sdü tıp fak derg

Medical Journal of Süleyman Demirel University

2602-2109

Süleyman Demirel Üniversitesi

10.17343/sdutfd.1330810

Neurology and Neuromuscular Diseases Traditional, Complementary and Integrative Medicine (Other)

Nöroloji ve Nöromüsküler Hastalıklar Geleneksel, Tamamlayıcı ve Bütünleştirici Tıp (Diğer)

The Efficacy of Some Herbal Therapies Preferred by Turkish MS Patients

Türk MS hastalarının tercih ettiği bazı bitkisel tedavilerin etkinliği

https://orcid.org/0000-0003-1561-1296

Demirci

Serpil

SÜLEYMAN DEMİREL ÜNİVERSİTESİ, TIP FAKÜLTESİ

https://orcid.org/0000-0002-4424-044X

Doğan Ünlü

Melike

SÜLEYMAN DEMİREL ÜNİVERSİTESİ, TIP FAKÜLTESİ

06 29 2024

31 2 195 204 07 21 2023 04 15 2024

1994

Süleyman Demirel Üniversitesi Tıp Fakültesi Dergisi

Multiple sclerosis (MS), that is the most common non-traumatic cause of disability among young adults, is a chronic, progressive, inflammatory and neurodegenerative disease of the central nervous system. Despite recent remarkable advances in treatment, there is no cure for MS. Many unmet needs of persons with MS encourages them to use complementary and alternative medicines, especially herbal medicines, as a promising therapeutic option. Here, potential benefits and mechanisms of action of some herbal medicines preferred by Turkish MS patients are reviewed.

Genç erişkinlerde en sık non-travmatik özürlülük nedeni olan multipl skleroz (MS), merkezi sinir sisteminin kronik, ilerleyici, inflamatuar ve nörodejeneratif bir hastalığıdır. Tedavide son zamanlardaki dikkate değer gelişmelere rağmen, MS'in kesin bir tedavisi yoktur. MS'li kişilerin karşılanmamış birçok ihtiyacı, umut verici bir terapötik seçenek olarak onları tamamlayıcı ve alternatif ilaçlar, özellikle bitkisel ilaçlar kullanmaya teşvik eder. Burada Türk MS hastalarının tercih ettiği bazı bitkisel ilaçların potansiyel faydaları ve etki mekanizmaları gözden geçirilmiştir.

herbal therapy multiple sclerosis medicinal plants

herbal terapi multipl skleroz tıbbi bitkiler

yok

1. Dendrou CA, Fugger L, Friese MA. Immunopathology of Multiple Sclerosis. Nat Rev Immunol 2015 Sep 15;15(9):545-58. doi: 10.1038/nri3871.

2. Haase S, Linker RA. Inflammation in Multiple Sclerosis. Ther Adv Neurol Disord 2021;14:17562864211007687. doi: 10.1177/17562864211007687.

3. Kunkl M, Frascolla S, Amormino C, Volpe E, Tuosto L. T Helper Cells: the Modulators of Inflammation in Multiple Cclerosis Cells 2020;9(2):482. doi: 10.3390/cells9020482.

4. Ivanova EA, Orekhov AN. T Helper Lymphocyte Subsets and Plasticity in Autoimmunity and Cancer: An Overview. Biomed Res Int 2015;2015:327470. doi: 10.1155/2015/327470.

5. Tangkiatkumjai M, Boardman H, Walker DM. Potential Factors that Influence Usage of Complementary and Alternative Medicine Worldwide: A Systematic Review. BMC Complement Med Ther 2020;20(1):363. doi: 10.1186/s12906-020-03157-2.

6. Yadav V, Bever C Jr, Bowen J, Bowling A, Weinstock-Guttman B, Cameron M, Bourdette D, Gronseth GS, Narayanaswami P. Summary of Evidence-Based Guideline: Complementary and Alternative Medicine in Multiple Sclerosis: Report of the Guideline Development Subcommittee of the American Academy of Neurology. Neurology 2014;82(12):1083-92. doi: 10.1212/WNL.0000000000000250.

