Skip to main content
SpringerLink
Log in

Carica papaya ameliorates thrombocytopenia through upregulation of Interleukin-11 and modulation of thrombopoietin in mouse model of carboplatin-induced myelosuppression

  • Original Article
  • Published:
Molecular Biology Reports Aims and scope Submit manuscript

Abstract

Introduction

Carica papaya L. (C. papaya) is used as a folk medicine for the treatment of various diseases throughout the world. Recently, papaya leaves decoction has been effectively used for the prevention and treatment of thrombocytopenia. The current study was undertaken to evaluate the thrombopoietic and immunomodulatory activities of C. papaya leaves in the mouse model of carboplatin induced myelosuppression.

Methods

Myelosuppression was induced by a single intraperitoneal injection of carboplatin (125 mg/kg b. w.). Aqueous extract of C. papaya leaves (15 mg/kg b. w.) was given orally by feeding tube from day 0–18 to preventive group to see the preventive effect and from day 6–18 to treatment group for treatment effect.

Results

The results showed that the C. papaya leaves extract significantly decreased the fall in platelet count in preventive and treatment groups. Extract significantly prevented the fall in total WBCs count on day 12 and 18 in the preventive group, whereas it significantly elevated the WBCs count in treatment group on day 18. Significantly increased RBCs count in both groups was observed on day 18 after treatment with C. papaya leaves extract. Treatment with C. papaya leaves extract significantly upregulated the mRNA expression levels of thrombopoietic cytokine IL-11 in both preventive and treatment groups. It is also observed that restoration of normal platelet count might have been resulted owing to the synergistic effect of upregulated IL-11 which ultimately led to a significantly diminished TPO expression.

Conclusion

Our data suggest that aqueous extract of C. papaya leaves possesses significant preventive and curative properties against thrombocytopenia.

Graphical abstract

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
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Raadsen M, Du Toit J, Langerak T, van Bussel B, van Gorp E, Goeijenbier M (2021) Thrombocytopenia in virus infections. J Clin Med 10(4):877

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Bonadies N, Rovó A, Porret N, Bacher U (2021) When should we think of myelodysplasia or bone marrow failure in a thrombocytopenic patient? A practical approach to diagnosis. J Clin Med 10(5):1026

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Blumberg N, Heal JM, Phillips GL (2010) Platelet transfusions: trigger, dose, benefits, and risks. F1000 Med Rep 2:5

    Article  PubMed  PubMed Central  Google Scholar 

  4. Obeagu EI, Okoroiwu IL, Obeagu GU. (2022). Relationship between Thrombopoietin and Interleukin 3: A Review. Int J Curr Res Chem Pharm. Sci. 9(1):7–13.

  5. Bedet A, Razazi K, Boissier F, Surenaud M, Hue S, Giraudier S, Brun-Buisson C, Mekontso DA (2018) Mechanisms of thrombocytopenia during septic shock: a multiplex cluster analysis of endogenous sepsis mediators. Shock 49(6):641–648

    Article  PubMed  Google Scholar 

  6. Tiedt R, Coers J, Ziegler S, Wiestner A, Hao-Shen H, Bornmann C, Schenkel J, Karakhanova S, de Sauvage FJ, Jackson CW, Skoda RC (2009) Pronounced thrombocytosis in transgenic mice expressing reduced levels of Mpl in platelets and terminally differentiated megakaryocytes. Blood 113(8):1768–1777

    Article  CAS  PubMed  Google Scholar 

  7. Bussel JB, Soff G, Balduzzi A, Cooper N, Lawrence T, Semple JW (2021) A review of romiplostim mechanism of action and clinical applicability. Drug Des Dev Ther 15:2243

    Article  Google Scholar 

  8. Behrens K, Alexander WS (2018) Cytokine control of megakaryopoiesis. Growth Factors 36(3–4):89–103

    Article  CAS  PubMed  Google Scholar 

  9. Xu DH, Zhu Z, Wakefield MR, Xiao H, Bai Q, Fang Y (2016) The role of IL-11 in immunity and cancer. Cancer Lett 373(2):156–163

