Skip to main content

Advertisement

SpringerLink
Log in

Protective effect of Echinacea purpurea (Immulant) against cisplatin-induced immunotoxicity in rats

  • Research Article
  • Published:
DARU Journal of Pharmaceutical Sciences Aims and scope Submit manuscript

Abstract

Purpose

Cisplatin, one of the most effective anticancer drugs, is known to cause undesirable adverse effects, including immunotoxicity. Echinacea purpurea is an important medicinal plant with immunostimulatory and anti-inflammatory activities. We have investigated the protective effect of an herbal formulation (Immulant) containing E. purpurea extract against cisplatin-induced immunotoxicity in rats.

Methods

Forty mature albino rats were randomized into four groups (10 rats/group). Control (group 1) animals were subjected to intraperitoneal (i.p.) injection of saline solution (0.2 ml) once every 3 days. Group 2 animals received cisplatin (3.5 mg/kg, i.p.) once every 3 days for successive 2 weeks. Group 3 rats received oral Immulant (150 mg/kg) once daily for 2 weeks. Group 4 animals received oral Immulant treatment as in group 3 in addition to cisplatin as in group 2. Serum level of total protein and albumin, total and differential leukocytic count, phagocytic activity of monocytes, humoral activity and splenic histopathology and immunohistochemistry were used as diagnostic markers of immunotoxicity.

Results

Cisplatin induced marked inhibition of cellular immunity as exhibited by significant decrease of leukocytic count, lymphocyte percentage and phagocytic activity with marked increase in neutrophil percentage. Humoral immunity represented by marked inhibition in total protein and γ-globulin concentration and significant inhibition in antibody titer against Mycoplasma gallisepticum were recorded. Histopathological and immunohistochemical observation of the spleen of cisplatin-treated rats revealed obvious pathological findings of marked depletion and degeneration of lymphoid tissue. Co-oral administration of Immulant resulted in substantial improvement of various immunotoxicological indices compared to cisplatin control.

Conclusion

The herbal medicine Immulant is an immunostimulant which could be used to treat the immunotoxic effects of cisplatin.

Cisplatin (CP) is a highly effective antineoplastic DNA alkylating agent. CP induces free radical production causing an oxidative damage.Cisplatin induced marked inhibition in cellular and humoral immunityEchinacea purpurea (Immulant) is a powerful anticytotoxic agent against cisplatin toxicity.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Baek SM, Kwon CH, Kim JH, Woo JS, Jung JS, Kim YK. Differential roles of hydrogen peroxide and hydroxyl radical in cisplatin-induced cell death in renal proximal tubular epithelial cells. J Lab Clin Med. 2003;142:178–86.

    Article  CAS  PubMed  Google Scholar 

  2. Hasaaan I, Chibber S, Naseem I. Ameliorative effect of riboflavin on the cisplatin induced nephrotoxicity and hepatotoxicity under photoillumination. Food Chem Toxicol. 2010;48:2050–8.

    Google Scholar 

  3. Jordan P, Carmo-Fonseca M. Molecular mechanisms involved in cisplatin cytotoxicity. Cell Mol Life Sci. 2000;57:1229–35.

    Article  CAS  PubMed  Google Scholar 

  4. Zandvoort A, Lodewijk ME, Klok PA, Dammers PM, Kroese FG, Timens W. Slow recovery of follicular B cells and marginal zone B cells after chemotherapy: implications for humoral immunity. Clin Exp Immunol. 2001;124:172–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Onsrud M, Bosnes V, Grahm I. Cis-platinum as adjunctive to surgery in early stage ovarian carcinoma: effects on lymphoid cell subpopulations. Gynecol Oncol. 1986;23:323–8.

    Article  CAS  PubMed  Google Scholar 

  6. Lee TT, Chen CL, Shieh ZH, Lin JC, Yu B. Study on antioxidant activity of Echinacea purpurea L. extracts and its impact on cell viability. Afr J Biotechnol. 2009;8:5097–105.

    CAS  Google Scholar 

  7. Matthias A, Banbury L, Bone KM, Leach DN, Lehmann RP. Echinacea alkylamides modulate induced immune responses in T-cells. Fitoterapia. 2008;79:53–8.

