar KB. Potential therapeutic effects of curcumin, the anti-inflammatory agent, against neurodegenerative, cardiovascular, pulmonary, metabolic, autoimmune and neoplastic diseases. Int J Biochem Cell Biol. 2009;41(1):40-59.
16. Kuptniratsaikul S, Promsang T, Kongrukgreatiyos K. The chula knot: a new sliding locking knot with a special property. Arthrosc Tech. 2014;3(4):e465-7.
17. Allegri P, Mastromarino A, Neri P. Management of chronic anterior uveitis relapses: efficacy of oral phospholipidic curcumin treatment. Long-term follow-up. Clin Ophthalmol (Auckland, NZ). 2010;4:1201-6.
18. Gupta SC, Patchva S, Aggarwal BB. Therapeutic roles of curcumin: lessons learned from clinical trials. The AAPS J. 2013;15(1):195-218.
19. Anand P, Kunnumakkara AB, Newman RA, Aggarwal BB. Bioavailability of curcumin: problems and promises. Mol Pharmaceutics. 2007;4(6):807-18.
20. Nelson KM, Dahlin JL, Bisson J, Graham J, Pauli GF, Walters MA. The essential medicinal chemistry of curcumin: miniperspective. J Med Chemistry. 2017;60(5):1620-37.
21. Zeraati M, Enayati M, Kafami L, Shahidi SH, Salari AA. Gut microbiota depletion from early adolescence alters adult immunological and neurobehavioral responses in a mouse model of multiple sclerosis. Neuropharmacol. 2019;157:107685.
22. Natarajan C, Bright JJ. Curcumin inhibits experimental allergic encephalomyelitis by blocking IL-12 signaling through Janus kinase-STAT pathway in T lymphocytes. J Immunol. 2002;168(12):6506-13.
23. Esmaeelzadeh M, Salehi P, Bararjanian M, Gharaghani S. Synthesis of new triazole tethered derivatives of curcumin and their antibacterial and antifungal properties. Journal of the Iranian Chemical Society. 2019;16(3):465-77.
24. Krishnaraju A, Sundararaju D, Sengupta K, Venkateswarlu S, Trimurtulu G. Safety and toxicological evaluation of demethylatedcurcuminoids; a novel standardized curcumin product. Toxicol Mechanisms Methods. 2009;19(6-7):447-60.
25. Dadhaniya P, Patel C, Muchhara J, Bhadja N, Mathuria N, Vachhani K, et al. Safety assessment of a solid lipid curcumin particle preparation: acute and subchronic toxicity studies. Food Chem Toxicol. 2011;49(8):1834-42.
26. Jantawong C, Priprem A, Intuyod K, Pairojkul C, Pinlaor P, Waraasawapati S, et al. Curcumin-loaded nanocomplexes: Acute and chronic toxicity studies in mice and hamsters. Toxicol Reports. 2021;8:1346-57.
27. Fu Y-S, Chen T-H, Weng L, Huang L, Lai D, Weng C-F. Pharmacological properties and underlying mechanisms of curcumin and prospects in medicinal potential. Biomed Pharm. 2021;141:111888.
28. Khaligh P, Salehi P, Bararjanian M, Aliahmadi A, Khavasi HR, Nejad-Ebrahimi S. Synthesis and in vitro antibacterial evaluation of novel 4-substituted 1-menthyl-1, 2, 3-triazoles. Chem Pharma Bull. 2016;64(11):1589-96.
29. Duan Y-C, Ma Y-C, Zhang E, Shi X-J, Wang M-M, Ye X-W, et al. Design and synthesis of novel 1, 2, 3-triazole-dithiocarbamate hybrids as potential anticancer agents. Europ J Med Chem. 2013;62:11-9.
30. Fu Y, Zheng S, Lin J, Ryerse J, Chen A. Curcumin protects the rat liver from CCl4-caused injury and fibrogenesis by attenuating oxidative stress and suppressing inflammation. Mol Pharmacol. 2008;73(2):399-409.
31. Motterlini R, Foresti R, Bassi R, Green CJ. Curcumin, an antioxidant and anti-inflammatory agent, induces heme oxygenase-1 and protects endothelial cells against oxidative stress. Free Radical Biol Med. 2000;28(8):1303-12.
32. Groom MJ, Lincoln NB, Francis VM, Stephan TF. Assessing mood in patients with multiple sclerosis. Clin Rehabilitation. 2003;17(8):847-57.
33. Haas J, Hug A, Viehöver A, Fritzsching B, Falk CS, Filser A, et al. Reduced suppressive effect of CD4+ CD25high regulatory T cells on the T cell immune response against myelin oligodendrocyte glycoprotein in patients with multiple sclerosis. Europ J immunol. 2005;35(11):3343-52.
