Herbal Medicines for Immunosuppression


Herbal medicines have been used for centuries to treat different illnesses. Among more than 20,000 herbal medicines available for humans, a limited number have sufficiently been studied and numerous remained to be investigated for their efficacy in treating human diseases.
A number of herbal products are in use for their immunosuppressive effects. This capacity of herbs may have useful applications in immune-mediated disorders including autoimmune diseases and organ transplant rejection. Plants such as Salvia miltiorrhiza and Tripterygium wilfordii has been shown to reduce inflammatory cytokines and mediators, indicating their value in the treatment of acute graft rejections and autoimmunity. Tanacetum parthenium inhibits the release of pro-inflammatory mediators from macrophages and lymphocytes and Curcuma longa down regulates the expression of cytokines and chemokines as well as the transcription factor NF- kappaB. There has been growing interest to investigate novel anti-inflammatory or immunosuppressive activities from various sources particularly herbal medicines.
This review focuses on the plants that have recently received more attention regarding their influence on the immune system, being reported as immunosuppressive and anti-inflammatory agents and promising protective effects for immune-mediated diseases.

1. Konig R, Zhou W. Signal transduction in T helper cells: CD4 coreceptors exert complex regulatory effects on T cell activation and function. Curr Issues Mol Biol 2004;6(1):1-15.
2. McHeyzer-Williams M, McHeyzer-Williams L, Panus J, Pogue-Caley R, Bikah G, Driver D, et al. Helper T-cell- regulated B-cell immunity. Microbes Infect 2003; 5(3):205-12.
3. Afzali B, Mitchell P, Lechler RI, John S, Lombardi G.Translational Mini-Review Series on Th17 Cells:Induction of interleukin-17 production by regulatory Tcells. Clin Exp Immunol 2010; 159(2):120-30.
4. Bettini M, Vignali DA. Regulatory T cells and inhibitory cytokines in autoimmunity. Curr Opin Immunol 2009;21(6):612-8.
5. Licastro F, Davis LJ, Morini MC. Lectins and superantigens: membrane interactions of these compounds with T lymphocytes affect immune responses. Int J Biochem 1993; 25(6):845-52.
6. Kunz M, Ibrahim SM. Cytokines and cytokine profiles in human autoimmune diseases and animal models of autoimmunity. Mediators Inflamm 2009; 2009: 979258.
7. Perretti M, D'Acquisto F. Annexin A1 and glucocorticoids as effectors of the resolution of inflammation. Nat Rev Immunol 2009; 9(1):62-70.
8. De Bosscher K, Van Craenenbroeck K, Meijer OC, Haegeman G. Selective transrepression versus transactivation mechanisms by glucocorticoid receptor modulators in stress and immune systems. Eur J Pharmacol 2008; 583(2-3):290-302.
9. van der Laan S, Meijer OC. Pharmacology of glucocorticoids: beyond receptors. Eur J Pharmacol 2008; 585(2-3):483-91.
10. Dooley MA, Nair R. Therapy Insight: preserving fertility in cyclophosphamide-treated patients with rheumatic disease. Nat Clin Pract Rheumatol 2008; 4(5):250-7.
11. Brode S, Cooke A. Immune-potentiating effects of the chemotherapeutic drug cyclophosphamide. Crit Rev Immunol 2008; 28(2):109-26.
12. Hulin A. Today in molecular mechanisms of immunosuppressive drugs actions: roles of pharmacist. Ann Pharm Fr 2008; 66(2):102-14.
13. Allison AC. Immunosuppressive drugs: the first 50 years and a glance forward. Immunopharmacol 2000; 47(2-3):63-83.
14. Metalidis C, Kuypers DR. Emerging Immunosuppressive Drugs in Kidney Transplantation. Curr Clin Pharmacol 2011; 6(2):130-6.
15. Gabardi S, Martin ST, Roberts KL, Grafals M. Induction immunosuppressive therapies in renal transplantation. Am J Health Syst Pharm 2011; 68(3):211-8.
