Immunomodulatory Potential of Phytochemicals: Recent Updates

  • Nidhi Sharma
  • Herschel S. Dhekne
  • Sabyasachi Senapati


Phytochemicals perform wide array of functions related to plant physiology. Beside these they are often being used as therapeutics for prevention or cure of wide range of human diseases. Phytochemicals considered being exciting metabolites since ages as they play significant role in maintain good health through balanced nutrition and immune homeostasis. Various phytochemicals obtained from different parts of plant comprises of tremendous anti-oxidant, anti-inflammatory, anti-cancerous, neuro- protective and cardio protective properties. Beside these they are often being used as therapeutics for prevention or cure of wide range of human diseases. Easy and specific delivery as well as the bioavailability of phytochemicals considered to be important factors to get benefits of phytochemicals. Recent in vitro and in vivo studies have uncovered the molecular functions of several phytochemicals. Their role in modulating humoral as well as cell mediated immune system has been explored.


Anti-cancerous Anti-inflammatory Bioavailability Immune homeostasis Phytochemicals 


  1. Aldini R, Micucci M, Cevenini M, et al. Anti-inflammatory effect of phytosterols in experimental murine colitis model: prevention, induction, remission study. PLoS One. 2014;9(9):e108112.PubMedPubMedCentralGoogle Scholar
  2. Aqil F, Munagala R, Jeyabalan J, et al. Bioavailability of phytochemicals and its enhancement by drug delivery systems. Cancer Lett. 2013;334(1):133–41.PubMedPubMedCentralGoogle Scholar
  3. Banerjee S, Bueso-Ramos C, Aggarwal BB. Suppression of 7,12-dimethylbenz(a)anthracene-induced mammary carcinogenesis in rats by resveratrol: role of nuclear factor-κB, cyclooxygenase 2, and matrix metalloprotease. Cancer Res. 2002;62:4945–54.PubMedGoogle Scholar
  4. Banerjee S, Ji C, Mayfield JE, Goel A, et al. Ancient drug curcumin impedes 26S proteasome activity by direct inhibition of dual-specificity tyrosine-regulated kinase 2. Proc Natl Acad Sci U S A. 2018;115(32):8155–60.PubMedPubMedCentralGoogle Scholar
  5. Barbieri R, Coppo E, Marchese A, et al. Phytochemicals for human disease: an update on plant-derived compounds antibacterial activity. Microbiol Res. 2017;196:44–68.PubMedGoogle Scholar
  6. Batra P, Sharma AK. Anti-cancer potential of flavonoids: recent trends and future perspectives. Biotech. 2013;3(6):439–59.Google Scholar
  7. Bernabeu E, Cagel M, Lagomarsino E, et al. Paclitaxel: what has been done and the challenges remain ahead. Int J Pharm. 2017;526(1–2):474–95.PubMedGoogle Scholar
  8. Bhattacharya A, Sood P, Citovsky V. The roles of plant phenolics in defence and communication during Agrobacterium and Rhizobium infection. Mol Plant Pathol. 2010;11(5):705–19.PubMedPubMedCentralGoogle Scholar
  9. Chahar MK, Sharma N, Dobhal MP. Flavonoids: a versatile source of anticancer drugs. Pharmacogn Rev. 2011;5(9):1.PubMedPubMedCentralGoogle Scholar
  10. Chang YC, Lee TS, Chiang AN. Quercetin enhances ABCA1 expression and cholesterol efflux through a p38-dependent pathway in macrophages. J Lipid Res. 2012;53(9):1840–50.PubMedPubMedCentralGoogle Scholar
  11. Chang SK, Alasalvar C, Shahidi F. Review of dried fruits: phytochemicals, antioxidant efficacies, and health benefits. J Funct Foods. 2016;21:113–32.Google Scholar
