Immunogenic Potential of Natural Products

  • Rahul L. Gajbhiye
  • Sanjit K. Mahato
  • Anushree Achari
  • Parasuraman Jaisankar
  • V. Ravichandiran


The immune system is the most complex and important biological system of the human body, and good health requires it to be strong and well-functioning. Imbalance or malfunction of the immune system leads to a wide range of chronic diseases, including allergies, cancers, autoimmune diseases, and others. Immunogenicity mainly refers to any changes in the immune response and may involve amplification, induction, expression or inhibition of different components of the immune response. Immunomodulators can be broadly classified into three categories: immunoadjuvants, immunostimulants, and immunosuppressants. Natural products-based immunogenic agents provide a safe alternative for treatment in order to avoid the unwanted side effects of synthetic drugs. A wide range of structurally diverse plant secondary metabolites, such as alkaloids, polysaccharides, lectins, glycosides, phenolic compounds, flavonoids, anthocyanins, tannins, saponins, terpenoids, and sterols can improve and/or activate macrophage immune responses, leading to immunomodulation, antitumor activity, wound-healing, and other therapeutic effects.


Immunomodulators Natural products Plant secondary metabolites Cytokine Innate and adaptive immunity T regulatory cell Th1 Th2 


  1. Abbas AK, Murphy KM, Sher A (1996) Functional diversity of helper T lymphocytes. Nature 383(6603):787–793. CrossRefPubMedGoogle Scholar
  2. Aderem A, Ulevitch RJ (2000) Toll-like receptors in the induction of the innate immune response. Nature 406(6797):782–787. CrossRefPubMedGoogle Scholar
  3. Aguayo C, Casado J, Gonzalez M, Pearson JD, Martin RS, Casanello P, Pastor-Anglada M, Sobrevia L (2005) Equilibrative nucleoside transporter 2 is expressed in human umbilical vein endothelium, but is not involved in the inhibition of adenosine transport induced by hyperglycaemia. Placenta 26(8–9):641–653. CrossRefPubMedGoogle Scholar
  4. Ahmad A, Sharif-Askari E, Fawaz L, Menezes J (2000) Innate immune response of the human host to exposure with herpes simplex virus type 1: in vitro control of the virus infection by enhanced natural killer activity via interleukin-15 induction. J Virol 74(16):7196–7203CrossRefGoogle Scholar
  5. Amirghofran Z, Hashemzadeh R, Javidnia K, Golmoghaddam H, Esmaeilbeig A (2011) In vitro immunomodulatory effects of extracts from three plants of the Labiatae family and isolation of the active compound(s). J Immunotoxicol 8(4):265–273. CrossRefPubMedGoogle Scholar
  6. Aranha I, Clement F, Venkatesh YP (2012) Immunostimulatory properties of the major protein from the stem of the Ayurvedic medicinal herb, guduchi (Tinospora cordifolia). J Ethnopharmacol 139(2):366–372. CrossRefPubMedGoogle Scholar
  7. Bao XL, Yuan HH, Wang CZ, Fan W, Lan MB (2015) Polysaccharides from Cymbopogon citratus with antitumor and immunomodulatory activity. Pharm Biol 53(1):117–124. CrossRefPubMedGoogle Scholar
  8. Bordbar N, Karimi MH, Amirghofran Z (2012) The effect of glycyrrhizin on maturation and T cell stimulating activity of dendritic cells. Cell Immunol 280(1):44–49. CrossRefPubMedGoogle Scholar
  9. Brownson DM, Azios NG, Fuqua BK, Dharmawardhane SF, Mabry TJ (2002) Flavonoid effects relevant to cancer. J Nutr 132(11 Suppl):3482S–3489S. CrossRefPubMedGoogle Scholar