7. Pucci E, Cartechini E, Taus C, Giuliani G. Why Physicians Need to Look More Closely at the use of Complementary and Alternative Medicine by Multiple Sclerosis Patients. Eur J Neurol 2004;11(4):263-7. doi: 10.1046/j.1468-1331.2003.00758.x.

8. Gedizlioğlu M, Yumurtaş S, Trakyalı AU, Yıldırım F, Ortan P, Köşkderelioğlu A. Complementary and Alternative Therapy Use in Multiple Sclerosis: A Cross-Sectional Survey. Turk J Neurol 2015; 21(1): 13-15. Doi:10.4274/tnd.46354

9. Duru Aşiret G, Düğer Ü, Kapucu S, Tuncer Kurne A, Karabudak R. Multiple Skleroz Hastalarının Tamamlayıcı ve Alternatif Tedavi Kullanım Durumlarının Belirlenmesi. Gümüşhane Üniversitesi Sağlık Bilimleri Dergisi 2017;6:1-6.

10. Çelik RGG, Öztürk M, Altın S, Köseoğlu M, Sariahmetoğlu H, Tütüncü M, et al. The Prevalence of Alternative-Complementary Therapies in Patients with Multiple Sclerosis. Turk J Neurol 2019; 25(3): 153-58. doi: 10.4274/tnd.2019.04207

11. Dağlı S, Ünlü MD, Demirci S. Complementary and alternative medicine use in Multiple Sclerosis. 2nd International Turkic World Congress of Multiple Sclerosis 2020 Abstract Book, pp: 31.

12. Aksoy S, Şengül Y, Karaman HIÖ. Multipl Skleroz Hastalarına Tamamlayıcı ve Alternatif Tıp Yöntemlerine Başvurunun Demografik ve Klinik Korelasyonlarının Değerlendirilmesi. 2nd International Turkic World Congress of Multiple Sclerosis 2020 Abstract Book, pp: 16-17.

13. Dayapoğlu N, Tan M. Use of Complementary and Alternative Medicine Among People with Multiple Sclerosis in Eastern Turkey. Neurology Asia 2016; 21(1): 63-71.

14. Wink M. Modes of Action of Herbal Medicines and Plant Secondary Metabolites. Medicines (Basel) 2015;2(3):251-86. doi: 10.3390/medicines2030251.

15. Gazioglu I, Semen S, Acar OO, Kolak U, Sen A, Topcu G. Triterpenoids and Steroids Isolated from Anatolian Capparis Ovata and Their Activity on the Expression of Inflammatory Cytokines. Pharm Biol 2020;58(1):925-31. doi: 10.1080/13880209.2020.1814356.

16. Moutia M, El Azhary K, Elouaddari A, Al Jahid A, Jamal Eddine J, Seghrouchni F, et al. Capparis Spinosa L. Promotes Anti-Inflammatory Response In Vitro Through the Control of Cytokine Gene Expression in Human Peripheral Blood Mononuclear Cells. BMC Immunol 2016;17(1):26. doi: 10.1186/s12865-016-0164-x.

17. Ozgun-Acar O, Celik-Turgut G, Gazioglu I, Kolak U, Ozbal S, Ergur BU, et al. Capparis Ovata Treatment Suppresses Inflammatory Cytokine Expression and Ameliorates Experimental Allergic Encephalomyelitis Model of Multiple Sclerosis in C57BL/6 Mice. J Neuroimmunol 2016;298:106-16. doi: 10.1016/j.jneuroim.2016.07.010.

18. Ozgun-Acar O, Gazioglu I, Kolak U, Sen A, Topcu G. A Potential Therapeutic Role in Multiple Sclerosis for Stigmast-5,22-Dien-3b-ol Myristate Isolated from Capparis Ovata. Eurobiotech J 2017;1(3):241-46.

19. Sen A, Topcu G, Ozgun O, Kolak U, Hacibekiroglu I, Celik G, et al. Anti-Neuroinflammatory Effect of Butanolic Fraction of Capparis Ovata Water Extract Used as an Alternative and Complementary Treatment for Multiple Sclerosis. J Neuroimmunol 2014;275(1-2):172-73.

