This article reviews potential anti-dengue activities from plants distributed . In the Philippines, Euphorbia hirta, known locally as “tawa–tawa”. Management of thrombocytopenia and flu-like symptoms in dengue patients with herbal water of Euphorbia hirta. Mir M, Khurshid R, Aftab R. BACKGROUND. PDF | Euphorbia hirta commonly known as Tawa-Tawa is a plant used in folklore medicine in the Philippines for the treatment of dengue.

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Dengue fever causes mortality and morbidity around the world, specifically in the Tropics and subtropic regions, which has been of major concern to governments and the World Health Organization WHO. As a consequence, the search for new anti-dengue agents from medicinal plants has assumed more urgency than in the past. Medicinal plants have been used widely to treat a variety of vector ailments such as malaria.

The demand for plant-based medicines is growing as they are generally considered to be safer, non-toxic and less harmful than synthetic drugs. This article reviews potential anti-dengue activities from plants distributed around the world.

Sixty-nine studies from to describe 31 different species from 24 families that are known for their anti-dengue activities. About ten phytochemicals have been isolated from 11 species, among which are compounds with the potential for development of dengue treatment. Crude extracts and essential oils obtained from 31 species showed a broad activity against Flavivirus.

Potential Use of Euphorbia hirta for Dengue: A Systematic Review of Scientific Evidence

Current studies show that natural products represent a rich potential source of new anti-dengue compounds. Further ethnobotanical surveys and laboratory investigations are needed established the potential of identified species in contributing to dengue control. Dengue fever is caused by the arthropode-borne flavivirus named dengue virus DENVtransmitted by the Aedes aegypti mosquito [ 1 ].

To date, four antigenically related but distinct virus serotypes DENV-1, 2, 3 and 4 have been identified as belonging to the genus Flavivirus in the Flaviviridae family [ 2 — 4 ]. Infection with one DENV serotype produces only specific antibody against that serotype. When antibody from the first infection is neutralized, secondary infections by other serotypes can cause more serious infection [ 5 ].

In recent years, the current dengue epidemic has become a focus of international public health awareness. Unlike malaria, which is more prevalent in remote areas, cases of dengue are distributed mostly in urban and sub-urban areas [ 89 ]. This has made the epidemic more lethal as an outbreak is difficult to control due to highly populated areas in cities. Recovery from first type of infection provides lifelong immunity; however, it affords only half protection from subsequent viral infection that ultimately results in the risk of DHF.

Euphorbia hirta – a possible cure for dengue

Most dengue infections are characterized by non-specific symptoms including frontal headache, retro-orbital pain, body aches, nausea and vomiting, joint pains, weakness and rash [ 1213 ]. International travel, increasing human population [ 1415 ] and urbanisation create suitable conditions for the mosquito vector Ae.

The first case of DHF was discovered in the s in Thailand and the Philippines [ 4 ], where the first two DENV serotypes were identified, followed by the third and fourth serotypes in [ 14 ]. Since then, DHF has recorded major cases resulting in hospitalization and death among children in regions stretching from Asia to Africa and the Pacific [ 4 ].

Despite its lethal consequences, the staggering numbers of those affected are increased by the fact that, at present, there is no specific antiviral treatment or vaccine for DF [ 3 ]. Early diagnosis and strict hospitalization often save the life of patients with DHF [ 3410 ]. Efforts to combat the vector have been undertaken by regulatory bodies in an attempt to tackle this problem by awareness campaigns and vector control [ 16 ].

Others strategies include the use of plants with bioactive substances that have toxic properties to the vector or insecticidal properties [ 20 ]. Clearly, development of antiviral drugs and vaccines is needed in order to support these programs. Moreover, a safe, low-cost, and effective vaccine to control DENV woudl be needed, especially in the most affected countries, which are poor [ 216 ].

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Potential anti-dengue medicinal plants: a review

Therefore, the search of highly selective but non-toxic antiviral compounds is urgently needed in view of the spread of dengue disease throughout the world [ 23 ]. Green Countries or areas at risk of dengue, The contour lines of the January and July isotherms indicate denguf potential geographical limits of the northern and southern hemispheres for year-round survival of Aedes aegyptithe principal mosquito vector of dengue viruses.