    Article  CAS  PubMed  Google Scholar 

  8. Wang Y, Chen L, Huang G, He D, He J, Xu W, et al. Klotho sensitizes human lung Cancer cell line to cisplatin via PI3k/Akt pathway. PLoS One. 2013;8:573–91.

    Article  Google Scholar 

  9. Zhai Z, Liu Y, Wu L, Senchina DS, Wurtele ES, Murphy PA, et al. Enhancement of innate and adaptive immune functions by multiple Echinacea species. J Med Food. 2007;10:423–34.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Paget GE, Barnes JM. Toxicity tests. In: Laurence DR, Bachorach AL, editors. Evaluation of drug activities: Pharmacomertrics. New York: Academic Press; 1964. p. 133–66.

    Google Scholar 

  11. Zink T, Chaffin J. Herbal ‘Health’ products: what family physicians need to know. Am Fam Physician. 1998;58:1133–40.

    CAS  PubMed  Google Scholar 

  12. Schalm OW, Jain NE, Caroll EJ. Veterinary haematology. 3rd ed. Philadelphia: Lea and Febiger; 1975.

    Google Scholar 

  13. Gornall AG, Bardawill CJ, David MM. Determination of serum proteins by means of the biuret reaction. J Biol Chem. 1949;177:751–66.

    CAS  PubMed  Google Scholar 

  14. Doumas BT, Watson WA, Biggs HG. Albumin standards and the measurement of serum albumin with bromcresol green. Clin Chim Acta. 1971;31:87–96.

    Article  CAS  PubMed  Google Scholar 

  15. Kaplan A, Saveloy J. Evaluation of a cellulose-acetate electrophoresis system for serum fractionation. Clin Chem. 1965;11:937.

    CAS  PubMed  Google Scholar 

  16. Anthony TWC, Twin KML, Erin MW, Michael EM. Phagocytic and killing capacities of uterine derived leukocytes from mares resistant and susceptible to chronic endometritis. Am J Vet Res. 1985;46:1938–40.

    Google Scholar 

  17. Chu Y, Dietert RR. Monocyte function in chicken with hereditary dystrophy. J Poult Sci. 1989;68:226–32.

    Article  CAS  Google Scholar 

  18. Boyum A. Isolation of mononuclear cells and granulocytes from human blood. Scand J Clin Lab Invest Suppl. 1968;21:77–89.

    Article  CAS  Google Scholar 

  19. Hanks DH, Waalace OH. Determination of cell viability. Proc Soc Exp Biol Med. 1985;98:183–92.

    Google Scholar 

  20. Bancroft JD, Gamble M. Theory and practice of histological techniques. 6th ed. Edinburgh, London and New York: Churchill Livingston; 2007.

    Google Scholar 

  21. Ramos-Vara JA. Technical aspects of immunohistochemistry. Vet Pathol. 2005;42:405–26.

    Article  CAS  PubMed  Google Scholar 

  22. Wijermans PW, Gerrits WB, Haak HL. Severe immunodeficiency in patients treated with fludarabine monophosphate. Eur J Haematol. 1993;50:292–6.

    Article  CAS  PubMed  Google Scholar 

  23. Park KP, Lee BC, Lee JS, Cho MH. Angelica gigas Nakai extract ameliorates the effects of cyclophosphamide on immunological and hematopoietic dysfunction in mice. J Med Plant Res. 2014;8:657–63.

    Article  CAS  Google Scholar 

  24. Awadallah AM, Moussa FI, Abad El Hameed N. Treatment of cisplatin Haematotoxicity with Lasix or selenium or both in adult male rabbits. Pak J Biol Sci. 2001;4:89–93.

    Article  Google Scholar 

  25. Pieretti M, Hopenhayn-Rich C, Khattar NH, Cao Y, Huang B, Tucker TC. Heterogeneity of ovarian cancer: relationships among histological group, stage of disease, tumor markers, patient characteristics, and survival. Cancer Investig. 2002;20:11–23.

    Article  Google Scholar 

  26. Gale RP. Antineoplastic chemotherapy myelosuppression: mechanisms and new approaches. Exp Hematol. 1985;13:3–7.

    CAS  PubMed  Google Scholar 

  27. Markovic SD, Zˇizic JB, Djacic DS, Obradovic AD, MG C’u, Cvetkovic DM, et al. Alteration of oxidative stress parameters in red blood cells of rats after chronic in vivo treatment with cisplatin and selenium. Arch Biol Sci. 2011;63:991–9.

