Biological Trace Element Research

, Volume 182, Issue 2, pp 265–277 | Cite as

Role of Vital Trace Elements in Nanocurcumin-Centered Formulation: A Novel Approach to Resuscitate the Immune System

  • Mahendra Kumar Trivedi
  • Mayank Gangwar
  • Sambhu Charan Mondal
  • Snehasis JanaEmail author


The present paper described the immunomodulatory potential of novel nanocurcumin-based formulation enriched with trace elements and vitamins on cyclophosphamide-induced immunosuppression in rat model. Major immune-related assays were monitored such as hemagglutination assay, delayed-type hypersensitivity (DTH) reaction, cellular immune response, IgG, IgE, IgM, cerebrospinal fluid biomarkers, hematological study, antioxidant profile, and lipid biomarkers. Chemical characterization of novel formulation showed retention time (R t ) 18.98 of curcumin, while LC-MS data revealed the presence of the curcumin mass at m/z 369.01 [M + H]+ (calculated for C21H21O6 +, 369.13). This novel formulation exhibited significantly (p ≤ 0.001) increased primary and secondary antibody titer by 72.41% and 33.25%, respectively, while DTH response being improved by 87.50% (p ≤ 0.01). However, CD4+, CD8+, and CD28+ counts were significantly (p ≤ 0.05) increased by 76.46%, 68.21%, and 19.29%, respectively, while the concentrations of IgE, IgM, and IgG were significantly (p ≤ 0.05) increased by 40%, 28.43%, and 38.75%, respectively. CSF biomarkers analysis showed a decreased level of corticosterone, dopamine, serotonin, and tau protein by 29.38%, 51.73%, 29.93%, and 4.87%, respectively. Antioxidant enzymes such as CAT, GPx, and SOD were increased by 43.74%, 49.00%, and 40.84%, respectively, and non-enzymatic component, GSH, was increased by 55.52%. Similarly, free radical LPO was significantly (p ≤ 0.05) decreased by 40.37%, and acute inflammatory marker, MPO concentration, was reduced by 31.14%, compared with the disease control group. In addition, supportive hematology and lipid profile analysis showed promising results with improved overall animal profile. Thus, trace elements in novel formulation can be used in the various pharmacological activities and as dietary supplement due to its wide properties.


Nanocurcumin Immunomodulation Antioxidant activity Free radical scavenging Cellular and humoral immunity CSF biomarkers 



The authors are grateful to the support of Trivedi Science, Trivedi Global, Inc., and Trivedi Master Wellness throughout the work.

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.


