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Current Immunology Reviews (Discontinued)


ISSN (Print): 1573-3955
ISSN (Online): 1875-631X

Review Article

Immunomodulation in Multiple Sclerosis by Phytotherapy

Author(s): Maryam Bahrami, Ghasem Mosayebi, Ali Ghazavi and Ali Ganji*

Volume 16, Issue 1, 2020

Page: [28 - 36] Pages: 9

DOI: 10.2174/1573395516999200930122850

Price: $65


Multiple sclerosis is a chronic inflammatory and demyelinating disorder of the central nervous system (CNS) that can cause cognition, mobility, and sensory impairments. Studies have shown that the immune system through inflammation and autoreactive T cells are involved in the progression of MS. The present article aimed to review the potent anti-inflammatory, antioxidant, and immunomodulatory agents that could modulate the immune response in MS. In herbal medicine, various medicinal plants including Olive, Silybum marianum, Grape, Pomegranate peel extract, Nigella sativa, Turmeric, Green tea, Aloysia citrodora, Boswellia papyrifera, Boswellia serrata, Ruta graveolens, and Andrographis paniculata are known with therapeutic benefits in MS patients through immunoregulation and reduction of major symptoms.

Keywords: Multiple sclerosis, immunomodulatory plants, herbal medicine, alternative medicine, inflammation, neurodegenerative disease.