  12. Cherry JD, Olschowka JA, O’Banion MK. Arginase 1+ microglia reduce Aβ plaque deposition during IL-1β-dependent neuroinflammation. J Neuroinflammation. 2015;12:203.PubMedPubMedCentralGoogle Scholar
  13. Chirumbolo S. Plant phytochemicals as new potential drugs for immune disorders and cancer therapy: really a promising path? J Sci Food Agric. 2012;92(8):1573–7.PubMedGoogle Scholar
  14. Chuan LI, Jia Z, Yu-Jiao ZU, et al. Biocompatible and biodegradable nanoparticles for enhancement of anti-cancer activities of phytochemicals. Chin J Nat Med. 2015;13(9):641.PubMedCentralGoogle Scholar
  15. Dancey J, Eisenhauer EA. Current perspectives on camptothecins in cancer treatment. Br J Cancer. 1996;74:327–38.PubMedPubMedCentralGoogle Scholar
  16. Davies DR, Mamat B, Magnusson OT, et al. Discovery of leukotriene A4 hydrolase inhibitors using metabolomics biased fragment crystallography. J Med Chem. 2009;52(15):4694–715.PubMedPubMedCentralGoogle Scholar
  17. Devappa RK, Rakshit SK, Dekker RF. Forest biorefinery: potential of poplar phytochemicals as value-added co-products. Biotechnol Adv. 2015;33(6):681–716.PubMedGoogle Scholar
  18. Egert S, Rimbach G. Which sources of flavonoids: complex diets or dietary supplements? Adv Nutr. 2011;2(1):8–14.PubMedPubMedCentralGoogle Scholar
  19. Emanuela M, Giuseppe C, Sonia C, et al. Vinca alkaloids and analogues as anti-cancer agents: looking back, peering ahead. Bioorg Med Chem Lett. 2018;28:2816–26.Google Scholar
  20. Epriliati I, Ginjom IR. Bioavailability of phytochemicals. In: Phytochemicals – a global perspective of their role in nutrition and health. Rijeka: InTech; 2012.Google Scholar
  21. Fechtner S, Singh A, Chourasia M. Molecular insights into the differences in anti-inflammatory activities of green tea catechins on IL-1β signaling in rheumatoid arthritis synovial fibroblasts. Toxicol Appl Pharmacol. 2017;329:112–20.PubMedPubMedCentralGoogle Scholar
  22. George VC, Dellaire G, Rupasinghe HV. Plant flavonoids in cancer chemoprevention: role in genome stability. J Nutr Biochem. 2017;45:1–14.PubMedGoogle Scholar
  23. Goldyne ME, Burrish GF, Poubelle P. Arachidonic acid metabolism among human mononuclear leukocytes. Lipoxygenase-related pathways. J Biol Chem. 1984;259(14):8815–9.PubMedGoogle Scholar
  24. González-Reyes RE, Nava-Mesa MO, Vargas-Sánchez K. Involvement of astrocytes in Alzheimer’s disease from a neuroinflammatory and oxidative stress perspective. Front Mol Neurosci. 2017;10:427.PubMedPubMedCentralGoogle Scholar
  25. Haeggström JZ. Leukotriene biosynthetic enzymes as therapeutic targets. J Clin Invest. 2018;128(7):2680–90.PubMedPubMedCentralGoogle Scholar
  26. Hevener KE, Verstak TA, Lutat KE. Recent developments in topoisomerase targeted cancer chemotherapy. Acta Pharmaceutica Sinica B. 2018;8(6):844–61.PubMedPubMedCentralGoogle Scholar
  27. Hoensch HP, Weigmann B. Regulation of the intestinal immune system by flavonoids and its utility in chronic inflammatory bowel disease. World J Gastroenterol. 2018;24(8):877–81.PubMedPubMedCentralGoogle Scholar
  28. Holst B, Williamson G. Nutrients and phytochemicals: from bioavailability to bioefficacy beyond antioxidants. Curr Opin Biotechnol. 2008;19(2):73–82.PubMedGoogle Scholar
  29. Huang M, Lu JJ, Huang MQ. Terpenoids: natural products for cancer therapy. Expert Opin Investig Drugs. 2012;21(12):1801–18.PubMedGoogle Scholar