  10. Burana-Osot J, Pattanapanyasat K, Soonthornchareonnon N, Sukapirom K, Toida T (2010) Characterisation and immuno-stimulating activity of polysaccharides from Thai medicinal plants. Nat Prod Res 24(15):1403–1412. CrossRefPubMedGoogle Scholar
  11. Burnet M (1959) Auto-immune disease. II. Pathology of the immune response. Br Med J 2(5154):720–725CrossRefGoogle Scholar
  12. Chang SL, Chiang YM, Chang CL, Yeh HH, Shyur LF, Kuo YH, Wu TK, Yang WC (2007) Flavonoids, centaurein and centaureidin, from Bidens pilosa, stimulate IFN-gamma expression. J Ethnopharmacol 112(2):232–236. CrossRefPubMedGoogle Scholar
  13. Correa MG, Pires PR, Ribeiro FV, Pimentel SZ, Casarin RC, Cirano FR, Tenenbaum HT, Casati MZ (2017) Systemic treatment with resveratrol and/or curcumin reduces the progression of experimental periodontitis in rats. J Periodontal Res 52(2):201–209. CrossRefPubMedGoogle Scholar
  14. Cox JC, Coulter AR (1997) Adjuvants – a classification and review of their modes of action. Vaccine 15(3):248–256CrossRefGoogle Scholar
  15. Das A, Jawed JJ, Das MC, Sandhu P, De UC, Dinda B, Akhter Y, Bhattacharjee S (2017) Antileishmanial and immunomodulatory activities of lupeol, a triterpene compound isolated from Sterculia villosa. Int J Antimicrob Agents 50(4):512–522. CrossRefPubMedGoogle Scholar
  16. Davidson A, Diamond B (2001) Autoimmune diseases. N Engl J Med 345(5):340–350. CrossRefGoogle Scholar
  17. Dong GC, Chuang PH, Forrest MD, Lin YC, Chen HM (2006) Immuno-suppressive effect of blocking the CD28 signaling pathway in T-cells by an active component of Echinacea found by a novel pharmaceutical screening method. J Med Chem 49(6):1845–1854. CrossRefPubMedGoogle Scholar
  18. Erukainure OL, Mesaik MA, Atolani O, Muhammad A, Chukwuma CI, Islam MS (2017) Pectolinarigenin from the leaves of Clerodendrum volubile shows potent immunomodulatory activity by inhibiting T – cell proliferation and modulating respiratory oxidative burst in phagocytes. Biomed Pharmacother 93:529–535. CrossRefPubMedGoogle Scholar
  19. Feldman KS, Sahasrabudhe K, Smith RS, Scheuchenzuber WJ (1999) Immunostimulation by plant polyphenols: a relationship between tumor necrosis factor-alpha production and tannin structure. Bioorg Med Chem Lett 9(7):985–990CrossRefGoogle Scholar
  20. Feng X, Wang Y, Hao Y, Ma Q, Dai J, Liang Z, Liu Y, Li X, Song Y, Si C (2017) Vinpocetine inhibited the CpG oligodeoxynucleotide-induced immune response in plasmacytoid dendritic cells. Immunol Invest 46(3):263–273. CrossRefPubMedGoogle Scholar
  21. Ferreira SS, Passos CP, Madureira P, Vilanova M, Coimbra MA (2015) Structure-function relationships of immunostimulatory polysaccharides: a review. Carbohydr Polym 132:378–396. CrossRefPubMedGoogle Scholar
  22. Figueroa JE, Densen P (1991) Infectious diseases associated with complement deficiencies. Clin Microbiol Rev 4(3):359–395CrossRefGoogle Scholar
  23. Gamal-Eldeen AM, Ahmed EF, Abo-Zeid MA (2009) In vitro cancer chemopreventive properties of polysaccharide extract from the brown alga, Sargassum latifolium. Food Chem Toxicol 47(6):1378–1384. CrossRefPubMedGoogle Scholar
  24. Gao F, Yao YC, Cai SB, Zhao TR, Yang XY, Fan J, Li XN, Cao JX, Cheng GG (2017) Novel immunosuppressive pregnane glycosides from the leaves of Epigynum auritum. Fitoterapia 118:107–111. CrossRefPubMedGoogle Scholar