20. Choi JG, Kim SY, Jeong M, Oh MS. Pharmacotherapeutic Potential of Ginger and its Compounds in Age-Related Neurological Disorders. Pharmacol Ther 2018;182:56-69. doi: 10.1016/j.pharmthera.2017.08.010.

21. Mao QQ, Xu XY, Cao SY, Gan RY, Corke H, Beta T, et al. Bioactive Compounds and Bioactivities of Ginger (Zingiber Officinale Roscoe). Foods 2019;8(6):185. doi: 10.3390/foods8060185.

22. Jafarzadeh A, Nemati M. Therapeutic Potentials of Ginger for Treatment of Multiple Sclerosis: A Review with Emphasis on its Immunomodulatory, Anti-Inflammatory and Anti-Oxidative Properties. J Neuroimmunol 2018;324:54-75. doi: 10.1016/ j.jneuroim.2018.09.003.

23. Han JJ, Li X, Ye ZQ, Lu XY, Yang T, Tian J, et al. Treatment with 6-Gingerol Regulates Dendritic Cell Activity and Ameliorates the Severity of Experimental Autoimmune Encephalomyelitis. Mol Nutr Food Res 2019;63(18):e1801356. doi: 10.1002/mnfr.201801356

24. Jafarzadeh A, Mohammadi-Kordkhayli M, Ahangar-Parvin R, Azizi V, Khoramdel-Azad H, Shamsizadeh A, et al. Ginger Extracts Influence the Expression of IL27 and IL-33 in the Central Nervous System in Experimental Autoimmune Encephalomyelitis and Ameliorates the Clinical Symptoms of Disease. J Neuroimmunol 2014;276(1-2):80-8. doi: 10.1016/ j.jneuroim.2014.08.614.

25. Ho SC, Chang KS, Lin CC. Anti-Neuroinflammatory Capacity of Fresh Ginger is Attributed Mainly to 10-Gingerol. Food Chem 2013;141(3):3183-91. doi: 10.1016/j.foodchem.2013.06.010.

26. Shang A, Cao SY, Xu XY, Gan RY, Tang GY, Corke H, et al. Bioactive Compounds and Biological Functions of Garlic (Allium sativum L.). Foods 2019;8(7):246. doi: 10.3390/foods8070246.

27. Zeinali H, Baluchnejadmojarad T, Fallah S, Sedighi M, Moradi N, Roghani M. S-allyl Cysteine Improves Clinical and Neuropathological Features of Experimental Autoimmune Encephalomyelitis in C57BL/6 Mice. Biomed Pharmacother 2018;97:557-63. doi: 10.1016/j.biopha.2017.10.155.

28. Song H, Cui J, Mossine VV, Greenlief CM, Fritsche K, Sun GY, et al. Bioactive Components from Garlic on Brain Resiliency Against Neuroinflammation and Neurodegeneration. Exp Ther Med 2020;19(2):1554-59. doi: 10.3892/etm.2019.8389.

29. Abdullah A, Maged M, Hairul-Islam M I, Osama I A, Maha H, Manal A, et al. Activation of Aryl Hydrocarbon Receptor Signaling by a Novel Agonist Ameliorates Autoimmune Encephalomyelitis. PLoS One 2019;14(4):e0215981. doi: 10.1371/journal.pone.0215981.

30. Sıcak Y, Erdoğan Eliuz EA. Chemical Content and Biological Activity Spectrum of Nigella Sativa Seed Oil. KSU J Agric Nat 2019;22(5):928-34. doi: 10.18016/ksutarimdoga.vi.537674.

31. Dalli M, Bekkouch O, Azizi SE, Azghar A, Gseyra N, Kim B. Nigella sativa L. Phytochemistry and Pharmacological Activities: A Review (2019-2021). Biomolecules 2021;12(1):20. doi: 10.3390/biom12010020.