  1. 1.
    Cooper MD, Schroeder HW (2005) Primary immune deficiency diseases. In: Harrison TR, editor. Harrison’s principles of internal medicine, vol 1939-1941. Mc Graw-Hill, New York, p 16Google Scholar
  2. 2.
    Calder PC, Field CJ, Gill HS (2003) Nutrition and immune function. Br J Nutr 90:239–241CrossRefGoogle Scholar
  3. 3.
    Iwu MM, Jackson JE, Schuster BG (1994) Medicinal plants in the fight against leishmaniasis. Parasitol Today 10:6568CrossRefGoogle Scholar
  4. 4.
    Phillipson JD (1994) Natural products as drugs. Trans R Soc Trop Med Hyg 88:17–19CrossRefGoogle Scholar
  5. 5.
    Cooper EL (2004) Complementary and alternative medicine when rigorous can be science. Evid based complement. Alternat Med 1:1–4Google Scholar
  6. 6.
    Wijenayake A, Pitawala A, Bandara R, Abayasekara C (2014) The role of herbometallic preparations in traditional medicine—a review on mica drug processing and pharmaceutical applications. J Ethnopharmacol 155:1001–1010CrossRefPubMedGoogle Scholar
  7. 7.
    Venkatalakshmi P, Vadivel V, Brindha P (2016) Role of phytochemicals as immunomodulatory agents: a review. Int J Green Pharm 10(1):1–18CrossRefGoogle Scholar
  8. 8.
    Bhaumik S, Jyothi MD, Khar A (2000) Differential modulation of nitric oxide production by curcumin in host macrophages and NK cells. FEBS Lett 483:78–82CrossRefPubMedGoogle Scholar
  9. 9.
    Surh YJ, Chun KS, Cha HH, Han SS, Keum YS, Park KK, Lee SS (2001) Molecular mechanisms underlying chemopreventive activities of anti-inflammatory phytochemicals: down-regulation of COX-2 and iNOS through suppression of NF-κB activation. Mutat Res 481:243–268CrossRefGoogle Scholar
  10. 10.
    Goel A, Jhurani S, Aggarwal BB (2008) Multi-targeted therapy by curcumin: how spicy is it? Mol Nutr Food Res 52:1010–1030CrossRefPubMedGoogle Scholar
  11. 11.
    Hsu CH, Cheng AL (2007) Clinical studies with curcumin. Adv Exp Med Biol 595:471–480CrossRefPubMedGoogle Scholar
  12. 12.
    Tonnesen HH (2002) Solubility, chemical and photochemical stability of curcumin in surfactant solutions. Studies of curcumin and curcuminoids, XXVIII. Pharmazie 57:820–824PubMedGoogle Scholar
  13. 13.
    Gupta SC, Patchva S, Koh W, Aggarwal BB (2012) Discovery of curcumin, a component of golden spice, and its miraculous biological activities. Clin Exp Pharmacol Physiol 39(3):283–299CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Mora JR, Iwata M, von Andrian UH (2008) Vitamin effects on the immune system: vitamins A and D take centre stage. Nat Rev Immunol 8(9):685–698CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Lukác N, Massányi P (2007) Effects of trace elements on the immune system. Epidemiol Mikrobiol Imunol 56:3–9PubMedGoogle Scholar
  16. 16.
    Zebib B, Mouloungui Z, Noirot V (2010) Stabilization of curcumin by complexation with divalent cations in glycerol/water system. Bioinorg Chem Appl 2010:8CrossRefGoogle Scholar
  17. 17.
    Priyadarsini KI (2014) The chemistry of curcumin: from extraction to therapeutic agent. Molecules 19:20091–20112CrossRefPubMedGoogle Scholar
  18. 18.
    Ladics GS (2007) Primary immune response to sheep red blood cells (SRBC) as the conventional T-cell dependent antibody response (TDAR) test. J Immunotoxicol 4:149–152CrossRefPubMedGoogle Scholar
  19. 19.
    Nelson DA, Mildenhall P (1967) Studies on cytophilic antibodies. The production by mice of macrophage cytophilic antibodies to sheep erythrocytes: relationship to the production of other antibodies and development of delayed type hypersensitivity. Aust J Exp Bio Med Sci 45:113–120CrossRefGoogle Scholar
  20. 20.