    Article  Google Scholar 

  28. Bhoopendra K, Nitesh K. Immunotoxicity of lambda-Cyhalothrin in Wistar albino rats. International Journal of Toxicological and Pharmacological Research. 2014;6:47–56.

    Google Scholar 

  29. Jílek P, Dvoráková J, Turecková J, Procházková J. The effect of platinum cytostatics on delayed-type hypersensitivity in mice. Neoplasma. 1989;36:659–65.

    PubMed  Google Scholar 

  30. Li XB, Schluesener HJ. Therapeutic effects of cisplatin on rat experimental autoimmune encephalomyelitis. Arch Immunol Ther Exp. 2006;54:51–3.

    Article  CAS  Google Scholar 

  31. Kouchi Y, Maeda Y, Ohuchida A, Ohsawa M. Immunotoxic effect of low dose cisplatin in mice. J Toxicol Sci. 1996;21:227–33.

    Article  CAS  PubMed  Google Scholar 

  32. Hegab S, MutawaS A. Immunopathogenesis of Bebeet′s disease. Clin Immunol. 2000;96:174–86.

    Article  CAS  PubMed  Google Scholar 

  33. Kuper CF, Schuurman HJ, Vos JG. Pathology in immunotoxicology. In: Burleson GR, Dean JH, Munson AE, editors. Methods in immunotoxicology. New York: Wiley-Liss; 1995. p. 397–436.

    Google Scholar 

  34. Kuper CF, Harleman JH, Richter-Reichhelm HB, Vos JG. Histopathologic approaches to detect changes indicative of immunotoxicity. Toxicol Pathol. 2000;28:454–66.

    Article  CAS  PubMed  Google Scholar 

  35. Kuper CF, deHeer E, Van Loveren H, Vox JG. Immune system. In: Haschek W, Rousseaux CG, Wallig MA, editors. Handbook of toxicological pathology. San Diego: Academic Press; 2002. p. 585–646.

    Google Scholar 

  36. Descotes J. Methods of evaluating immunotoxicity. Expert Opin Drug Metab Toxicol. 2006;2:249–59.

    Article  CAS  PubMed  Google Scholar 

  37. Pearse G, Pietersma A, Cunliffe J, Foster JR, Turton J, Derbyshire N, et al. Time-course study of the immunotoxic effects of the anticancer drug chlorambucil in the rat. Toxicol Pathol. 2009;37:887–901.

    Article  CAS  PubMed  Google Scholar 

  38. Monfared AL, Jaafari A, Sheibani M. Histological and histometrical evidences for phenol immunotoxicity in mice. Comp Clin Pathol. 2014;23:529–53.

    Article  CAS  Google Scholar 

  39. Menezes SL, Bozza PT, Neto HC, Laranjeira AP, Negri EM, Capelozzi VL, et al. Pulmonary and extrapulmonary acute lung injury: inflammatory and ultrastructural analyses. J Appl Physiol. 2005;98:1777–83.

    Article  PubMed  Google Scholar 

  40. Crăciun C, Paşca C. Structural and ultrastructural data on side effects of cisplatin in spleen, kidney and liver of rats. Acta Metallomica – MEEMB. 2014;11:9–22.

    Google Scholar 

  41. Tuorkey MJ. Cancer therapy with phytochemicals: present and future perspectives. Biomed Environ Sci. 2015;28:808–19.

    Article  PubMed  Google Scholar 

  42. Liang B, Wang S, Ye YJ, Yang XD, Wang YL, Qu J, et al. Impact of postoperative omega-3 fatty acid-supplemented parenteral nutrition on clinical outcomes and immunomodulations in colorectal cancer patients. World J Gastroenterol. 2008;14:2434–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Mantovani MS, Bellini MF, Angeli JP, Oliveira RJ, Silva AF, Ribeiro LR. Beta-glucans in promoting health: prevention against mutation and cancer. Mutat Res. 2008;658:154–61.

    Article  CAS  PubMed  Google Scholar 

  44. Badhani B, Sharma N, Kakkar R. Gallic acid: a versatile antioxidant with promising therapeutic and industrial applications. RSC Advances. 2015;5:27540–57.