34. Gaupp S, Cannella B, Raine CS. Amelioration of experimental autoimmune encephalomyelitis in IL-4Ralpha-/- mice implicates compensatory up-regulation of Th2-type cytokines. Am J Pathol. 2008;173(1):119-29.
35. Zhou Y, Zhang Y, Han J, Yang M, Zhu J, Jin T. Transitional B cells involved in autoimmunity and their impact on neuroimmunological diseases. J Translat Med. 2020;18(1):1-12.
36. Lewis SM, Williams A, Eisenbarth SC. Structure and function of the immune system in the spleen. Sci Immunol. 2019;4(33).
37. MARTÍN‐ARAGÓN S, Benedí JM, Villar AM. Modifications on antioxidant capacity and lipid peroxidation in mice under fraxetin treatment. J Pharmecy Pharmacol. 1997;49(1):49-52.
38. Li W, Suwanwela NC, Patumraj S. Curcumin by down-regulating NF-kB and elevating Nrf2, reduces brain edema and neurological dysfunction after cerebral I/R. Microvascular Res. 2016;106:117-27.
39. Bright JJ. Curcumin and autoimmune disease. Adv Exp Med Biol. 2007:425-51.
40. Momtazi-Borojeni AA, Haftcheshmeh SM, Esmaeili S-A, Johnston TP, Abdollahi E, Sahebkar A. Curcumin: A natural modulator of immune cells in systemic lupus erythematosus. Autoimmunity Rev. 2018;17(2):125-35.
41. Xie L, Li X-K, Funeshima-Fuji N, Kimura H, Matsumoto Y, Isaka Y, et al. Amelioration of experimental autoimmune encephalomyelitis by curcumin treatment through inhibition of IL-17 production. Int Immunopharmacol. 2009;9(5):575-81.
42. Waisman A, Hauptmann J, Regen T. The role of IL-17 in CNS diseases. Acta neuropathologica. 2015;129(5):625-37.
43. Harris TJ, Grosso JF, Yen H-R, Xin H, Kortylewski M, Albesiano E, et al. Cutting edge: An in vivo requirement for STAT3 signaling in TH17 development and TH17-dependent autoimmunity. J Immunol. 2007;179(7):4313-7.
44. Ifergan I, Kebir H, Bernard M, Wosik K, Dodelet-Devillers A, Cayrol R, et al. The blood–brain barrier induces differentiation of migrating monocytes into Th17-polarizing dendritic cells. Brain. 2008;131(3):785-99.
45. Xie L, Li X-K, Takahara S. Curcumin has bright prospects for the treatment of multiple sclerosis. Int Immunopharmacol. 2011;11(3):323-30.
46. Gocke AR, Cravens PD, Ben L-H, Hussain RZ, Northrop SC, Racke MK, et al. T-bet regulates the fate of Th1 and Th17 lymphocytes in autoimmunity. J Immunol. 2007;178(3):1341-8.
47. Kanakasabai S, Casalini E, Walline CC, Mo C, Chearwae W, Bright JJ. Differential regulation of CD4+ T helper cell responses by curcumin in experimental autoimmune encephalomyelitis. J Nutr Biochem. 2012;23(11):1498-507.
48. Scazzone C, Agnello L, Lo Sasso B, Salemi G, Gambino CM, Ragonese P, et al. Foxp3 and gata3 polymorphisms, vitamin d3 and multiple sclerosis. Brain Sci. 2021;11(4):415.
49. Fernando V, Omura S, Sato F, Kawai E, Martinez NE, Elliott SF, et al. Regulation of an autoimmune model for multiple sclerosis in Th2-biased GATA3 transgenic mice. Int J Mol Sci. 2014;15(2):1700-18.
50. Tabares-Guevara JH, Jaramillo JC, Ospina-Quintero L, Piedrahíta-Ochoa CA, García-Valencia N, Bautista-Erazo DE, et al. IL-10-Dependent Amelioration of Chronic Inflammatory Disease by Microdose Subcutaneous Delivery of a Prototypic Immunoregulatory Small Molecule. Front Immunol. 2021;12.
| Files | ||
| Issue | Vol 22 No 6 (2023) | |
| Section | Original Article(s) | |
| DOI | https://doi.org/10.18502/ijaai.v22i6.14646 | |
| Keywords | ||
| Autoimmune encephalomyelitis Curcumin; Inflammation Multiple sclerosis | ||
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How to Cite
1.
Khosropour S, Shahvarooghi E, Rezaeizadeh H, Esmaeelzadeh M. Curcumin and Its Semisynthetic Derivative F-Curcumin Ameliorate the Expression of Cytokines in Autoimmune Encephalomyelitis Mouse Models of Multiple Sclerosis. Iran J Allergy Asthma Immunol. 2023;22(6):575-587.