Graphical Abstract
Compston A, Coles A. Multiple sclerosis. Lancet 2002; 359(9313): 1221-31.
[] [PMID: 11955556]
Jobin C, Larochelle C, Parpal H, Coyle PK, Duquette P. Gender issues in multiple sclerosis: an update. Womens Health (Lond) 2010; 6(6): 797-820.
[] [PMID: 21118039]
Efendi H, Karabudak R, Kantarci O, Siva A. Understanding multiple sclerosis better in 2014-Environmental factors, remyelination, diagnostic techniques, treatment decisions and the future focus of multiple sclerosis treatment. Eur Neurol Rev 2015; 10(2): 148-56.
Grigoriadis N, van Pesch V. ParadigMS Group. A basic overview of multiple sclerosis immunopathology. Eur J Neurol 2015; 22(S2)(Suppl. 2): 3-13.
[] [PMID: 26374508]
Murray TJ. Diagnosis and treatment of multiple sclerosis. BMJ 2006; 332(7540): 525-7.
[] [PMID: 16513709]
Dargahi N, Katsara M, Tselios T, et al. Multiple Sclerosis: Immunopathology and Treatment Update. Brain Sci 2017; 7(7): E78.
[] [PMID: 28686222]
Mainardi T, Kapoor S, Bielory L. Complementary and alternative medicine: herbs, phytochemicals and vitamins and their immunologic effects. J Allergy Clin Immunol 2009; 123(2): 283-94.
[] [PMID: 19203652]
Yadav V, Bever C Jr, Bowen J, et al. 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.
[] [PMID: 24663230]
Santangelo C, Vari R, Scazzocchio B, et al. Anti-inflammatory activity of extra virgin olive oil polyphenols: which role in the prevention and treatment of immune-mediated inflammatory diseases? Endocr Metab Immune Disord Drug Targets 2018; 18(1): 36-50.
[PMID: 29141574]
Conde C, Escribano BM, Luque E, et al. The protective effect of extra-virgin olive oil in the experimental model of multiple sclerosis in the rat. Nutr Neurosci 2018; 1-12.
[PMID: 29730972]
Miljkovic D, Dekanski D, Miljkovic Z, Momcilovic M, Mostarica-Stojkovic M. Dry olive leaf extract ameliorates experimental autoimmune encephalomyelitis Clinical nutrition (Edinburgh, Scotland) 2009; 28(3): 346-50.
Esmaeil N, Anaraki SB, Gharagozloo M, Moayedi B. Silymarin impacts on immune system as an immunomodulator: One key for many locks. Int Immunopharmacol 2017; 50: 194-201.
[] [PMID: 28672215]
Min K, Yoon W-K, Kim SK. Immunosuppressive effect of silibinin in experimental autoimmune encephalomyelitis 2007; 30(10): 1265-72.
Navabi F, Shaygannejad V, Abbasirad F, et al. Immunoregulatory Effects of Silymarin on Proliferation and Activation of Th1 Cells Isolated from Newly Diagnosed and IFN-ss1b-Treated MS Patients. Inflammation 2018.
[PMID: 30178232]
Imler TJ Jr, Petro TM. Decreased severity of experimental autoimmune encephalomyelitis during resveratrol administration is associated with increased IL-17+IL-10+ T cells, CD4(-) IFN-gamma+ cells, and decreased macrophage IL-6 expression. Int Immunopharmacol 2009; 9(1): 134-43.
[] [PMID: 19022403]
Petro TM. Regulatory role of resveratrol on Th17 in autoimmune disease. Int Immunopharmacol 2011; 11(3): 310-8.
[] [PMID: 20708723]
Shindler KS, Ventura E, Dutt M, Elliott P, Fitzgerald DC, Rostami A. Oral resveratrol reduces neuronal damage in a model of multiple sclerosis Journal of neuro-ophthalmology : the official journal of the North American Neuro-Ophthalmology Society 2010; 30(4): 328-9.
Fonseca-Kelly Z, Nassrallah M, Uribe J, et al. Resveratrol neuroprotection in a chronic mouse model of multiple sclerosis. Front Neurol 2012; 3: 84.
[] [PMID: 22654783]
Pervin M, Unno K, Ohishi T, Tanabe H, Miyoshi N, Nakamura Y. Beneficial Effects of Green Tea Catechins on Neurodegenerative Diseases. Molecules 2018; 23(6): E1297.
[] [PMID: 29843466]
Yang F, Oz HS, Barve S, de Villiers WJ, McClain CJ, Varilek GW. The green tea polyphenol (-) epigallocatechin-3-gallate blocks nuclear factor-κ B activation by inhibiting I κ B kinase activity in the intestinal epithelial cell line IEC-6. Mol Pharmacol 2001; 60(3): 528-33.
[PMID: 11502884]
Felgines C, Fraisse D, Besson C, Vasson M-P, Texier O. Bioavailability of lemon verbena (Aloysia triphylla) polyphenols in rats: impact of colonic inflammation. Br J Nutr 2014; 111(10): 1773-81.
[] [PMID: 24513110]
Mauriz E, Vallejo D, Tuñón MJ, Rodriguez-López JM, et al. Effects of dietary supplementation with lemon verbena extracts on serum inflammatory markers of multiple sclerosis patients Randomized Controlled Trial 2015; 31(2): 764-1.
Patti F. Standardised Frankincense extract: new possible therapeutic option for patients with relapsing-remitting multiple sclerosis. J Neurol Neurosurg Psychiatry 2018; 89(4): 327.
[] [PMID: 29275327]
Sedighi B, Pardakhty A, Kamali H, Shafiee K. Effect of Boswellia papyrifera on cognitive impairment in multiple sclerosis Iran J Neurol 2014; 13(3): 149.