  30. Iqbal J, Abbasi BA, Mahmood T. Plant-derived anticancer agents: a green anticancer approach. Asian Pac J Trop Biomed. 2017;7:1129–50.Google Scholar
  31. Isah T. Anticancer alkaloids from trees: development into drugs. Pharmacogn Rev. 2016;10(20):90.PubMedPubMedCentralGoogle Scholar
  32. Jana NR, Dikshit P, Goswami A, et al. Inhibition of proteasomal function by curcumin induces apoptosis through mitochondrial pathway. J Biol Chem. 2004;279(12):11680–5.PubMedGoogle Scholar
  33. Kim HP, Son KH, Chang HW, et al. Anti-inflammatory plant flavonoids and cellular action mechanisms. J Pharmacol Sci. 2004;96(3):229–45.PubMedGoogle Scholar
  34. Kim YS, Jeong HY, Kim AR, et al. Natural product derivative BIO promotes recovery after myocardial infarction via unique modulation of the cardiac microenvironment. Sci Rep. 2016;6:30726.PubMedPubMedCentralGoogle Scholar
  35. Kiyama R. Estrogenic terpenes and terpenoids: pathways, functions and applications. Eur J Pharmacol. 2017;815:405–15.PubMedGoogle Scholar
  36. Kuo PL, Hsu YL, Chang CH, et al. The mechanism of ellipticine-induced apoptosis and cell cycle arrest in human breast MCF-7 cancer cells. Cancer Lett. 2005;223(2):293–301.PubMedGoogle Scholar
  37. Langhorst J, Varnhagen I, Schneider SB, et al. Randomised clinical trial: a herbal preparation of myrrh, chamomile and coffee charcoal compared with mesalazine in maintaining remission in ulcerative colitis – a double-blind, double-dummy study. Aliment Pharmacol Ther. 2013;38:490–500.PubMedGoogle Scholar
  38. Larussa T, Imeneo M, Luzza F. Potential role of nutraceutical compounds in inflammatory bowel disease. World J Gastroenterol. 2017;23(14):2483–92.PubMedPubMedCentralGoogle Scholar
  39. Las Heras B, Rodriguez B, Bosca L, Villar AM. Terpenoids: sources, structure elucidation and therapeutic potential in inflammation. Curr Top Med Chem. 2003;3(2):171–85.Google Scholar
  40. Le Marchand L. Cancer preventive effects of flavonoids – a review. Biomed Pharmacother. 2002;56(6):296–301.PubMedGoogle Scholar
  41. Leitzmann C. Characteristics and health benefits of phytochemicals. Complement Med Res. 2016;23(2):69–74.Google Scholar
  42. Lin ZY, Kuo CH, Wu DC, et al. Anticancer effects of clinically acceptable colchicine concentrations on human gastric cancer cell lines. Kaohsiung J Med Sci. 2016;32(2):68–73.PubMedGoogle Scholar
  43. Liu RH. Health benefits of fruit and vegetables are from additive and synergistic combinations of phytochemicals. Am J Clin Nutr. 2003;78(3):517S–20S.PubMedGoogle Scholar
  44. López-Lázaro M, Calderón-Montaño JM, Burgos-Morón E. Green tea constituents (-)-epigallocatechin-3-gallate (EGCG) and gallic acid induce topoisomerase I- and topoisomerase II-DNA complexes in cells mediated by pyrogallol-induced hydrogen peroxide. Mutagenesis. 2011;26(4):489–98.PubMedGoogle Scholar
  45. Lou JR, Zhang XX, Zheng J, et al. Transient metals enhance cytotoxicity of curcumin: potential involvement of the NF-kappaB and mTOR signaling pathways. Anticancer Res. 2010;30(9):3249–55.PubMedGoogle Scholar
  46. Man SM. Inflammasomes in the gastrointestinal tract: infection, cancer and gut microbiota homeostasis. Nat Rev Gastroenterol Hepatol. 2018;15(12):721–37. Scholar
  47. Martino E, Della Volpe S, Terribile E, et al. The long story of camptothecin: from traditional medicine to drugs. Bioorg Med Chem Lett. 2017;27(4):701–7.PubMedGoogle Scholar
