Dengue Fever: Therapeutic Potential of Carica papaya L. Leaves

Md Moklesur Rahman Sarker, Farzana Khan, Isa Naina Mohamed, Md Moklesur Rahman Sarker, Farzana Khan, Isa Naina Mohamed

Abstract

Dengue, a very widespread mosquito-borne infectious disease caused by Aedes aegypti virus, has been occurring during the monsoons every year. The prevalence and incidence of dengue fever and death due to its complications have been increased drastically in these recent years in Bangladesh, Philippines, Thailand, Brazil, and India. Recently, dengue had spread in an epidemic form in Bangladesh, Thailand, and Philippines. Although the infection affected a large number of people around the world, there is no established specific and effective treatment by synthetic medicines. In this subcontinent, Malaysia could effectively control its incidences and death of patients using alternative medication treatment mainly prepared from Carica papaya L. leaves along with proper care and hospitalization. Papaya leaves, their juice or extract, as well as their different forms of preparation have long been used traditionally for treating dengue fever and its complications to save patients' lives. Although it is recommended by traditional healers, and the general public use Papaya leaves juice or their other preparations in dengue fever, this treatment option is strictly denied by the physicians offering treatment in hospitals in Bangladesh as they do not believe in the effectiveness of papaya leaves, thus suggesting to patients that they should not use them. In Bangladesh, 1,01,354 dengue patients have been hospitalized, with 179 deaths in the year 2019 according to information from the Institute of Epidemiology, Disease Control, and Research as well as the Directorate General of Health Services of Bangladesh. Most of the patients died because of the falling down of platelets to dangerous levels and hemorrhage or serious bleeding. Therefore, this paper aims to critically review the scientific basis and effectiveness of Carica papaya L. leaves in treating dengue fever based on preclinical and clinical reports. Thrombocytopenia is one of the major conditions that is typical in cases of dengue infection. Besides, the infection and impairment of immunity are concerned with dengue patients. This review summarizes all the scientific reports on Carica papaya L. for its ability on three aspects of dengue: antiviral activities, prevention of thrombocytopenia and improvement of immunity during dengue fever.

Keywords: Aedes aegypti virus; Carica papaya; dengue; dengue treatment; immunity; thrombocytopenia; tropical disease; viral infection.

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Copyright © 2021 Sarker, Khan and Mohamed.

Figures

FIGURE 1
FIGURE 1
Outline of the Study: Therapeutic Potential of Carica papaya L. Leaves against dengue fever.
FIGURE 2
FIGURE 2
Mechanism of inhibition of the formation of platelets in bone marrow by dengue virus. The panel illustrates the steps in the formation of platelets from the liver that is stimulated by low platelet count in the blood. After the infection of the host with dengue virus, it prevents the formation of platelets from stromal cells and maturation in different stages.
FIGURE 3
FIGURE 3
Mechanism of platelet destruction by antibody cross-reaction induced by dengue virus. Invading viral proteins mimics the platelets of the body and are destroyed by IgM antibodies produced upon recognition of viral proteins by the host defense system.
FIGURE 4
FIGURE 4
Mechanism of platelets and other cells’ aggregation in thrombocytopenia induced by dengue virus. After dengue infection, platelets are aggregated with endothelial cells that in turn activate the platelets. P-selection proteins on platelet cells are recognized by neutrophils and monocytes and form further aggregation. Leukocytes also interact with the platelet endothelial cell aggregates. These aggregations reduce the available platelet count and induce an inflammatory response that destroys the platelets.
FIGURE 5
FIGURE 5
Summary of processes behind thrombocytopenia in dengue. The panel summarizes how platelets are destroyed after dengue infection. After viral replication in platelets, it activates platelets using receptors and monocytes as well as aggregates the platelets, reducing its availability. It also suppresses bone marrow and prevents platelet formation by destroying premature cells.
FIGURE 6
FIGURE 6
Phytocompounds isolated from Carica papaya L. leaves.
FIGURE 7
FIGURE 7
Possible mechanisms behind the role of papaya leaves in improving platelet count. This figure summarizes the mechanism of papaya leaves in reducing thrombocytopenia by the dengue virus. It stabilizes the membrane of platelets and reduces platelet destruction. It also prevents viral assembly in cells and hemolysis. Furthermore, it increases the expression of genes that elevate the production of platelets.
FIGURE 8
FIGURE 8
Mechanisms behind the role of papaya leaves in improving platelet count by membrane stabilization and production of ALOX 12 gene. Carica papaya L. leaf extract promotes the formation of megakaryocytes and megakaryocyte progenitors that induce the formation of proplatelets. Lysis and destruction of these proplatelets are also inhibited by Carica papaya L. leave extract.

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