    Shinde UA, Phadke AS, Nair AM, Mungantiwar AA, Dikshit VS, Saraf MM (1999) Preliminary studies on the immunomodulatory activity of Cedrus deodara wood oil. Fitoterapia 79:333–339CrossRefGoogle Scholar
  21. 21.
    Trivedi MK, Gangwar M, Mondal SC, Jana S (2017) Immunomodulatory properties and biomarkers characterization of novel Withania somnifera based formulation supplemented with minerals in Sprague Dawley rats. Orient Pharm Exp Med 17:59–69CrossRefGoogle Scholar
  22. 22.
    Wang L-S, Leung YY, Chang S-K, Leight S, Knapik-Czajka M, Baek Y, Shaw LM, Lee VM-Y, Trojanowski JQ, Clark CM (2013) Comparison of xMAP and ELISA assays for detecting CSF biomarkers of Alzheimer’s disease. J Alzheimers Dis 31(2):439–445Google Scholar
  23. 23.
    Vieira TO, Seifriz I, Charão CCT, de Oliveira SQ, Creczynski-Pasa TB (2011) Antioxidant effects of crude extracts from Baccharis species: inhibition of myeloperoxidase activity, protection against lipid peroxidation, and action as oxidative species scavenger. Rev Bras 21(4):601–607Google Scholar
  24. 24.
    Feldman BF, Zinkl JG, Jain VC (2000) Laboratory techniques for avian hematology in Schalm’s veterinary hematology, 5th edn. Lippincott Williams & Wilkins, TorontoGoogle Scholar
  25. 25.
    Dhawan BN, Srimal RC (1980) India: United Nations Industrial Development Organization and International Center for Science and High Technology; Acute toxicity and gross effects. In: Laboratory Manual for Pharmacological Evaluation of Natural Products; pp. 17–20.Google Scholar
  26. 26.
    Ramalingam P, Ko YT (2014) A validated LC-MS/MS method for quantitative analysis of curcumin in mouse plasma and brain tissue and its application in pharmacokinetic and brain distribution studies. J Chromatogr B Analyt Technol Biomed Life Sci 969:101–108CrossRefPubMedGoogle Scholar
  27. 27.
    Pandit RS, Gaikwad SC, Agarkar GA, Gade AK, Rai M (2015) Curcumin nanoparticles: physico-chemical fabrication and its in vitro efficacy against human pathogens. 3. Biotech 5(6):991–997Google Scholar
  28. 28.
    Anand P, Kunnumakkara A, Newman R, Aggarwal B (2007) Bioavailability of curcumin: problems and promises. Mol Pharma 4(6):807–818CrossRefGoogle Scholar
  29. 29.
    Bhavana B, Buttar H, Jain V, Jain N (2011) Curcumin nanoparticles: preparation, characterization, and antimicrobial study. J Agri Food Chem 59:2056–2061CrossRefGoogle Scholar
  30. 30.
    Aranow C (2011) Vitamin D and the immune system. J Investig Med 59(6):881–886CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    Ströhle A, Hahn A (2009) Vitamin C and immune function. Med Monatsschr Pharm 32(2):49–54 quiz 55-6PubMedGoogle Scholar
  32. 32.
    Girodon F, Galan P, Monget AL, Boutron-Ruault MC, Brunet-Lecomte P, Preziosi P, Arnaud J, Manuguerra JC, Herchberg S (1999) Impact of trace elements and vitamin supplementation on immunity and infections in institutionalized elderly patients: a randomized controlled trial. MIN. VIT. AOX. Geriatric network. Arch Intern Med 159:748–754CrossRefPubMedGoogle Scholar
  33. 33.
    Chandra RK (1992) Effect of vitamin and trace-element supplementation on immune responses and infection in elderly subjects. Lancet 340:1124–1127CrossRefPubMedGoogle Scholar
  34. 34.
    Sempertegui F, Estrella B, Correa E, Aguirre L, Saa B, Torres M, Navarrete F, Alarcón C, Carrión J, Rodríguez GJK (1996) Effects of short-term zinc supplementation on cellular immunity, respiratory symptoms, and growth of malnourished Equadorian children. Eur J Clin Nutr 50:42–46PubMedGoogle Scholar
  35. 35.
    Field CJ, Johnson IR, Schley PD (2002) Nutrients and their role in host resistance to infection. J Leukoc Biol 71:16–32PubMedGoogle Scholar