  48. Matsuura HN, Fett-Neto AG. Plant alkaloids: main features, toxicity, and mechanisms of action. In: Plant toxins. Dordrecht: Springer; 2017. p. 243–61.Google Scholar
  49. McCubrey JA, Lertpiriyapong K, Steelman LS, et al. Effects of resveratrol, curcumin, berberine and other nutraceuticals on aging, cancer development, cancer stem cells and microRNAs. Aging (Albany NY). 2017;9(6):1477.Google Scholar
  50. Molyneux RJ, Lee ST, Gardner DR, et al. Phytochemicals: the good, the bad and the ugly? Phytochemistry. 2007;68(22–24):2973–85.PubMedGoogle Scholar
  51. Moudi M, Go R, Yien CYS, et al. Vinca alkaloids. Int J Prev Med. 2013;4(11):1231.PubMedPubMedCentralGoogle Scholar
  52. Mozaffarian D, Wu JHY. Flavonoids, dairy foods, and cardiovascular and metabolic health: a review of emerging biologic pathways. Circ Res. 2018;122(2):369–84.PubMedPubMedCentralGoogle Scholar
  53. Nabholtz JM, Gligorov J. The role of taxanes in the treatment of breast cancer. Expert Opin Pharmacother. 2005;6(7):1073–94.PubMedGoogle Scholar
  54. Nirmala MJ, Samundeeswari A, Sankar PD. Natural plant resources in anti-cancer therapy-a review. Res Plant Biol. 2011;1(3):1–14.Google Scholar
  55. Oka Y, Iwai S, Amano H, et al. Tea polyphenols inhibit rat osteoclast formation and differentiation. J Pharmacol Sci. 2012;118(1):55–64.PubMedGoogle Scholar
  56. Pan Y, Zhang F, Zhao Y. Berberine enhances chemosensitivity and induces apoptosis through dose-orchestrated AMPK signaling in breast cancer. J Cancer. 2017;8(9):1679.PubMedPubMedCentralGoogle Scholar
  57. Patlolla JMR, Rao CV. Triterpenoids for cancer prevention and treatment: current status and future prospects. Curr Pharm Biotechnol. 2012;13(1):147–55.PubMedGoogle Scholar
  58. Pizzolato JF, Saltz LB. The camptothecins. Lancet. 2003;361(9376):2235–42.PubMedGoogle Scholar
  59. Raza SS, Khan MM, Ahmad A, et al. Neuroprotective effect of naringenin is mediated through suppression of NF-κB signaling pathway in experimental stroke. Neuroscience. 2013;230:157–71.PubMedGoogle Scholar
  60. Rolin D. Metabolomics coming of age with its technological diversity, vol. 67. Oxford: Academic; 2012.Google Scholar
  61. Romagnolo DF, Selmin OI. Flavonoids and cancer prevention: a review of the evidence. J Nutr Gerontol Geriatr. 2012;31(3):206–38.PubMedGoogle Scholar
  62. Safarzadeh E, Shotorbani SS, Baradaran B. Herbal medicine as inducers of apoptosis in cancer treatment. Adv Pharm Bull. 2014;4(Suppl 1):421.PubMedPubMedCentralGoogle Scholar
  63. Saqib U, Sarkar S, Suk K, et al. Phytochemicals as modulators of M1-M2 macrophages in inflammation. Oncotarget. 2018;9(25):17937–50.PubMedPubMedCentralGoogle Scholar
  64. Sies H, Schewe T, Heiss C, et al. Cocoa polyphenols and inflammatory mediators. Am J Clin Nutr. 2005;81(1):304S–12S.PubMedGoogle Scholar
  65. Sirois P, Saura C, Salari H, et al. Comparative effects of etodolac, indomethacin, and benoxaprofen on icosanoid biosynthesis. Inflammation. 1984;8(4):353–6.PubMedGoogle Scholar
  66. Siu D. Natural products and their role in cancer therapy. Med Oncol. 2011;28(3):888–900.PubMedGoogle Scholar
  67. Song Y, Dou H, Gong W, et al. Bis-N-norgliovictin, a small-molecule compound from marine fungus, inhibits LPS-induced inflammation in macrophages and improves survival in sepsis. Eur J Pharmacol. 2013;705:49–60.PubMedGoogle Scholar