  25. Geissmann F, Manz MG, Jung S, Sieweke MH, Merad M, Ley K (2010) Development of monocytes, macrophages, and dendritic cells. Science 327(5966):656–661. CrossRefPubMedPubMedCentralGoogle Scholar
  26. Giavasis I (2014) Bioactive fungal polysaccharides as potential functional ingredients in food and nutraceuticals. Curr Opin Biotechnol 26:162–173. CrossRefPubMedGoogle Scholar
  27. Gross G, Waks T, Eshhar Z (1989) Expression of immunoglobulin-T-cell receptor chimeric molecules as functional receptors with antibody-type specificity. Proc Natl Acad Sci U S A 86(24):10024–10028CrossRefGoogle Scholar
  28. Grundemann C, Thell K, Lengen K, Garcia-Kaufer M, Huang YH, Huber R, Craik DJ, Schabbauer G, Gruber CW (2013) Cyclotides suppress human T-lymphocyte proliferation by an interleukin 2-dependent mechanism. PLoS One 8(6):e68016. CrossRefPubMedPubMedCentralGoogle Scholar
  29. Guha KP, Mukherjee B, Mukherjee R (1979) Bisbenzylisoquinoline alkaloids – a review. J Nat Prod 42(1):1–84. CrossRefPubMedGoogle Scholar
  30. Gupta PK, Chakraborty P, Kumar S, Singh PK, Rajan MG, Sainis KB, Kulkarni S (2016) G1-4A, a Polysaccharide from Tinospora cordifolia inhibits the survival of Mycobacterium tuberculosis by modulating host immune responses in TLR4 dependent manner. PLoS One 11(5):e0154725. CrossRefPubMedPubMedCentralGoogle Scholar
  31. Hadden JW (1993) Immunostimulants. Immunol Today 14(6):275–280. CrossRefPubMedGoogle Scholar
  32. Haque MA, Jantan I, Arshad L, Bukhari SNA (2017) Exploring the immunomodulatory and anticancer properties of zerumbone. Food Funct 8(10):3410–3431. CrossRefPubMedGoogle Scholar
  33. Hertog MG, Kromhout D, Aravanis C, Blackburn H, Buzina R, Fidanza F, Giampaoli S, Jansen A, Menotti A, Nedeljkovic S et al (1995) Flavonoid intake and long-term risk of coronary heart disease and cancer in the seven countries study. Arch Intern Med 155(4):381–386CrossRefGoogle Scholar
  34. Ho LJ, Juan TY, Chao P, Wu WL, Chang DM, Chang SY, Lai JH (2004) Plant alkaloid tetrandrine downregulates IkappaBalpha kinases-IkappaBalpha-NF-kappaB signaling pathway in human peripheral blood T cell. Br J Pharmacol 143(7):919–927. CrossRefPubMedPubMedCentralGoogle Scholar
  35. Hsieh YS, Chien C, Liao SK, Liao SF, Hung WT, Yang WB, Lin CC, Cheng TJ, Chang CC, Fang JM, Wong CH (2008) Structure and bioactivity of the polysaccharides in medicinal plant Dendrobium huoshanense. Bioorg Med Chem 16(11):6054–6068. CrossRefPubMedGoogle Scholar
  36. Huh JE, Koh PS, Seo BK, Park YC, Baek YH, Lee JD, Park DS (2014) Mangiferin reduces the inhibition of chondrogenic differentiation by IL-1beta in mesenchymal stem cells from subchondral bone and targets multiple aspects of the Smad and SOX9 pathways. Int J Mol Sci 15(9):16025–16042. CrossRefPubMedPubMedCentralGoogle Scholar
  37. Im SA, Kim K, Lee CK (2006) Immunomodulatory activity of polysaccharides isolated from Salicornia herbacea. Int Immunopharmacol 6(9):1451–1458. CrossRefPubMedGoogle Scholar
  38. Islamuddin M, Chouhan G, Want MY, Ozbak HA, Hemeg HA, Afrin F (2016) Immunotherapeutic potential of eugenol emulsion in experimental visceral leishmaniasis. PLoS Negl Trop Dis 10(10):e0005011. CrossRefPubMedPubMedCentralGoogle Scholar