32. Majdalawieh AF, Fayyad MW. Immunomodulatory and Anti-Inflammatory Action of Nigella Sativa and Thymoquinone: A Comprehensive Review. Int Immunopharmacol 2015;28(1):295-304. doi: 10.1016/j.intimp.2015.06.023

33. Ali MY, Akter Z, Mei Z, Zheng M, Tania M, Khan MA. Thymoquinone in Autoimmune Diseases: Therapeutic Potential and Molecular Mechanisms. Biomed Pharmacother 2021;134:111157. doi: 10.1016/j.biopha.2020.111157

34. Wang Y, Gao H, Zhang W, Zhang W, Fang L. Thymoquinone Inhibits Lipopolysaccharide-Induced Inflammatory Mediators in BV2 Microglial Cells. Int Immunopharmacol 2015;26(1):169-173. doi: 10.1016/j.intimp.2015.03.013

35. Velagapudi R, Kumar A, Bhatia HS, El-Bakoush A, Lepiarz I, Fiebich BL, et al. Inhibition of Neuroinflammation by Thymoquinone Requires Activation of Nrf2/ARE Signalling. Int Immunopharmacol 2017;48:17-29. doi: 10.1016/j.intimp.2017.04.018

36. Taka E, Mazzio EA, Goodman CB, Redmon N, Flores-Rozas H, Reams R, et al. Anti-Inflammatory Effects of Thymoquinone in Activated BV-2 Microglial Cells. J Neuroimmunol 2015;286:5-12. doi: 10.1016/j.jneuroim.2015.06.011

37. Fahmy HM, Noor NA, Mohammed FF, Elsayed AA, Radwan NM. Nigella Sativa as an Anti-Inflammatory and Promising Remyelinating Agent in the Cortex and Hippocampus of Experimental Autoimmune Encephalomyelitis-Induced Rats. J Basic Appl Zool 2014;67(5):182-95. doi:10.1016/j.jobaz.2014.08.005.

38. Mohamed A, Afridi DM, Garani O, Tucci M. Thymoquinone Inhibits the Activation of NF-KappaB in the Brain and Spinal Cord of Experimental Autoimmune Encephalomyelitis. Biomed Sci Instrum 2005;41:388-93.

39. Noor NA, Fahmy HM, Mohammed FF, Elsayed AA, Radwan NM. Nigella Sativa Amliorates Inflammation and Demyelination in the Experimental Autoimmune Encephalomyelitis-Induced Wistar Rats. Int J Clin Exp Pathol 2015;8(6):6269-86.

40. Yüzbaşıoğlu İS. Oenothera Parodiana (Onagraceae): A New Alien Species Record for the Flora of Turkey. Biological Diversity and Conservation 2014;7(2):122-126.

41. Timoszuk M, Bielawska K, Skrzydlewska E. Evening Primrose (Oenothera Biennis) Biological Activity Dependent on Chemical Composition. Antioxidants (Basel) 2018;7(8):108. doi: 10.3390/antiox7080108.

42. Farzaei MH, Shahpiri Z, Bahramsoltani R, Nia MM, Najafi F, Rahimi R. Efficacy and Tolerability of Phytomedicines in Multiple Sclerosis Patients: A Review. CNS Drugs 2017;31(10):867-89. doi: 10.1007/s40263-017-0466-4.

43. Kapoor R, Huang YS. Gamma Linolenic Acid: An Antiinflammatory Omega-6 Fatty Acid. Curr Pharm Biotechnol 2006;7(6):531-4. doi: 10.2174/138920106779116874.

44. Cao D, Luo J, Zang W, Chen D, Xu H, Shi H, Jing X. Gamma-Linolenic Acid Suppresses NFκβ Signaling Via CD36 in the Lipopolysaccharide-Induced Inflammatory Response in Primary Goat Mammary Gland Epithelial Cells. Inflammation 2016;39(3):1225-37. doi: 10.1007/s10753-016-0358-7.

45. Rezapour-Firouzi S, Kheradmand F, Shahabi S, Tehrani AA, Mazloomi E, Mohammadzadeh A. Regulatory Effects of Hemp Seed/Evening Primrose Oil Supplement in Comparison With Rapamycin on the Expression of the Mammalian Target of Rapamycin-Complex 2 and Interleukin-10 Genes in Experimental Autoimmune Encephalomyelitis. Res Pharm Sci 2019;14(1):36-45. doi: 10.4103/1735-5362.251851.