  68. Surh Y-J. Cancer chemoprevention with dietary phytochemicals. Nat Rev Cancer. 2003;10:768–80.Google Scholar
  69. Suzuki K, Yahara S, Hashimoto F, et al. Inhibitory activities of (-)-epigallocatechin-3-O-gallate against topoisomerases I and II. Biol Pharm Bull. 2001;24(9):1088–90.PubMedGoogle Scholar
  70. Takimoto CH, Wright J, Arbuck SG. Clinical applications of the camptothecins. Biochim Biophys Acta (BBA)-Gene Struct Expr. 1998;1400(1–3):107–19.Google Scholar
  71. Thoppil RJ, Bishayee A. Terpenoids as potential chemopreventive and therapeutic agents in liver cancer. World J Hepatol. 2011;3(9):228.PubMedPubMedCentralGoogle Scholar
  72. Tomicic MT, Kaina B. Topoisomerase degradation, DSB repair, p53 and IAPs in cancer cell resistance to camptothecin-like topoisomerase I inhibitors. Biochim Biophys Acta (BBA)-Rev Cancer. 2013;1835(1):11–27.Google Scholar
  73. Vasanthi HR, ShriShriMal N, Das DK. Phytochemicals from plants to combat cardiovascular disease. Curr Med Chem. 2012;19(14):2242–51.PubMedGoogle Scholar
  74. Wang W, Hu Y. Small molecule agents targeting the p53-MDM2 pathway for cancer therapy. Med Res Rev. 2012;32(6):1159–96.PubMedGoogle Scholar
  75. Wang G, Tang W, Bidigare RR. Terpenoids as therapeutic drugs and pharmaceutical agents. In: Natural products. Totowa: Humana Press; 2005. p. 197–227.Google Scholar
  76. Wang S, Meckling KA, Marcone MF, et al. Can phytochemical antioxidant rich foods act as anti-cancer agents? Food Res Int. 2011;44(9):2545–54.Google Scholar
  77. Wang S, Su R, Nie S, et al. Application of nanotechnology in improving bioavailability and bioactivity of diet-derived phytochemicals. J Nutr Biochem. 2014;25(4):363–76.PubMedGoogle Scholar
  78. Weaver BA. How Taxol/paclitaxel kills cancer cells. Mol Biol Cell. 2014;25(18):2677–81.PubMedPubMedCentralGoogle Scholar
  79. Westerterp M, Gautier EL, Ganda A, et al. Cholesterol accumulation in dendritic cells links the inflammasome to acquired immunity. Cell Metab. 2017;25(6):1294–304.PubMedPubMedCentralGoogle Scholar
  80. Xie J, Yang Z, Zhou C, et al. Nanotechnology for the delivery of phytochemicals in cancer therapy. Biotechnol Adv. 2016;34(4):343–53.PubMedGoogle Scholar
  81. Yang H, Ping Dou Q. Targeting apoptosis pathway with natural terpenoids: implications for treatment of breast and prostate cancer. Curr Drug Targets. 2010;11(6):733–44.PubMedPubMedCentralGoogle Scholar
  82. Yang X, Xu S, Qian Y, et al. Resveratrol regulates microglia M1/M2 polarization via PGC-1α in conditions of neuroinflammatory injury. Brain Behav Immunol. 2017;64:162–72.Google Scholar
  83. Zhu Y, Li X, Chen J, et al. The pentacyclic triterpene Lupeol switches M1 macrophages to M2 and ameliorates experimental inflammatory bowel disease. Int Immunopharmacol. 2016;30:74–84.PubMedGoogle Scholar
  84. Ziegler RG, Colavito EA, Hartge P, et al. Importance of α-carotene, β-carotene, and other phytochemicals in the etiology of lung cancer. J Natl Cancer Inst. 1996;88(9):612–5.PubMedGoogle Scholar

Copyright information

© Springer Nature Singapore Pte Ltd. 2019

Authors and Affiliations

  • Nidhi Sharma
    • 1
  • Herschel S. Dhekne
    • 2
  • Sabyasachi Senapati
    • 1
  1. 1.Department of Human Genetics and Molecular MedicineCentral University of PunjabBathindaIndia
  2. 2.Department of BiochemistryStanford UniversityStanfordUSA

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