  36. 36.
    Moriguchi S, Itoh T (1997) Vitamin E enhances T cell differentiation through increased epithelial cell function in rat thymus. Nutr Res 17:873–883CrossRefGoogle Scholar
  37. 37.
    McKenzie RC, Rafferty TS, Beckett GJ (1998) Selenium: an essential element for immune function. Immunol Today 19:342–345CrossRefPubMedGoogle Scholar
  38. 38.
    Kang BY, Song YJ, Kim K-M, Choe YK, Hwang SY, Kim TS (1999) Curcumin inhibits Th1 cytokine profile in CD4+ T cells by suppressing interleukin-12 production in macrophages. Br J Pharmacol 128(2):380–384CrossRefPubMedPubMedCentralGoogle Scholar
  39. 39.
    Dale MM, Forman JC (1989) Textbook of immunopharmacology (2ndedn). Blackwell and Scientific Publication, OxfordGoogle Scholar
  40. 40.
    Zhao SJ, Sun FJ, Tian EJ, Chen ZP (2008) The effects of iodine/selenium on the function of antigen presentation of peritoneal macrophages in rats. Zhonghua Yu Fang Yi Xue Za Zhi 42(7):485–488PubMedGoogle Scholar
  41. 41.
    Shaik-Dasthagirisaheb YB, Varvara G, Murmura G, Saggini A, Caraffa A, Antinolfi P, Tete’ S, Tripodi D, Conti F, Cianchetti E, Toniato E, Rosati M, Speranza L, Pantalone A, Saggini R, Tei M, Speziali A, Conti P, Theoharides TC, Pandolfi F (2013) Role of vitamins D, E and C in immunity and inflammation. J Biol Regul Homeost Agents 27(2):291–295PubMedGoogle Scholar
  42. 42.
    Miceli MC, Parnes JR (1991) The roles of CD4 and CD8 in T cell activation. Semin Immunol 3:133–141PubMedGoogle Scholar
  43. 43.
    Otuechere CA, Abarikwu SO, Olateju VI, Animashaun AL, Kale OE (2014) Protective effect of curcumin against the liver toxicity caused by propanil in rats. Int Sch Res Notices 2014:8Google Scholar
  44. 44.
    Farvid MS, Siassi F, Jalali M, Hosseini M, Saadat N (2004) The impact of vitamin and/or mineral supplementation on lipid profiles in type 2 diabetes. Diabetes Res Clin Pract 65(1):21–28CrossRefPubMedGoogle Scholar
  45. 45.
    Conforti F, Sosa S, Marrelli M, Menichini F, Statti GA, Uzunov D, Tubarob A, Menichinia F (2009) The protective ability of Mediterranean dietary plants against the oxidative damage: the role of radical oxygen species in inflammation and the polyphenol, flavonoid and sterol contents. Food Chem 112:587–594CrossRefGoogle Scholar
  46. 46.
    Carvalho DM, Takeuchi KP, Geraldine RM, Moura CJ, Torres MCL (2015) Production, solubility and antioxidant activity of curcumin nanosuspension. Food Sci Technol (Campinas) 35(1):115–119CrossRefGoogle Scholar
  47. 47.
    Aluise CD, Sowell RA, Butterfield DA (2008) Peptides and proteins in plasma and cerebrospinal fluid as biomarkers for the prediction, diagnosis, and monitoring of therapeutic efficacy of Alzheimer’s disease. Biochim Biophys Acta 1782(10):549–558CrossRefPubMedPubMedCentralGoogle Scholar
  48. 48.
    Blennow K, Hampel H, Weiner M, Zetterberg H (2010) Cerebrospinal fluid and plasma biomarkers in Alzheimer disease. Nat Rev Neurol 6(3):131–144CrossRefPubMedGoogle Scholar
  49. 49.
    Mishra S, Palanivelu K (2008) The effect of curcumin (turmeric) on Alzheimer’s disease: an overview. Ann Indian Acad Neurol 11(1):13–19CrossRefPubMedPubMedCentralGoogle Scholar
  50. 50.
    Swaminathan A, Jicha GA (2014) Nutrition and prevention of Alzheimer’s dementia. Front Aging Neurosci 6:282CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2017

Authors and Affiliations

  • Mahendra Kumar Trivedi
    • 1
  • Mayank Gangwar
    • 2
  • Sambhu Charan Mondal
    • 2
  • Snehasis Jana
    • 2
    Email author
  1. 1.Trivedi Global, Inc.HendersonUSA
  2. 2.Trivedi Science Research Laboratory Pvt. Ltd.BhopalIndia

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