46. Rezapour-Firouzi S, Mohammadian M, Sadeghzadeh M, Mehranfar S, Mazloomi E. The Effects of Evening Primrose/Hemp Seed Oil Compared to Rapamycin on the Gene Expression of Immunological Parameters in Experimental Autoimmune Encephalomyelitis Splenocytes. Iran J Allergy Asthma Immunol 2020;19(2):183-92. doi: 10.18502/ijaai.v19i2.2771.

47. Rezapour-Firouzi S, Arefhosseini SR, Mehdi F, Mehrangiz EM, Baradaran B, Sadeghihokmabad E, et al. Immunomodulatory and Therapeutic Effects of Hot-Nature Diet and Co-Supplemented Hemp Seed, Evening Primrose Oils Intervention in Multiple Sclerosis Patients. Complement Ther Med 2013;21(5):473-80. doi: 10.1016/j.ctim.2013.06.006.

48. Majdinasab N, Namjoyan F, Taghizadeh M, Saki H. The Effect of Evening Primrose Oil on Fatigue and Quality of Life in Patients with Multiple Sclerosis. Neuropsychiatr Dis Treat 2018;14:1505-12. doi: 10.2147/NDT.S149403.

49. Goyal A, Sharma V, Upadhyay N, Gill S, Sihag M. Flax and Flaxseed Oil: An Ancient Medicine & Modern Functional Food. J Food Sci Technol 2014;51(9):1633-53. doi: 10.1007/s13197-013-1247-9.

50. Rafieian-Kopaei M, Shakiba A, Sedighi M, Bahmani M. The Analgesic and Anti-Inflammatory Activity of Linum usitatissimum in Balb/c Mice. J Evid Based Complementary Altern Med 2017;22(4):892-96. doi: 10.1177/2156587217717416.

51. Chera EI, Pop RM, Pârvu M, Sorițău O, Uifălean A, Cătoi FA, et al. Flaxseed Ethanol Extracts' Antitumor, Antioxidant, and Anti-Inflammatory Potential. Antioxidants (Basel) 2022;11(5):892. doi: 10.3390/antiox11050892.

52. Benatti P, Peluso G, Nicolai R, Calvani M. Polyunsaturated Fatty Acids: Biochemical, Nutritional and Epigenetic Properties. J Am Coll Nutr 2004;23(4):281-302. doi: 10.1080/07315724.2004.10719371.

53. Dupasquier CM, Dibrov E, Kneesh AL, Cheung PK, Lee KG, Alexander HK, et al. Dietary Flaxseed Inhibits Atherosclerosis in the LDL Receptor-Deficient Mouse in Part Through Antiproliferative and Anti-Inflammatory Actions. Am J Physiol Heart Circ Physiol 2007;293(4):H2394-402. doi: 10.1152/ajpheart.01104.2006.

54. Askarpour M, Karimi M, Hadi A, Ghaedi E, Symonds ME, Miraghajani M, et al. Effect of Flaxseed Supplementation on Markers of Inflammation and Endothelial Function: A Systematic Review and Meta-Analysis. Cytokine 2020;126:154922. doi: 10.1016/j.cyto.2019.154922.

55. Rahimlou M, Jahromi NB, Hasanyani N, Ahmadi AR. Effects of Flaxseed Interventions on Circulating Inflammatory Biomarkers: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Adv Nutr 2019;10(6):1108-119. doi: 10.1093/advances/nmz048.

56. Jelinek GA, Hadgkiss EJ, Weiland TJ, Pereira NG, Marck CH, van der Meer DM. Association of Fish Consumption and Ω 3 Supplementation with Quality of life, Disability and Disease Activity in an International Cohort of People with Multiple Sclerosis. Int J Neurosci 2013;123(11):792-800. doi: 10.3109/00207454.2013.803104.

57. Parks NE, Jackson-Tarlton CS, Vacchi L, Merdad R, Johnston BC. Dietary Interventions for Multiple Sclerosis-Related Outcomes. Cochrane Database Syst Rev 2020;5(5):CD004192. doi: 10.1002/14651858.CD004192.pub4.

58. Kuo CH, Chou YC, Liao KC, Shieh CJ, Deng TS. Optimization of Light Intensity, Temperature, and Nutrients to Enhance the Bioactive Content of Hyperforin and Rutin in St. John's Wort. Molecules 2020;25(18):4256. doi: 10.3390/molecules25184256.