  39. Iwasaki A, Medzhitov R (2004) Toll-like receptor control of the adaptive immune responses. Nat Immunol 5(10):987–995. CrossRefPubMedGoogle Scholar
  40. Jan TR, Farraj AK, Harkema JR, Kaminski NE (2003) Attenuation of the ovalbumin-induced allergic airway response by cannabinoid treatment in A/J mice. Toxicol Appl Pharmacol 188(1):24–35CrossRefGoogle Scholar
  41. Jenny M, Schrocksnadel S, Uberall F, Fuchs D (2010) The potential role of cannabinoids in modulating serotonergic signaling by their influence on tryptophan metabolism. Pharmaceuticals (Basel) 3(8):2647–2660. CrossRefGoogle Scholar
  42. Jia Y, Jing J, Bai Y, Li Z, Liu L, Luo J, Liu M, Chen H (2011) Amelioration of experimental autoimmune encephalomyelitis by plumbagin through down-regulation of JAK-STAT and NF-kappaB signaling pathways. PLoS One 6(10):e27006. CrossRefPubMedPubMedCentralGoogle Scholar
  43. Jiao G, Yu G, Zhang J, Ewart HS (2011) Chemical structures and bioactivities of sulfated polysaccharides from marine algae. Mar Drugs 9(2):196–223. CrossRefPubMedPubMedCentralGoogle Scholar
  44. Kamboh AA, Hang SQ, Khan MA, Zhu WY (2016) In vivo immunomodulatory effects of plant flavonoids in lipopolysaccharide-challenged broilers. Animal 10(10):1619–1625. CrossRefPubMedGoogle Scholar
  45. Kasimu R, Chen C, Xie X, Li X (2017) Water-soluble polysaccharide from Erythronium sibiricum bulb: structural characterisation and immunomodulating activity. Int J Biol Macromol 105(Pt 1):452–462. CrossRefPubMedGoogle Scholar
  46. Kawaguchi K, Alves Sde M, Watanabe T, Kikuchi S, Satake M, Kumazawa Y (1998) Colony stimulating factor-inducing activity of isoflavone C-glucosides from the bark of Dalbergia monetaria. Planta Med 64(7):653–655. CrossRefPubMedGoogle Scholar
  47. Kayser O, Masihi KN, Kiderlen AF (2003) Natural products and synthetic compounds as immunomodulators. Expert Rev Anti-Infect Ther 1(2):319–335CrossRefGoogle Scholar
  48. Kilani-Jaziri S, Mustapha N, Mokdad-Bzeouich I, El Gueder D, Ghedira K, Ghedira-Chekir L (2016) Flavones induce immunomodulatory and anti-inflammatory effects by activating cellular anti-oxidant activity: a structure-activity relationship study. Tumour Biol 37(5):6571–6579. CrossRefPubMedGoogle Scholar
  49. Kinoshita K, Morikawa K, Fujita M, Natori S (1992) Inhibitory effects of plant secondary metabolites on cytotoxic activity of polymorphonuclear leucocytes. Planta Med 58(2):137–145. CrossRefPubMedGoogle Scholar
  50. Koko WS, Mesaik MA, Ranjitt R, Galal M, Choudhary MI (2015) Immunosuppressive phenolic compounds from Hydnora abyssinica A. Braun. BMC Complement Altern Med 15:400. CrossRefPubMedPubMedCentralGoogle Scholar
  51. Kondo Y, Imai Y, Hojo H, Hashimoto Y, Nozoe S (1992) Selective inhibition of T-cell-dependent immune responses by bisbenzylisoquinoline alkaloids in vivo. Int J Immunopharmacol 14(7):1181–1186CrossRefGoogle Scholar
  52. Krauss S, Buttgereit F, Brand MD (1999) Effects of the mitogen concanavalin A on pathways of thymocyte energy metabolism. Biochim Biophys Acta 1412(2):129–138CrossRefGoogle Scholar
  53. Lai Y, Xue Y, Zhang M, Zhang J, Tang W, Liu J, Lei L, Yan J, Luo Z, Zuo J, Li Y, Yao G, Zhang Y (2013) Scapiformolactones A-I: germacrane sesquiterpenoids with an unusual Delta3-15,6-lactone moiety from Salvia scapiformis. Phytochemistry 96:378–388. CrossRefPubMedGoogle Scholar
