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Archives of Virology

, Volume 164, Issue 4, pp 1095–1110 | Cite as

Evaluation of anti-dengue activity of Carica papaya aqueous leaf extract and its role in platelet augmentation

  • Navita Sharma
  • Kamla Prasad MishraEmail author
  • Sudipta Chanda
  • Varun Bhardwaj
  • Himanshi Tanwar
  • Lilly Ganju
  • Bhuvnesh Kumar
  • Shashi Bala Singh
Original Article
  • 64 Downloads

Abstract

Dengue disease is characterized by a marked decrease in platelet count, which is life threatening. In the present study, we investigated the antiviral activity of an aqueous extract of Carica papaya leaves (PLE) against dengue virus (DENV) and its effect on platelet augmentation. The anti-dengue activity of PLE in DENV-infected THP-1 cells was examined by immunoblotting and flow cytometry. The effect of PLE on erythrocyte damage was investigated using hemolytic and anti-hemolytic assays. Virus-infected THP-1 cells were assayed for IFN-α secretion. The effect of PLE on platelet augmentation in rats with cyclophosphamide-induced thrombocytopenia was also investigated. The platelet count of blood from the retro-orbital plexus of rats was determined on the 1st, 4th, 7th, 11th and 14th day of study. On the 14th day, the rats were sacrificed for histopathological examination of the liver, kidney and spleen. Plasma of thrombocytopenic rats was tested for thrombopoietin (TPO) and IL-6 secretion. The data suggest that PLE significantly decreases the expression of the envelope and NS1 proteins in DENV-infected THP-1 cells. A marked decrease in intracellular viral load upon PLE treatment confirmed its antiviral activity. This also resulted in a significant decrease in erythrocyte damage and hydrogen-peroxide-induced lipid peroxidation. A significant increase in the number of platelets was found in thrombocytopenic rats treated with PLE, along with an increase in IL-6 and TPO levels. These findings suggest that PLE can potentially be used as an antiviral agent, as it helps in platelet augmentation and exhibits antiviral activity against DENV.

Abbreviations

DENV

Dengue virus

PLE

Papaya leaf extract

DHF

Dengue hemorrhagic fever

DSS

Dengue shock syndrome

WHO

World Health Organization

FBS

Fetal bovine serum

UPLC

Ultra performance liquid chromatography

LC-MS

Liquid chromatography mass spectrometry

hPBMCs

Human peripheral blood mononuclear cells

IFN-α

Interferon alpha

MTT

3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyltetrazoliumbromide

HE

Hematoxylin and eosin

TPO

Thrombopoietin

Notes

Acknowledgements

The authors thank the Defence Research & Development Organization (DRDO), Government of India, for financial support. NS thanks the Council of Scientific and Industrial Research for providing a fellowship in the form of a Junior and Senior Research Fellowship. She also thanks Dr. Sachin Kolte (Associate Professor, MD Pathology, Safdarjung Hospital, Delhi, India) in helping in analyzing histopathological slides of different organs of rats.

Funding

This study was funded by the Defence Research & Development Organization (DRDO) [DIP-264]. NS thanks the Council of Scientific and Industrial Research CSIR for providing a fellowship in the form of a Junior and Senior Research Fellowship.

Compliance with ethical standards

Conflict of interest

All authors declare that they have no conflict of interest.

Ethical approval

This article does not contain any studies with human participants performed by any of the authors. All animal protocols were approved by the DIPAS Institutional Animal Ethics Committee (IAEC/DIPAS/2015-25, 18/10/2015).

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Copyright information

© Springer-Verlag GmbH Austria, part of Springer Nature 2019

Authors and Affiliations

  • Navita Sharma
    • 1
  • Kamla Prasad Mishra
    • 1
    • 2
    Email author
  • Sudipta Chanda
    • 1
  • Varun Bhardwaj
    • 1
  • Himanshi Tanwar
    • 1
  • Lilly Ganju
    • 1
  • Bhuvnesh Kumar
    • 1
  • Shashi Bala Singh
    • 1
  1. 1.Defence Institute of Physiology and Allied Sciences (DIPAS), DRDONew DelhiIndia
  2. 2.O/o Director General (Life Sciences)Defence Research and Development OrganizationNew DelhiIndia

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