59. Murch SJ, Saxena PK. St. John’s wort (Hypericum perforatum L.): Challenges and Strategies for Production of Chemically-Consistent Plants. Can J Plant Sci 2006;86(3): 765-71. Doi:10.4141/P05-179

60. Nosratabadi R, Rastin M, Sankian M, Haghmorad D, Mahmoudi M. Hyperforin-Loaded Gold Nanoparticle Alleviates Experimental Autoimmune Encephalomyelitis by suppressing Th1 and Th17 Cells and Upregulating Regulatory T Cells. Nanomedicine 2016;12(7):1961-71. doi: 10.1016/j.nano.2016.04.001.

61. Selek S, Esrefoglu M, Meral I, Bulut H, Caglar HG, Sonuc G, et al. Effects of Oenothera Biennis L. and Hypericum Perforatum L. Extracts on Some Central Nervous System Myelin Proteins, Brain Histopathology and Oxidative Stress in Mice with Experimental Autoimmune Encephalomyelitis. Biotech Histochem 2019;94(2):75-83. doi: 10.1080/10520295.2018.1482001.

62. Hou M, Wang R, Zhao S, Wang Z. Ginsenosides in Panax Genus and Their Biosynthesis. Acta Pharm Sin B 2021;11(7):1813-34. doi: 10.1016/j.apsb.2020.12.017

63. Ratan ZA, Haidere MF, Hong YH, Park SH, Lee JO, Lee J, et al. Pharmacological Potential of Ginseng and its Major Component Ginsenosides. J Ginseng Res 2021;45(2):199-210. doi: 10.1016/j.jgr.2020.02.004.

64. Lu J, Wang X, Wu A, Cao Y, Dai X, Liang Y, Li X. Ginsenosides in Central Nervous System Diseases: Pharmacological Actions, Mechanisms, and Therapeutics. Phytother Res 2022;36(4):1523-1544. doi: 10.1002/ptr.7395.

65. Lee MJ, Chang BJ, Oh S, Nah SY, Cho IH. Korean Red Ginseng Mitigates Spinal Demyelination in a Model of Acute Multiple Sclerosis by Downregulating p38 Mitogen-Activated Protein Kinase and Nuclear Factor-κB Signaling Pathways. J Ginseng Res 2018;42(4):436-46. doi: 10.1016/j.jgr.2017.04.013.

66. Lee MJ, Choi JH, Kwon TW, Jo HS, Ha Y, Nah SY, Cho IH. Korean Red Ginseng Extract Ameliorates Demyelination by Inhibiting Infiltration and Activation of Immune Cells in Cuprizone-Administrated Mice. J Ginseng Res 2023;47(5):672-680. doi: 10.1016/j.jgr.2023.05.001.

67. Oh J, Kwon TW, Choi JH, Kim Y, Moon SK, Nah SY, Cho IH. Ginsenoside-Re Inhibits Experimental Autoimmune Encephalomyelitis as a Mouse Model of Multiple Sclerosis by Downregulating TLR4/MyD88/NF-κB Signaling Pathways. Phytomedicine 2024;122:155065. doi: 10.1016/j.phymed.2023.155065.

68. Kim E, Cameron M, Lovera J, Schaben L, Bourdette D, Whitham R. American Ginseng does not Improve Fatigue in Multiple Sclerosis: A Single Center Randomized Double-Blind Placebo-Controlled Crossover Pilot Study. Mult Scler 2011;17(12):1523-6. doi: 10.1177/1352458511412062

69. Etemadifar M, Sayahi F, Abtahi SH, Shemshaki H, Dorooshi GA, Goodarzi M, et al. Ginseng in the Treatment of Fatigue in Multiple Sclerosis: A Randomized, Placebo-Controlled, Double-Blind Pilot Study. Int J Neurosci 2013;123(7):480-6. doi: 10.3109/00207454.2013.764499.

70. Benameur T, Giacomucci G, Panaro MA, Ruggiero M, Trotta T, Monda V, et al. New Promising Therapeutic Avenues of Curcumin in Brain Diseases. Molecules 2021;27(1):236. doi: 10.3390/molecules27010236.