  54. Lembo S, Balato A, Di Caprio R, Cirillo T, Giannini V, Gasparri F, Monfrecola G (2014) The modulatory effect of ellagic acid and rosmarinic acid on ultraviolet-B-induced cytokine/chemokine gene expression in skin keratinocyte (HaCaT) cells. Biomed Res Int 2014:346793. CrossRefPubMedPubMedCentralGoogle Scholar
  55. Lerouxel O, Cavalier DM, Liepman AH, Keegstra K (2006) Biosynthesis of plant cell wall polysaccharides – a complex process. Curr Opin Plant Biol 9(6):621–630. CrossRefPubMedGoogle Scholar
  56. Li S, Bian F, Yue L, Jin H, Hong Z, Shu G (2014) Selenium-dependent antitumor immunomodulating activity of polysaccharides from roots of A. membranaceus. Int J Biol Macromol 69:64–72. CrossRefPubMedGoogle Scholar
  57. Li Q, Niu Y, Xing P, Wang C (2018) Bioactive polysaccharides from natural resources including Chinese medicinal herbs on tissue repair. Chin Med 13:7. CrossRefPubMedPubMedCentralGoogle Scholar
  58. Lima TF, Rocha JD, Guimaraes-Costa AB, Barbosa-Filho JM, Decote-Ricardo D, Saraiva EM, Arruda LB, Piuvezam MR, Pecanha LM (2014) Warifteine, an alkaloid purified from Cissampelos sympodialis, inhibits neutrophil migration in vitro and in vivo. J Immunol Res 2014:752923. CrossRefPubMedPubMedCentralGoogle Scholar
  59. Liu Q, Shu X, Sun A, Sun Q, Zhang C, An H, Liu J, Cao X (2008a) Plant-derived small molecule albaconol suppresses LPS-triggered proinflammatory cytokine production and antigen presentation of dendritic cells by impairing NF-kappaB activation. Int Immunopharmacol 8(8):1103–1111. CrossRefPubMedGoogle Scholar
  60. Liu Q, Shu X, Wang L, Sun A, Liu J, Cao X (2008b) Albaconol, a plant-derived small molecule, inhibits macrophage function by suppressing NF-kappaB activation and enhancing SOCS1 expression. Cell Mol Immunol 5(4):271–278. CrossRefPubMedPubMedCentralGoogle Scholar
  61. Liu Z, Yuan X, Luo Y, He Y, Jiang Y, Chen ZK, Sun E (2009) Evaluating the effects of immunosuppressants on human immunity using cytokine profiles of whole blood. Cytokine 45(2):141–147. CrossRefPubMedGoogle Scholar
  62. Liu X, Zhang X, Ye L, Yuan H (2016) Protective mechanisms of berberine against experimental autoimmune myocarditis in a rat model. Biomed Pharmacother 79:222–230. CrossRefPubMedGoogle Scholar
  63. Malone JC, Cohen S, Liu SR, Vaillant GE, Waldinger RJ (2013) Adaptive midlife defense mechanisms and late-life health. Pers Individ Differ 55(2):85–89. CrossRefGoogle Scholar
  64. Marshall JD, Kearns GL (1999) Developmental pharmacodynamics of cyclosporine. Clin Pharmacol Ther 66(1):66–75. CrossRefPubMedGoogle Scholar
  65. Martin S, Cantin E, Rouse BT (1988) Cytotoxic T lymphocytes. Their relevance in herpesvirus infections. Ann N Y Acad Sci 532:257–272CrossRefGoogle Scholar
  66. Medzhitov R, Janeway CA Jr (1997) Innate immunity: impact on the adaptive immune response. Curr Opin Immunol 9(1):4–9CrossRefGoogle Scholar
  67. Metzger JA (2014) Adaptive defense mechanisms: function and transcendence. J Clin Psychol 70(5):478–488. CrossRefPubMedGoogle Scholar
  68. Mustapha N, Mokdad-Bzeouich I, Sassi A, Abed B, Ghedira K, Hennebelle T, Chekir-Ghedira L (2016) Immunomodulatory potencies of isolated compounds from Crataegus azarolus through their antioxidant activities. Tumour Biol 37(6):7967–7980. CrossRefPubMedGoogle Scholar
