Immunomodulatory Activities of Carica papaya L. Leaf Juice in a Non-Lethal, Symptomatic Dengue Mouse Model.

Mohd Ridzuan Mohd Abd Razak,Adlin Afzan,Ravindran Thayan,Murizal Zainol,Ami Fazlin Syed Mohamed,Nur Hana Md Jelas,Adiratna Mat Ripen,Nor Azrina Norahmad,Norazlan Mohmad Misnan

doi:10.3390/pathogens10050501

Mohd Ridzuan Mohd Abd Razak, Adlin Afzan + Show 7 more

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https://doi.org/10.3390/pathogens10050501

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Abstract

The role of Carica papaya L. leaf juice in immune dysregulation caused by dengue virus infection remains unclear. This study aimed to investigate the immunomodulatory activities of the freeze-dried C. papaya leaf juice (FCPLJ) on AG129 mice infected with a clinical DENV-2 (DMOF015) isolate. The infected AG129 mice were orally treated with 500 and 1000 mg/kg/day of FCPLJ, for three days. Platelet, leukocyte, lymphocyte and neutrophil counts were microscopically determined. The level of plasma proinflammatory cytokines was measured by multiplex immunoassay. The levels of intracellular cytokines and viral RNA were determined by RT-qPCR technique. The results showed that the FCPLJ treatment increased the total white blood cell and neutrophil counts in the infected mice. The FCPLJ treatment decreased the level of GM-CSF, GRO-alpha, IL-1 beta, IL-6, MCP-1 and MIP-1 beta in the plasma of the infected mice. The intracellular IL-6 and viral RNA levels in the liver of infected mice were decreased by the FCPLJ treatment. In conclusion, this study supports the potential immunomodulatory role of the FCPLJ in a non-lethal, symptomatic dengue mouse model. Further studies on the action mechanism of the C. papaya leaf juice and its possible use as adjunctive dengue immunotherapy are warranted.

Highlights

It was estimated that 390 million dengue cases will occur each year, and 3.9 billion people in 128 countries are at risk of dengue virus infection [1]
The dengue virus tropism in AG129 mice correlates with human dengue autopsy studies [28]
As compared to our previous dengue mouse model, which was established by a lab strain dengue virus infection [26], the current symptomatic dengue mouse model showed higher production of proinflammatory plasma cytokines

Summary

Introduction

Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Dengue is a mosquito-borne disease, which is still endemic in more than 100 countries, including the Americas, South-East Asia and Western Pacific regions. It was estimated that 390 million dengue cases will occur each year, and 3.9 billion people in 128 countries are at risk of dengue virus infection [1]. The disease can cause a severe flu-like illness

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