    Article  CAS  PubMed  Google Scholar 

  10. Permyakov EA, Uversky VN, Permyakov SE (2016) Interleukin-11: a multifunctional cytokine with intrinsically disordered regions. Cell Biochem Biophys 74(3):285–296

    Article  CAS  PubMed  Google Scholar 

  11. Abdel-Razek AS, El-Naggar ME, Allam A, Morsy OM, Othman SI (2020) Microbial natural products in drug discovery. Processes 8(4):470

    Article  CAS  Google Scholar 

  12. Ma RH, Ni ZJ, Zhu YY, Thakur K, Zhang F, Zhang YY, Hu F, Zhang JG, Wei ZJ (2021) A recent update on the multifaceted health benefits associated with ginger and its bioactive components. Food Funct 12(2):519–542

    Article  CAS  PubMed  Google Scholar 

  13. Vij T, Prashar Y (2015) A review on medicinal properties of Carica papaya Linn. Asian Pac J Trop Dis 5(1):1–6

    Article  Google Scholar 

  14. Madjos GG, Luceño AM (2019) Comparative cytotoxic properties of two varieties of Carica papaya leaf extracts from Mindanao, Philippines using brine shrimp lethality assay. BEPLS 8(2):113–118

    Google Scholar 

  15. Saraf M, Kavimandan B (2017) Animal trials of Carica papaya leaf extracts for increasing platelet count. Indian J Public Health Res Dev 8(4):782–787

    Article  Google Scholar 

  16. Jayasinghe CD, Gunasekera DS, De Silva N, Jayawardena KK, Udagama PV (2017) Mature leaf concentrate of Sri Lankan wild type Carica papaya Linn. modulates nonfunctional and functional immune responses of rats. BMC Complementary Altern Med. 17(1):1–4

    Article  Google Scholar 

  17. Thomas AA, Kuruvillia MA (2017) Effectiveness of caripill drug in the treatment of dengue fever. World J Pharm Res 6(7):1658–1681

    Article  CAS  Google Scholar 

  18. Mahmood AA, Sidik K, Salmah I (2005) Wound healing activity of Carica papaya L. aqueous leaf extract in rat. Int J Mol Med Adv Sci 4:398–401

    Google Scholar 

  19. Tahir N, Zaheer Z, Kausar S, Chiragh S (2014) Prevention of fall in platelet count by Carica papaya leaf juice in carboplatin induced thrombocytopenia in mice. Biomedica 30(1):21–25

    Google Scholar 

  20. Shahzad M, Yang X, Asim Raza MB, Sun Q, Han Y, Zhang F, Cao Y, Lu S (2009) Black seed oil ameliorates allergic airway inflammation by inhibiting T-cell proliferation in rats. Pulm Pharmacol Ther 22:37–43

    Article  CAS  PubMed  Google Scholar 

  21. Sathasiva K, Ramanathan S, Mansor SM, Haris MR, Wernsdorfer WH (2009) Thrombocyte count in mice after the administration of papaya leaf suspension. Wien Klin Wochenschr 121:19–22

    Article  Google Scholar 

  22. Bobis S, Jarocha D, Majka M (2016) Mesenchymal stem cells: characteristics and clinical applications. Folia Histochem Cytobiol 44(4):215–230

    Google Scholar 

  23. Tahover E, Segal A, Isacson R, Rosengarten O, Grenader T, Gips M, Cherny N, Heching NI, Mesika L, Catane R, Gabizon A (2017) Dexrazoxane added to doxorubicin-based adjuvant chemotherapy of breast cancer: a retrospective cohort study with a comparative analysis of toxicity and survival. Anticancer Drugs 28(7):787–794

    Article  CAS  PubMed  Google Scholar 

  24. Weycker D, Hatfield M, Grossman A, Hanau A, Lonshteyn A, Sharma A, Chandler D (2019) Risk and consequences of chemotherapy-induced thrombocytopenia in US clinical practice. BMC Cancer 19(1):1–8