16. Hubbard R, Tattersfield A, Smith C, West J, Smeeth L, Fletcher A. Use of inhaled corticosteroids and the risk of fracture. Chest 2006; 130(4):1082-8.
17. Scarpignato C, Hunt RH. Nonsteroidal anti-inflammatory drug-related injury to the gastrointestinal tract: clinical picture, pathogenesis, and prevention. Gastroenterol Clin North Am 2010; 39(3):433-64.
18. Rezzani R. Exploring cyclosporine A-side effects and the protective role-played by antioxidants: the morphological and immunohistochemical studies. Histol Histopathol 2006; 21(3):301-16.
19. Aulakh R, Singh S. Strategies for minimizing corticosteroid toxicity: a review. Indian J Pediatr 2008;75(10):1067-73.
20. Mirshafiey A, Khorramizadeh MR, Saadat F, Rehm BH.Chemopreventive effect of M2000, a new anti- inflammatory agent. Med Sci Monit 2004; 10(10):105-9.
21. Perl A. Pathogenesis and spectrum of autoimmunity.Methods Mol Med 2004; 102:1-8.
22. Ramaswamy M, Deng M, Siegel RM. Harnessing programmed cell death as a therapeutic strategy in rheumatic diseases. Nat Rev Rheumatol 2011; 7(3):152-60.
23. Krasovsky J, Chang DH, Deng G, Yeung S, Lee M, Leung PC, et al. Inhibition of human dendritic cell activation by hydroethanolic but not lipophilic extracts of turmeric (Curcuma longa). Planta Med 2009; 75(4):312-5.
24. 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 IL-17 production. Int Immunopharmacol 2009; 9(5):575-81.
25. Jurenka JS. Anti-inflammatory properties of curcumin, a major constituent of Curcuma longa: a review of preclinical and clinical research. Altern Med Rev 2009;14(2):141-53.
26. Decoté-Ricardo D, Chagas KK, Rocha JD, Redner P, Lopes UG, Cambier JC, et al. Modulation of in vitro murine B-lymphocyte response by curcumin. Phytomedicine 2009; 16(10):982-8.
27. Mathema VB, Koh YS, Thakuri BC, Sillanpää M.Parthenolide, a Sesquiterpene Lactone, Expresses Multiple Anti-cancer and Anti-inflammatory Activities. Inflammation 2012;35(2):560-5
28. Marks WH. Tripterygium wilfordii Hook F. versus Sulfasalazine in the treatmentof rheumatoid arthritis: a well-designed clinical trial of a botanicaldemonstrating effectiveness. Fitoterapia 2011; 82(1):85-7.
29. Xiao C, Zhao L, Liu Z, Lu C, Zhao N, Yang D, et al. The effect of triptolide on CD4+ and CD8+ cells in the Peyer's patch of DA rats with collagen induced arthritis. Nat Prod Res 2009; 23(18):1699-706.
30. Wang Y, Jia L, Wu CY. Triptolide inhibits the differentiation of Th17 cells and suppressesn collagen-induced arthritis. Scand J Immunol 2008;68(4):383-90.
31. Setty AR, Sigal LH. Herbal medications commonly used in the practice of rheumatology: mechanisms of action, efficacy, and side effects. Semin Arthritis Rheum 2005;34(6):773-84.
32. Wilasrusmee C, Siddiqui J, Bruch D, Wilasrusmee S, Kittur S, Kittur DS. In vitro immunomodulatory effects of herbal products. Am Surg 2002; 68(10):860-4.
33. Ni YF, Kuai JK, Lu ZF, Yang GD, Fu HY, Wang J, et al.Glycyrrhizin treatment is associated with attenuation of lipopolysaccharide-induced acute lung injury by inhibiting cyclooxygenase-2 and inducible nitric oxide synthase expression. J Surg Res 2011; 165(1):29-35.
34. Xie YC, Dong XW, Wu XM, Yan XF, Xie QM.Inhibitory effects of flavonoids extracted from licorice on lipopolysaccharide-induced acute pulmonary inflammation in mice. Int Immunopharmacol 2009; 9(2):194-200.