  69. Nair PK, Rodriguez S, Ramachandran R, Alamo A, Melnick SJ, Escalon E, Garcia PI Jr, Wnuk SF, Ramachandran C (2004) Immune stimulating properties of a novel polysaccharide from the medicinal plant Tinospora cordifolia. Int Immunopharmacol 4(13):1645–1659. CrossRefPubMedGoogle Scholar
  70. Nasr-Bouzaiene N, Sassi A, Bedoui A, Krifa M, Chekir-Ghedira L, Ghedira K (2016) Immunomodulatory and cellular antioxidant activities of pure compounds from Teucrium ramosissimum Desf. Tumour Biol 37(6):7703–7712. CrossRefPubMedGoogle Scholar
  71. Nazeam JA, Gad HA, Esmat A, El-Hefnawy HM, Singab AB (2017) Aloe arborescens polysaccharides: in vitro immunomodulation and potential cytotoxic activity. J Med Food 20(5):491–501. CrossRefPubMedGoogle Scholar
  72. Ogechukwu OE, Ogoamaka OP, Sylvester NC, Kawamura A, Proksch P (2011) Immunomodulatory activity of a lupane triterpenoid ester isolated from the eastern Nigeria mistletoe, Loranthus micranthus (Linn). Asian Pac J Trop Med 4(7):514–522. CrossRefPubMedGoogle Scholar
  73. Olafsdottir ES, Ingolfsdottir K (2001) Polysaccharides from lichens: structural characteristics and biological activity. Planta Med 67(3):199–208. CrossRefPubMedGoogle Scholar
  74. Owellen RJ, Owens AH Jr, Donigian DW (1972) The binding of vincristine, vinblastine and colchicine to tubulin. Biochem Biophys Res Commun 47(4):685–691CrossRefGoogle Scholar
  75. Pandey R, Maurya R, Singh G, Sathiamoorthy B, Naik S (2005) Immunosuppressive properties of flavonoids isolated from Boerhaavia diffusa Linn. Int Immunopharmacol 5(3):541–553. CrossRefPubMedGoogle Scholar
  76. Pardo Andreu GL, Maurmann N, Reolon GK, de Farias CB, Schwartsmann G, Delgado R, Roesler R (2010) Mangiferin, a naturally occurring glucoxilxanthone improves long-term object recognition memory in rats. Eur J Pharmacol 635(1–3):124–128. CrossRefPubMedGoogle Scholar
  77. Park CM, Song YS (2013) Luteolin and luteolin-7-O-glucoside inhibit lipopolysaccharide-induced inflammatory responses through modulation of NF-kappaB/AP-1/PI3K-Akt signaling cascades in RAW 264.7 cells. Nutr Res Pract 7(6):423–429. CrossRefPubMedPubMedCentralGoogle Scholar
  78. Prasad R, Singh T, Katiyar SK (2017) Honokiol inhibits ultraviolet radiation-induced immunosuppression through inhibition of ultraviolet-induced inflammation and DNA hypermethylation in mouse skin. Sci Rep 7(1):1657. CrossRefPubMedPubMedCentralGoogle Scholar
  79. Prescott TA, Veitch NC, Simmonds MS (2011) Direct inhibition of calcineurin by caffeoyl phenylethanoid glycosides from Teucrium chamaedrys and Nepeta cataria. J Ethnopharmacol 137(3):1306–1310. CrossRefPubMedGoogle Scholar
  80. Proksch P, Giaisi M, Treiber MK, Palfi K, Merling A, Spring H, Krammer PH, Li-Weber M (2005) Rocaglamide derivatives are immunosuppressive phytochemicals that target NF-AT activity in T cells. J Immunol 174(11):7075–7084CrossRefGoogle Scholar
  81. Ramos S (2007) Effects of dietary flavonoids on apoptotic pathways related to cancer chemoprevention. J Nutr Biochem 18(7):427–442. CrossRefGoogle Scholar
  82. Ramstead AG, Schepetkin IA, Quinn MT, Jutila MA (2012) Oenothein B, a cyclic dimeric ellagitannin isolated from Epilobium angustifolium, enhances IFNgamma production by lymphocytes. PLoS One 7(11):e50546. CrossRefPubMedPubMedCentralGoogle Scholar