    Article  CAS  Google Scholar 

  45. Barrett B. Medicinal properties of Echinacea: a critical review. Phytomedicine. 2003;10:66–86.

    Article  CAS  PubMed  Google Scholar 

  46. Cundell DR, Matrone MA, Ratajczak P, Pierce JD Jr. The effect of aerial parts of Echinacea on the circulating white cell levels and selected immune functions of the aging male Sprague-Dawley rat. Int Immunopharmacol. 2003;3:1041–8.

    Article  CAS  PubMed  Google Scholar 

  47. Kim LS, Waters RF, Burkholder PM. Immunological activity of larch arabinogalactan and Echinacea: a preliminary, randomized, double-blind, placebo-controlled trial. Altern Med Rev. 2002;7:138–49.

    PubMed  Google Scholar 

  48. Echinacea BR. Biological effects and active principals, phytomedicines of Europe: chemistry and biological activity. In: Lawson LD, Bauer R, editors. ACS symposium series, vol. 691. Washington, DC: American Chemical Society; 1998. p. 140–57.

    Google Scholar 

  49. Chen Y, Fu T, Tao T, Yang I, Chang Y, Kim L. Macrophage activating effect of new alkamides from the roots of Echinacea species. J Nat Prod. 2005;68:773–6.

    Article  CAS  PubMed  Google Scholar 

  50. Merali S, Bnns S, Paulin-Levasseur M, Ficker C, Smith M, Baum BR. Antifungal and anti-inflammatory activity of the genus Echinacea. Pharm Biol. 2003;41:412–20.

    Article  CAS  Google Scholar 

  51. Wills RB, Bone K, Morgan M. Herbal products: active constituents, modes of action and quality control. Nutr Res Rev. 2000;13:47–77.

    Article  CAS  PubMed  Google Scholar 

  52. Thygesen L, Thulin J, Mortensen A, Skibsted LH, Molgaard P. Antioxidant activity of cichoric acid and alkamides from Echinacea purpurea, alone and in combination. Food Chem. 2007;101:74–81.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

The authors express their sincere thanks to Prof. Sheren Ghalebfor review of the manuscript.

Author information

Authors and Affiliations

  1. Department of Toxicology and Forensic Medicine, Faculty of Veterinary Medicine, Cairo University, Cairo, Egypt

    Abdelazeem Ali Khalaf & Adel Fathy Tohamy

  2. Department of Cytology and Histology, Faculty of Veterinary Medicine, Cairo University, Cairo, Egypt

    Shaymaa Hussein

  3. Department of Microbiology, Faculty of Veterinary Medicine, Cairo University, Cairo, Egypt

    Sherif Marouf

  4. Department of Anatomy and Embryology, Faculty of Medicine, Beni-Suef University, Beni-Suef, Egypt

    Hanan Dawood Yassa

  5. Department of Forensic Medicine and Clinical Toxicology, Faculty of Medicine, Beni-Suef University, Beni-Suef, Egypt

    Amr Reda Zaki

  6. Lake Erie College of Osteopathic Medicine, 5000 Lakewood Ranch Boulevard, Bradenton, FL, 34211, USA

    Anupam Bishayee

Authors
  1. Abdelazeem Ali Khalaf
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Shaymaa Hussein
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Adel Fathy Tohamy
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Sherif Marouf
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Hanan Dawood Yassa
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Amr Reda Zaki
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Anupam Bishayee
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

All authors participated in the design, interpretation of the study, analysis of the data, and review of the manuscript.

Corresponding authors

Correspondence to Amr Reda Zaki or Anupam Bishayee.

Ethics declarations

Ethics approval

All animal studies were performed in accordance with the procedure approved by the Institutional Animal Care and Use Committee of Cairo University (IACUC, CU-II-F-10-19).

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interest.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Khalaf, A.A., Hussein, S., Tohamy, A.F. et al. Protective effect of Echinacea purpurea (Immulant) against cisplatin-induced immunotoxicity in rats. DARU J Pharm Sci 27, 233–241 (2019). https://doi.org/10.1007/s40199-019-00265-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40199-019-00265-4

Keywords

Search

Navigation