35. Cassano N, Mantegazza R, Battaglini S, Apruzzi D, Loconsole F, Vena GA. Adjuvant role of a new emollient cream in patients with palmar and/or plantar psoriasis: a pilot randomized open-label study. G Ital Dermatol Venereol 2010; 145(6):789-92.
36. Barfod L, Kemp K, Hansen M, Kharazmi A. Chalcones from Chinese liquorice inhibit proliferation of T cells and production of cytokines. Int Immunopharmacol 2002;2(4):545-55.
37. Gumpricht E, Dahl R, Devereaux MW, Sokol RJ.Licorice compounds glycyrrhizin and 18β-glycyrrhetinic acid are potent modulators of bile acid-induced cytotoxicity in rat hepatocytes. J Biol Chem 2005;280(11): 10556–63.
38. Capasso F, Mascolo N, Autore G, Duraccio MR.Glycyrrhetinic acid, leucocytes and prostaglandins. J Pharm Pharmacol 1983; 35(5): 332–5.
39. Li J, Tu Y, Tong L, Zhang W, Zheng J, Wei Q.Immunosuppressive activity on the murine immune responses of glycyrol fromGlycyrrhiza uralensis via inhibition of calcineurin activity. Pharm Biol 2010; 48(10):1177-84.
40. Ho JH, Hong CY. Salvianolic Acids: small compounds with multiple mechanisms for cardiovascular protection. J Biomed Sci 2011; 18(1):30.
41. Wang X, Wang Y, Jiang M, Zhu Y, Hu L, Fan G, et al.Differential cardioprotective effects of salvianolic acid and tanshinone on acute myocardial infarction are mediated by unique signaling pathways. J Ethnopharmacol 2011; 135(3):662-71.
42. Peng GL, Zhang XY. Effects of Salvia miltiorrhiza on serum levels of inflammatory cytokines in patients with severe acute pancreatitis. Zhong Xi Yi Jie He Xue Bao 2007; 5(1):28-31.
43. Wan JM, Sit WH, Lee CL, Fu KH, Chan DK. Protection of lethal toxicity of endotoxin by Salvia miltiorrhiza BUNGE is via reduction in tumor necrosis factor alpha release and liver injury. Int Immunopharmacol 2006;6(5):750-8.
44. Qin XY, Li T, Yan L, Liu QS, Tian Y. Tanshinone IIA protects against immune-mediated liver injury through activation of t-cell subsets and regulation of cytokines. Immunopharmacol Immunotoxicol 2010; 32(1):51-5.
45. Kawaguchi K, Matsumoto T, Kumazawa Y. Effects of Antioxidant Polyphenols on TNF-alpha-Related Diseases. Curr Top Med Chem 2011; 11(14):1767-79.
46. Hsu SD, Dickinson DP, Qin H, Borke J, Ogbureke KU,Winger JN, et al. Green tea polyphenols reduce autoimmune symptoms in a murine model for human Sjogren's syndrome and protect human salivary acinar cells from TNF-alpha- induced cytotoxicity. Autoimmunity 2007; 40(2):138-47.
47. Yoneyama S, Kawai K, Tsuno NH, Okaji Y, Asakage M, Tsuchiya T, et al. Epigallocatechin gallate affects human dendritic cell differentiation and maturation. J Allergy Clin Immunol 2008; 121(1):209-14.
48. Aktas O, Prozorovski T, Smorodchenko A, Savaskan NE, Lauster R, Kloetzel PM, et al. Green tea epigallocatechin-
3-gallate mediates T cellular NF-kappa B inhibition and exerts neuroprotection in autoimmune encephalomyelitis. J Immunol 2004; 173(9):5794-800.
49. Wang Y, Mei Y, Feng D, Xu L. Triptolide modulates T-cell inflammatory responses and ameliorates experimental autoimmune encephalomyelitis. J Neurosci Res 2008; 86(11):2441-9.
50. Wong KF, Chan JK, Chan KL, Tam P, Yang D, Fan ST,et al. Immunochemical characterization of the functional constituents of Tripterygium wilfordii contributing to its anti-inflammatory property. Clin Exp Pharmacol Physiol 2008; 35(1):55-9.