    Article  CAS  Google Scholar 

  25. Wu S, Zhang Y, Xu L, Dai Y, Teng Y, Ma S, Ho SH, Kim JM, Yu SS, Kim S, Song S (2012) Multicenter, randomized study of genetically modified recombinant human interleukin-11 to prevent chemotherapy-induced thrombocytopenia in cancer patients receiving chemotherapy. Support Care Cancer 20(8):1875–1884

    Article  PubMed  Google Scholar 

  26. Hou C, Yin M, Lan P, Wang H, Nie H, Ji X (2021) Recent progress in the research of Angelica sinensis (Oliv.) Diels polysaccharides: extraction, purification, structure and bioactivities. Chem Biol Technol 8(1):1–4

    Article  CAS  Google Scholar 

  27. Patil S, Shetty S, Bhide R, Narayanan S (2013) Evaluation of platelet augmentation activity of Carica papaya leaf aqueous extract in rats. J Pharmacogn Phytochem 1(5):57–60

    Google Scholar 

  28. McElroy PL, Wei P, Buck K, Sinclair AM, Eschenberg M, Sasu B, Molineux G (2015) Romiplostim promotes platelet recovery in a mouse model of multicycle chemotherapy-induced thrombocytopenia. Exp Hematol 43:479–487

    Article  CAS  PubMed  Google Scholar 

  29. Ochocinski D, Dalal M, Black LV, Carr S, Lew J, Sullivan K, Kissoon N (2020) Life-threatening infectious complications in sickle cell disease: a concise narrative review. Front Pediatr 8:1–22

    Article  Google Scholar 

  30. Gammulle A, Ratnasooriya WD, Jayakody JR, Fernando C, Kanatiwela C, Udagama PV (2012) Thrombocytosis and anti-inflammatory properties, and toxicological evaluation of Carica papaya mature leaf concentrate in a murine model. J Med Plants Res 1(2):21–30

    Google Scholar 

  31. Brigle K, Pierre A, Finley-Oliver E, Faiman B, Tariman JD, Miceli T (2017) Myelosuppression, bone disease, and acute renal failure. Clin J Oncol Nurs 21:60–76

    Article  PubMed  Google Scholar 

  32. Gammulle A, Ratnasooriya WD, Jayakody J, Fernando C, Kanatiwela C, Udagama PV (2012) Thrombocytosis and anti-inflammatory properties, and toxicological evaluation of Carica papaya mature leaf concentrate in a murine model. Int J Med Plant Res 1(2):21–30

    Google Scholar 

  33. Afdhal N, McHutchison J, Brown R, Jacobson I, Manns M, Poordad F, Weksler B, Esteban R (2008) Thrombocytopenia associated with chronic liver disease. J Hepatol 48(6):1000–1007

    Article  CAS  PubMed  Google Scholar 

  34. Suliman MI, Qayum I, Saeed F (2014) A randomized clinical trial of human interleukin-11 in dengue fever-associated thrombocytopenia. J Coll Phys Surg Pak 24(3):164–168

    Google Scholar 

  35. Kuter DJ (2015) Managing thrombocytopenia associated with cancer chemotherapy. Oncology 29(4):282

    PubMed  Google Scholar 

Download references

Funding

The authors have not disclosed any funding.

Author information

Authors and Affiliations

  1. Department of Pharmacology, University of Health Sciences, Lahore, Pakistan

    Sabeen Irshad, Arham Shabbir, Hina Aslam, Tasleem Akhtar & Muhammad Shahzad

Authors
  1. Sabeen Irshad
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Arham Shabbir
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Hina Aslam
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Tasleem Akhtar
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Muhammad Shahzad
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Muhammad Shahzad.

Ethics declarations

Conflict of interest

We wish to confirm that there are no known conflicts of interest associated with this publication and there has been no significant financial support for this work that could have influenced its outcome.

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

Irshad, S., Shabbir, A., Aslam, H. et al. Carica papaya ameliorates thrombocytopenia through upregulation of Interleukin-11 and modulation of thrombopoietin in mouse model of carboplatin-induced myelosuppression. Mol Biol Rep 49, 4633–4641 (2022). https://doi.org/10.1007/s11033-022-07311-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11033-022-07311-6

Keywords

Search

Navigation