Stuerner K, Stellmann J, Paul F, Doerr J, Martin R, Heesen C, Eds. Safety, tolerability and efficacy of Boswellic acids in relapsing-remitting multiple sclerosis-the SABA proof-of-concept trial.Multiple sclerosis journal. Sage publications ltd 1 olivers yard, 55 city road, London ec1y 1sp, England 2014.
Loonat F, Amabeoku GJ. Antinociceptive, anti-inflammatory and antipyretic activities of the leaf methanol extract of Ruta graveolens L. (Rutaceae) in mice and rats. Afr J Tradit Complement Altern Med 2014; 11(3): 173-81.
[] [PMID: 25371580]
Bohuslavizki K, Hänsel W, Kneip A, Koppenhöfer E. Reimers AJGp. Potassium channel blockers from Ruta-a new approach for the treatment of multiple sclerosis Gen Physiol Biophy 1992; 11: 507.
Iruretagoyena MI, Tobar JA, González PA, et al. Andrographolide interferes with T cell activation and reduces experimental autoimmune encephalomyelitis in the mouse. J Pharmacol Exp Ther 2005; 312(1): 366-72.
[] [PMID: 15331658]
Carretta MD, Alarcón P, Jara E, et al. Andrographolide reduces IL-2 production in T-cells by interfering with NFAT and MAPK activation. Eur J Pharmacol 2009; 602(2-3): 413-21.
[] [PMID: 19038244]
Bertoglio J, Baumgartner M, Palma R, Ciampi E, Carcamo C, Cáceres D, et al. Andrographis paniculata decreases fatigue in patients with relapsing-remitting multiple sclerosis: a 12-month double-blind placebo-controlled pilot study 2016; 16(1): 77.
Mohamed A, Waris HM, Ramadan H, Quereshi M, Kalra J. Amelioration of chronic relapsing experimental autoimmune encephalomyelitis (cr-eae) using thymoquinone - biomed. Biomed Sci Instrum 2009; 45: 274-9.
[PMID: 19369775]
Mohamed A, Shoker A, Bendjelloul F, et al. Improvement of experimental allergic encephalomyelitis (EAE) by thymoquinone; an oxidative stress inhibitor. Biomed Sci Instrum 2003; 39: 440-5.
[PMID: 12724933]
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.
[PMID: 15850137]
Spate S, Ramadan H H, Mohamed A. Interleukins (IL-7 and IL-7r) gene expression and thymoquinones role in the amelioration of eae symptoms - biomed 2010. Biomed Sci Instrum 2010; 46: 190-85.
[PMID: 20467093]
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.
[PMID: 26261504]
Fahey AJ, Adrian Robins R, Constantinescu CS. Curcumin modulation of IFN-beta and IL-12 signalling and cytokine induction in human T cells. J Cell Mol Med 2007; 11(5): 1129-37.
[] [PMID: 17979888]
Natarajan C. Curcumin inhibits experimental allergic encephalomyelitis by blocking IL-12 signaling through Janus kinase-STAT pathway in T lymphocytes 2002; 168(12): 6506-13.
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.
[] [PMID: 22402368]
Lian YT, Yang XF, Wang ZH, et al. Curcumin serves as a human kv1.3 blocker to inhibit effector memory T lymphocyte activities. Phytother Res 2013; 27(9): 1321-7.
[] [PMID: 23132777]
Ghanaatian N, Lashgari NA, Abdolghaffari AH, et al. Curcumin as a therapeutic candidate for multiple sclerosis: Molecular mechanisms and targets. J Cell Physiol 2019; 234(8): 12237-48.
[] [PMID: 30536381]
Qureshi M, Al-Suhaimi EA, Wahid F, Shehzad O, Shehzad A. Therapeutic potential of curcumin for multiple sclerosis Neurological Sci 2018; 39(2): 207-14.
Ghaffari S, Hatami H. Dehghan GJRips.. Saffron ethanolic extract attenuates oxidative stress, spatial learning, and memory impairments induced by local injection of ethidium bromide Res Pharm Sci 2015; 10(3): 222.
Ghazavi A, Mosayebi G, Salehi H. Abtahi HJPjobs. Effect of ethanol extract of saffron (Crocus sativus L.) on the inhibition of experimental autoimmune encephalomyelitis in C57bl/6 mice 2009; 12(9): 690.
Alavi MS, Fanoudi S, Fard AV, et al. Safranal Attenuates Excitotoxin-Induced Oxidative OLN-93 Cells Injury. Drug Res (Stuttg) 2019; 69(6): 323-9.
[] [PMID: 30463091]
Zhu A, Lao C, Wang Z, Chen Y, Bai C. Characterization of Crocetin-Monoglucuronide as a Neuron-Protective Metabolite of Crocin-1. Mol Nutr Food Res 2019; e1900024.
[] [PMID: 31034723]
Mosayebi G, Ghazavi A, Salehi H, Payani MA, Khazae MR. Effect of sesame oil on the inhibition of experimental autoimmune encephalomyelitis in C57BL/6 mice. Pak J Biol Sci 2007; 10(11): 1790-6.
[] [PMID: 19086539]
Ghazavi A, Mosayebi G. The mechanism of sesame oil in ameliorating experimental autoimmune encephalomyelitis in C57BL/6 mice. Phytother Res 2012; 26(1): 34-8.
[] [PMID: 21538630]
Faraji F, Hashemi M, Ghiasabadi A, et al. Combination therapy with interferon beta-1a and sesame oil in multiple sclerosis. Complement Ther Med 2019; 45: 275-9.
[] [PMID: 31331574]
Singh V, Sherpa M. Neuronal-like differentiation of murine mesenchymal stem cell line: stimulation by juglans regia L. Oil. Appl Biochem Biotechnol 2017; 183(1): 385-95.