51. Xu W, Lin Z, Yang C, Zhang Y, Wang G, Xu X, et al.Immunosuppressive effects of demethylzeylasteral in a rat kidney transplantation model. Int Immunopharmacol 2009; 9(7-8):996-1001.
52. Luo CN, Lin X, Li WK, Pu F, Wang LW, Xie SS, et al.Effect of berbamine on T-cell mediated immunity and the prevention of rejection on skin transplants in mice. J Ethnopharmacol 1998; 59(3):211-5.
53. Ren Y, Lu L, Guo TB, Qiu J, Yang Y, Liu A, et al. Novel immunomodulatory properties of berbamine through selective down-regulation of STAT4 and action of IFN gamma in experimental autoimmune encephalomyelitis. J Immunol 2008; 181(2):1491-8
54. Colic M, Vucevic D, Kilibarda V, Radicevic N, Savic M.Modulatory effects of garlic extracts on proliferation of T-lymphocytes in vitro stimulated with concanavalin A. Phytomedicine 2002; 9(2):117-24.
55. Hodge G, Hodge S, Han P. Allium sativum (garlic) suppresses leukocyte inflammatory cytokine production in vitro: potential therapeutic use in the treatment of inflammatory bowel disease. Cytometry 2002; 48(4):209-15.
56. Benammar C, Hichami A, Yessoufou A, Simonin AM, Belarbi M, Allali H, et al. Zizyphus lotus L. (Desf.) modulates antioxidant activity and human T-cell proliferation. BMC Complement Altern Med 2010;24;10:54.
57. Hong T, Jin GB, Yoshino G, Miura M, Maeda Y, Cho S, et al. Protective effects of Polygalae root in experimental TNBS-induced colitis in mice. J Ethnopharmacol 2002;79(3):341-6.
58. Amirghofran Z, Bahmani M, Azadmehr A, Javidnia K.Immunomodulatory and apoptotic effects of Stachys obtusicrena on proliferative lymphocytes. Med Sci Monit 2007; 13(6):145-50.
59. Amirghofran Z, Azadmehr A, Javidnia K. Haussknechtia elymatica: a plant with immunomodulatory effects. Iran J Immunol 2007; 4(1):26-31.
60. Amirghofran Z, Javidnia K, Bahmani M, Azadmehr A, Esmaeilbeig M. The effect of the methanol extract of galium mite on the cellular immunity and antibody synthesis. J Immunoassay Immunochem 2011;32(3): 157-169.
61. Amirghofran Z, Bahmani M, Javidnia K, Azadmehr A.Immunomodulatory activities of various medicinal plant extracts: Effects on human lymphocytes apoptosis. Immunol Invest 2009; 38(2): 181-192.
62. Amirghofran Z, Hashemzadeh R, Javidnia K, Golmoghaddam H, Esmaeilbeig A. In vitro immunomodulatory effects of extracts from three plants of the Labiatae family and isolation of the active compound(s). J Immunotoxicol 2011; 8(4):265-73.
63. Gharagozloo M, Velardi E, Bruscoli S, Agostini M, Di Sante M, Donato V, et al. Silymarin suppress CD4+ T cell activation and proliferation: effects on NF-kappaB activity and IL-2 production. Pharmacol Res 2010;61(5):405-9.
64. Shou QY, Fu RZ, Tan Q, Shen ZW. Geranylated flavonoids from the roots of Campylotropis hirtella and their immunosuppressive activities. J Agric Food Chem 2009; 57(15):6712-9.
65. Burgos RA, Hancke JL, Bertoglio JC, Aguirre V, Arriagada S, Calvo M, 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.
66. Chao CY, Lii CK, Tsai IT, Li CC, Liu KL, Tsai CW, et al. Andrographolide Inhibits ICAM-1 Expression and NF-κB Activation in TNF-α-Treated EA.hy926 Cells. J Agric Food Chem 2011; 59(10):5263-71.