  83. Ravikanth V, Niranjan Reddy VL, Ramesh P, Prabhakar Rao T, Diwan PV, Khar A, Venkateswarlu Y (2001) An immunosuppressive tryptophan-derived alkaloid from Lepidagathis cristata. Phytochemistry 58(8):1263–1266CrossRefGoogle Scholar
  84. Seow WK, Ferrante A, Goh DB, Chalmers AH, Li SY, Thong YH (1988) In vitro immunosuppressive properties of the plant alkaloid tetrandrine. Int Arch Allergy Appl Immunol 85(4):410–415CrossRefGoogle Scholar
  85. Shrestha G, St Clair LL, O’Neill KL (2015) The immunostimulating role of lichen polysaccharides: a review. Phytother Res 29(3):317–322. CrossRefPubMedGoogle Scholar
  86. Siegel S (1976) Morphine analgesic tolerance: its situation specificity supports a Pavlovian conditioning model. Science 193(4250):323–325CrossRefGoogle Scholar
  87. Singh UP, Singh NP, Singh B, Hofseth LJ, Taub DD, Price RL, Nagarkatti M, Nagarkatti PS (2012) Role of resveratrol-induced CD11b(+) Gr-1(+) myeloid derived suppressor cells (MDSCs) in the reduction of CXCR3(+) T cells and amelioration of chronic colitis in IL-10(−/−) mice. Brain Behav Immun 26(1):72–82. CrossRefPubMedGoogle Scholar
  88. Singh DK, Gulati K, Ray A (2016) Effects of chelidonic acid, a secondary plant metabolite, on mast cell degranulation and adaptive immunity in rats. Int Immunopharmacol 40:229–234. CrossRefPubMedGoogle Scholar
  89. Siveen KS, Kuttan G (2012) Modulation of humoral immune responses and inhibition of proinflammatory cytokines and nitric oxide production by 10-methoxycanthin-6-one. Immunopharmacol Immunotoxicol 34(1):116–125. CrossRefPubMedGoogle Scholar
  90. Srinivas TR, Meier-Kriesche HU, Kaplan B (2005) Pharmacokinetic principles of immunosuppressive drugs. Am J Transplant 5(2):207–217. CrossRefPubMedGoogle Scholar
  91. Su PF, Staniforth V, Li CJ, Wang CY, Chiao MT, Wang SY, Shyur LF, Yang NS (2008) Immunomodulatory effects of phytocompounds characterized by in vivo transgenic human GM-CSF promoter activity in skin tissues. J Biomed Sci 15(6):813–822. CrossRefPubMedGoogle Scholar
  92. Thell K, Hellinger R, Schabbauer G, Gruber CW (2014) Immunosuppressive peptides and their therapeutic applications. Drug Discov Today 19(5):645–653. CrossRefPubMedPubMedCentralGoogle Scholar
  93. Tzianabos AO (2000) Polysaccharide immunomodulators as therapeutic agents: structural aspects and biologic function. Clin Microbiol Rev 13(4):523–533CrossRefGoogle Scholar
  94. Vasil’eva IS, Paseshnichenko VA (1996) Steroid glycosides from suspension cultures of Dioscorea deltoidea cells and their biological activity. Adv Exp Med Biol 404:15–22CrossRefGoogle Scholar
  95. Vivier E, Tomasello E, Baratin M, Walzer T, Ugolini S (2008) Functions of natural killer cells. Nat Immunol 9(5):503–510. CrossRefPubMedGoogle Scholar
  96. Wang L, Li C, Lin Q, Zhang X, Pan H, Xu L, Shi Z, Ouyang D, He X (2015) Cucurbitacin E suppresses cytokine expression in human Jurkat T cells through down-regulating the NF-kappaB signaling. Acta Biochim Biophys Sin (Shanghai) 47(6):459–465. CrossRefGoogle Scholar
  97. Weidmann J, Craik DJ (2016) Discovery, structure, function, and applications of cyclotides: circular proteins from plants. J Exp Bot 67(16):4801–4812. CrossRefPubMedGoogle Scholar
  98. Wink M (2003) Evolution of secondary metabolites from an ecological and molecular phylogenetic perspective. Phytochemistry 64(1):3–19CrossRefGoogle Scholar