[] [PMID: 28289857]
Ganji A, Farahani I, Palizvan MR, et al. Therapeutic effects of walnut oil on the animal model of multiple sclerosis. Nutr Neurosci 2019; 22(3): 215-22.
[] [PMID: 28891414]
Upton R, Graff A, Jolliffe G, Länger R, Williamson E. American herbal pharmacopoeia: botanical pharmacognosy-microscopic characterization of botanical medicines. CRC Press 2016.
Angeloni C, Malaguti M, Barbalace MC, Hrelia S. Bioactivity of Olive Oil Phenols in Neuroprotection. Int J Mol Sci 2017; 18(11): E2230.
[] [PMID: 29068387]
Torres-Sánchez ED, Pacheco-Moisés FP, Macias-Islas MA, et al. Effect of fish and olive oil on mitochondrial ATPase activity and membrane fluidity in patients with relapsing-remitting multiple sclerosis treated with interferon beta 1-b. Nutr Hosp 2018; 35(1): 162-8.
[PMID: 29565165]
Di Costanzo A, Angelico R. Formulation Strategies for Enhancing the Bioavailability of Silymarin: The State of the Art. Molecules 2019; 24(11): E2155.
[] [PMID: 31181687]
Camont L, Cottart CH, Rhayem Y, et al. Simple spectrophotometric assessment of the trans-/cis-resveratrol ratio in aqueous solutions. Anal Chim Acta 2009; 634(1): 121-8.
[] [PMID: 19154820]
Malaguarnera LJN. Influence of resveratrol on the immune response Journal Nutrients 2019; 11(5): 946.
Mähler A, Steiniger J, Bock M, et al. Metabolic response to epigallocatechin-3-gallate in relapsing-remitting multiple sclerosis: a randomized clinical trial. Am J Clin Nutr 2015; 101(3): 487-95.
[] [PMID: 25733633]
Moussaieff A, Mechoulam R. Boswellia resin: from religious ceremonies to medical uses; a review of in-vitro, in-vivo and clinical trials. J Pharm Pharmacol 2009; 61(10): 1281-93.
[] [PMID: 19814859]
Jiang X, Ma J, Wei Q, Feng X, Qiao L, Liu L, et al. Effect of frankincense extract on nerve recovery in the rat sciatic nerve damage model Evidence-based complementary and alternative medicine eCAM 2016.
Aggarwal BB, Prasad S, Reuter S, et al. Identification of novel anti-inflammatory agents from Ayurvedic medicine for prevention of chronic diseases: “reverse pharmacology” and “bedside to bench” approach. Curr Drug Targets 2011; 12(11): 1595-653.
[] [PMID: 21561421]
San Miguel E. Rue (Ruta L., Rutaceae) in traditional Spain: Frequency and distribution of its medicinal and symbolic applicationsLa Ruda (Ruta L., Rutaceae) en la españa tradicional: Frecuencia y distribución de sus aplicaciones medicinales y simbólicas. Econ Bot 2003; 57(2): 231-44.
Burgos RA, Hancke JL, Bertoglio JC, et al. Efficacy of an Andrographis paniculata composition for the relief of rheumatoid arthritis symptoms: a prospective randomized placebo-controlled trial. Clin Rheumatol 2009; 28(8): 931-46.
[] [PMID: 19408036]
Chevallier A. The encyclopedia of medicinal plants. A practical reference guide to over 550 key herbs & their medicinal uses. Dorling Kindersley London 1996.
Woo CC, Kumar AP, Sethi G, Tan KHB. Thymoquinone: potential cure for inflammatory disorders and cancer. Biochem Pharmacol 2012; 83(4): 443-51.
[] [PMID: 22005518]
Chattopadhyay I, Biswas K, Bandyopadhyay U, Banerjee RK. Turmeric and curcumin: Biological actions and medicinal applications. Curr Sci Bangalore 2004; 87: 44-53.
Schmidt M, Betti G, Hensel A. Saffron in phytotherapy: pharmacology and clinical uses. Wien Med Wochenschr 2007; 157(13-14): 315-9.
[] [PMID: 17704979]
Basker D, Negbi M. Uses of saffron. Econ Bot 1983; 37(2): 228-36.
Ren B, Yuan T, Diao Z, Zhang C, Liu Z, Liu X. Protective effects of sesamol on systemic oxidative stress-induced cognitive impairments via regulation of Nrf2/Keap1 pathway. Food Funct 2018; 9(11): 5912-24.
[] [PMID: 30375618]
Hsu E, Parthasarathy SJC. Anti-inflammatory and antioxidant effects of sesame oil on atherosclerosis: a descriptive literature review Cureus 2017; 9(7): e1438.
Fisher DR, Poulose SM, Bielinski DF, Shukitt-Hale B. Serum metabolites from walnut-fed aged rats attenuate stress-induced neurotoxicity in BV-2 microglial cells. Nutr Neurosci 2017; 20(2): 103-9.
[] [PMID: 25153536]
MacLean CH, Mojica WA, Morton SC, et al. Effects of omega-3 fatty acids on lipids and glycemic control in type II diabetes and the metabolic syndrome and on inflammatory bowel disease, rheumatoid arthritis, renal disease, systemic lupus erythematosus, and osteoporosis: summary AHRQ Evidence Report Summaries. US: Agency for Healthcare Research and Quality 2004.
Wang LM, Yi Y, Yao YL, et al. Walnut oil improves spatial memory in rats and increases the expression of acid-sensing ion channel genes Asic2a and Asic4. Food Sci Nutr 2018; 7(1): 293-301.
[] [PMID: 30680184]

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