71. Mohajeri M, Sadeghizadeh M, Najafi F, Javan M. Polymerized Nano-Curcumin Attenuates Neurological Symptoms in EAE Model of Multiple Sclerosis Through Down Regulation of Inflammatory and Oxidative Processes and Enhancing Neuroprotection and Myelin Repair. Neuropharmacology 2015;99:156-67. doi:10.1016/j.neuropharm.2015.07.013

72. Xie L, Li XK, Funeshima-Fuji N, Kimura H, Matsumoto Y, Isaka Y, et al. Amelioration of Experimental Autoimmune Encephalomyelitis by Curcumin Treatment Through Inhibition of IL17 Production. Int Immunopharmacol 2009;9(5):575-81. doi: 10.1016/j.intimp.2009.01.025.

73. Sadek MA, Rabie MA, El Sayed NS, Sayed HM, Kandil EA. Neuroprotective Effect of Curcumin Against Experimental Autoimmune Encephalomyelitis-Induced Cognitive and Physical Impairments in Mice: An Insight into the Role of the AMPK/SIRT1 Pathway. Inflammopharmacology 2023. doi: 10.1007/s10787-023-01399-3.

74. Mavaddatiyan L, Khezri S, Abtahi Froushani SM. Molecular Effects of Curcumin on the Experimental Autoimmune Encephalomyelitis. Vet Res Forum 2021 Winter;12(1):47-52. doi: 10.30466/vrf.2019.98789.2356.

75. 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. doi: 10.18502/ijaai.v22i6.14646.

76. Dolati S, Ahmadi M, Rikhtegar R, Babaloo Z, Ayromlou H, Aghebati-Maleki L, et al. Changes in Th17 Cells Function After Nanocurcumin Use to Treat Multiple Sclerosis. Int Immunopharmacol 2018;61:74-81. doi: 10.1016/j.intimp.2018.05.018.

77. Dolati S, Babaloo Z, Ayromlou H, Ahmadi M, Rikhtegar R, Rostamzadeh D, et al. Nanocurcumin Improves Regulatory T-Cell Frequency and Function in Patients with Multiple Sclerosis. J Neuroimmunol 2019;327:15-21. doi: 10.1016/j.jneuroim.2019.01.007.

78. Petracca M, Quarantelli M, Moccia M, Vacca G, Satelliti B, D'Ambrosio G, Carotenuto A, Ragucci M, Assogna F, Capacchione A, Lanzillo R, Morra VB. Prospective Study to Evaluate Efficacy, Safety and Tolerability of Dietary Supplement of Curcumin (BCM95) in Subjects with Active Relapsing Multiple Sclerosis Treated with Subcutaneous Interferon Beta 1a 44 mcg tiw (CONTAIN): A Randomized, Controlled Trial. Mult Scler Relat Disord 2021;56:103274. doi: 10.1016/j.msard.2021.103274.

79. Jones E, Vlachou S. A Critical Review of the Role of the Cannabinoid Compounds ∆9-Tetrahydrocannabinol (∆9-THC) and Cannabidiol (CBD) and Their Combination in Multiple Sclerosis Treatment. Molecules 2020;25:4930. doi:10.3390/molecules25214930.

80. Slaven M, Levine O. Cannabinoids for Symptoms of Multiple Sclerosis: Benefits to Patients Still Unclear. JAMA Netw Open 2018;1(6):e183484. doi: 10.1001/jamanetworkopen.2018.3484.

81. Oláh A, Szekanecz Z, Bíró T. Targeting Cannabinoid Signaling in the Immune System: “High”-ly Exciting Questions, Possibilities, and Challenges. Front Immunol 2017;8:1487. Doi:10.3389/fimmu.2017.01487.

82. Torres-Moreno MC, Papaseit E, Torrens M, Farré M. Assessment of Efficacy and Tolerability of Medicinal Cannabinoids in Patients with Multiple Sclerosis: A Systematic Review and Meta-Analysis. JAMA Netw Open 2018;1(6):e183485. doi: 10.1001/jamanetworkopen.2018.3485.