  99. Wong CK, Leung KN, Fung KP, Choy YM (1994) Immunomodulatory and anti-tumour polysaccharides from medicinal plants. J Int Med Res 22(6):299–312. CrossRefPubMedGoogle Scholar
  100. Xing X, Cui SW, Nie S, Phillips GO, Goff HD, Wang Q (2015) Study on Dendrobium officinale O-acetyl-glucomannan (Dendronan(R)): part II. Fine structures of O-acetylated residues. Carbohydr Polym 117:422–433. CrossRefPubMedGoogle Scholar
  101. Xiong H, Tian L, Zhao Z, Chen S, Zhao Q, Hong J, Xie Y, Zhou N, Fu Y (2017) The sinomenine enteric-coated microspheres suppressed the TLR/NF-kappaB signaling in DSS-induced experimental colitis. Int Immunopharmacol 50:251–262. CrossRefPubMedGoogle Scholar
  102. Yamamoto R, Yamamoto Y, Imai S, Fukutomi R, Ozawa Y, Abe M, Matuo Y, Saito K (2014) Effects of various phytochemicals on indoleamine 2,3-dioxygenase 1 activity: galanal is a novel, competitive inhibitor of the enzyme. PLoS One 9(2):e88789. CrossRefPubMedPubMedCentralGoogle Scholar
  103. Yamassaki FT, Lenzi RM, Campestrini LH, Bovo F, Seyfried M, Soldera-Silva A, Stevan-Hancke FR, Zawadzki-Baggio SF, Pettolino FA, Bacic A, Maurer JB (2015) Effect of the native polysaccharide of cashew-nut tree gum exudate on murine peritoneal macrophage modulatory activities. Carbohydr Polym 125:241–248. CrossRefPubMedGoogle Scholar
  104. Zhang AH, Wang XQ, Han WB, Sun Y, Guo Y, Wu Q, Ge HM, Song YC, Ng SW, Xu Q, Tan RX (2013) Discovery of a new class of immunosuppressants from Trichothecium roseum co-inspired by cross-kingdom similarity in innate immunity and pharmacophore motif. Chem Asian J 8(12):3101–3107. CrossRefPubMedGoogle Scholar
  105. Zhang L, Zhang D, Jia Q, Wang R, Dorje G, Zhao Z, Guo F, Yang Y, Li Y (2015) 19(4 – >3)-abeo-abietane diterpenoids from Scrophularia dentata Royle ex Benth. Fitoterapia 106:72–77. CrossRefPubMedGoogle Scholar
  106. Zheng W, Zhao T, Feng W, Wang W, Zou Y, Zheng D, Takase M, Li Q, Wu H, Yang L, Wu X (2014) Purification, characterization and immunomodulating activity of a polysaccharide from flowers of Abelmoschus esculentus. Carbohydr Polym 106:335–342. CrossRefPubMedGoogle Scholar
  107. Zhong JJ (2001) Biochemical engineering of the production of plant-specific secondary metabolites by cell suspension cultures. Adv Biochem Eng Biotechnol 72:1–26PubMedGoogle Scholar
  108. Zhong Z, Connor HD, Li X, Mason RP, Forman DT, Lemasters JJ, Thurman RG (2006) Reduction of ciclosporin and tacrolimus nephrotoxicity by plant polyphenols. J Pharm Pharmacol 58(11):1533–1543. CrossRefPubMedGoogle Scholar
  109. Ziaei A, Amirghofran Z, Zapp J, Ramezani M (2011) Immunoinhibitory effect of teuclatriol a guaiane sesquiterpene from Salvia mirzayanii. Iran J Immunol 8(4):226–235. doi:IJIv8i4A5PubMedGoogle Scholar

Copyright information

© Springer Nature Singapore Pte Ltd. 2019

Authors and Affiliations

  • Rahul L. Gajbhiye
    • 1
    • 2
  • Sanjit K. Mahato
    • 3
    • 4
  • Anushree Achari
    • 2
  • Parasuraman Jaisankar
    • 2
  • V. Ravichandiran
    • 1
  1. 1.National Institute of Pharmaceutical Education and Research (NIPER)KolkataIndia
  2. 2.Organic and Medicinal Chemistry DivisionCSIR-Indian Institute of Chemical BiologyKolkataIndia
  3. 3.TCG Lifesciences Private LimitedKolkataIndia
  4. 4.Department of Applied Chemistry, Graduate School of EngineeringOsaka UniversitySuitaJapan

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