67. Akbar S. Andrographis paniculata: a review of pharmacological activities and clinical effects. Altern Med Rev 2011; 16(1):66-77.
68. Sun Y, Cai TT, Zhou XB, Xu Q. Saikosaponin a inhibits the proliferation and activation of T cells through cell cycle arrest and induction of apoptosis. Int Immunopharmacol 2009; 9(7-8):978-83.
69. Leung CY, Liu L, Wong RN, Zeng YY, Li M, Zhou H.Saikosaponin-d inhibits T cell activation through the modulation of PKCtheta, JNK, and NF-kappaB transcription factor. Biochem Biophys Res Commun 2005; 338(4):1920-7.
70. Park MA, Kim HJ. Anti-inflammatory constituents isolated from Clerodendron trichotomum Tunberg Leaves (CTL) inhibits pro-inflammatory gene expression in LPS- stimulated RAW 264.7 macrophages by suppressing NF- kappaB activation. Arch Pharm Res 2007; 30(6):755-60.
71. Lee JY, Lee JG, Sim SS, Whang WK, Kim CJ. Anti asthmatic effects of phenylpropanoid glycosides from Clerodendron trichotomum leaves and Rumex gmelini herbes in conscious guinea-pigs challenged with aerosolized ovalbumin. Phytomedicine 2011; 18(2-3):134-42.
72. Zhang J, Ni J, Chen ZH, Li X, Zhang RJ, Tang W, et al.Periplocoside A prevents experimental autoimmune encephalomyelitis by suppressing IL-17 production and inhibits differentiation of Th17 cells. Acta Pharmacol Sin 2009; 30(8):1144-52.
73. Wan J, Zhu YN, Feng JQ, Chen HJ, Zhang RJ, Ni J, et al.Periplocoside A, a pregnane glycoside from Periploca sepium Bge, prevents concanavalin A-induced mice hepatitis through inhibiting NKT-derived inflammatory cytokine productions. Int Immunopharmacol 2008;8(9):1248-56.
74. Sun Y, Wu XX, Yin Y, Gong FY, Shen Y, Cai TT, et al.Novel immunomodulatory properties of cirsilineol through selective inhibition of IFN-gamma signaling in a murine model of inflammatory bowel disease. Biochem Pharmacol 2010; 79(2):229-38.
75. Wang J, Sun Y, Li Y, Xu Q. Aqueous extract from aerial parts of Artemisia vestita, a traditional Tibetan medicine, reduces contact sensitivity in mice by down-regulating the activation, adhesion and metalloproteinase production of T lymphocytes. Int Immunopharmacol 2005; 5(2):407-15.
76. Amirghofran Z, Bahmani M, Azadmehr A, Javidnia K,Ramazani M, Ziaei A. Effect of Salvia mirzayanii on immune system and induction of apoptosis in peripheral blood lymphocytes. Nat. Prod. Res. 2010; 24(6):500-8.
77. Ziaei A, Ramezani M, Wright L, Paetz C, Schneider B,Amirghofran Z. Identification of spathulenol in Salvia mirzayanii and the immunomodulatory effects. Phytother Res 2011, 25(4); 557-62.
78. Amirghofran Z, Azadbakht M, Karimi MH. Evaluation of the immunomodulatory effects of five herbal plants. J Ethnopharmacol 2000; 72(1-2):167-12.
79. Amirghofran Z. Medicinal plants as immunosuppressive agents in traditional Iranian medicine. Iran J Immunol 2010; 7(2):65-73.
80. Faham N, Javidnia K, Bahmani M, Amirghofran Z.Calycopterin, an immunoinhibitory compound from the extract of Dracocephalum kotschyi. Phytother Res 2008;22(9):1154-58.
81. Chauhan PS, Gupta KK, Bani S. The immunosuppressive effects of Agyrolobium roseum and pinitol in experimental animals. Int Immunopharmacol 2011;11(2):286-91

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Herbal medicines Immunosuppression

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Amirghofran Z. Herbal Medicines for Immunosuppression. Iran J Allergy Asthma Immunol. 1;11(2):111-119.