Guangdong province in China has become a major uirta with reported cases of dengue [ 24 ]. From toa total of 2, cases of dengue were recorded. The epidemic peaked in In Northern Thailand there were 13, 11, 6, 6, and 6, DF cases reported during the period — [ 25 ].

In Malaysia, with a population of The first case was documented in [ 162829 ]. During the period —, 12, dengue cases hirat reported, with a fatality rate of 3. The number of cases euphrobia in following decade of — with 26, cases; however, the fatality rate was down to 0. In denugedengue was reported with 13, and 15, incidence rate, respectively, perpopulation. With an increase of In the period —, the number of dengue cases decreased to 21, cases with the peak appearing in Fig. Reported dengue cases in the years — in Malaysia [ 32 — 36 ].

Since early human civilization, plants have been a source of traditional medicine, and demands for herbal and natural product have recently increased.

Several studies have reported potential antiviral agents from plants in the form of crude extracts, denge oils or purified compounds [ 4142 ]. Recent studies have reported the potential of some flavonoid compounds as antivirals against DENV-2 [ 4043 ]. Dengue infection is caused by bites of the female Ae.

During this period, the virus may get into the peripheral bloodstream and, if left untreated, can damage blood vessels and lymph nodes resulting in DHF with symptoms such as bleeding from the nose, gums or under the skin [ 18 ]. DSS can result in death if proper treatment is not provided. Aedes mosquitoes are small and black with white markings on the body and legs. Female mosquitoes need blood from biting humans or animals to produce live eggs.

The principal vector of dengue Ae. Mosquito bites are the only route of DENV spread. The transmission of DENV is often from human to human through domestic mosquitoes [ 6 ]. After being transmitted to a new human host by infected mosquitoes, the virus replicates in euphodbia lymph nodes and spreads through the lymph and blood to other tissues [ 6 ]. To identify a potential antiviral treatment for DENV, it is necessary to understand the life cycle of the virus.

The dengue virion is a small particle with a lipoprotein envelope and an icosahedral nucleocapsid containing a positive single-stranded RNA genome [ 61223 ]. Virus infection of the cell begins with binding euphlrbia the host cell surface. It enters the cell by receptor-mediated endocytosis [ 15 ], with the cell membrane forming a sac-like structure known as an endosome. In the endosome, the virus penetrates deep into the cell until the endosome membrane acquires a negative charge, which allows it to fuse with the endosomal membrane to open a port for release of genetic material.

At this point, the virus in the cell fluid starts to reproduce. Changes in the acidity of the secretory pathway during this viral journey travel play an important role in its maturation Fig. There are currently no specific treatments for dengue fever [ 22 ]. Only standard treatment for management of fever is given, i. Patients with dengue fever will be treated symptomatically, for example, sponging, acetaminophen [ 9 ], bed rest and oral rehydration therapy, and if signs of dehydration or bleeding occur the patients are usually hospitalized [ 6 ].

Aspirin should be avoided because it may cause bleeding [ 9 ]. Current prevention of dengue by potential dengue vaccine and vector control is highly cost effective [ 2245 ]. In addition, mosquito control programs are the most important preventive method [ 6 ]. However, these are difficult to implement and maintain [ 39 ]. Development of a vaccine for dengue is difficult since there are four closely related, but antigenically distinct, serotypes of the virus that can cause disease [ 646 ].

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Infection by one serotype does not ensure protection of the patient from infection by the other three serotypes [ 15 ]. Therefore, if vaccine were produced for only one or two serotypes, the other serotypes would increase the risk of more serious illness [ 47 ].

Ribavirin has shown significant in vivo activity against RNA viruses; however, it exhibited only very weak activity against Flaviviruses [ 21 ]. A possible strategy in the treatment of dengue is to use chimeric tetravalent vaccines that show high euphrbia antibody against all dengue serotypes [ 915 ].

Studies on the development of tetravalent vaccines are ongoing in Thailand and these should be available in the near future euphorbiaa 6 ]. In addition, recombinant vaccines against capsid, premembrane and hkrta genes of DENV-1, -2 and -3 inserted into a copy eupuorbia a DNA infectious clone of DENV-2 are being developed and are currently undergoing clinical trials [ 48 ].

Natural products have become the main source of test material in the development of antiviral drugs based on traditional medical practices [ 50 ].

Traditional medicines are based on knowledge, experience and practices based on indigenous cultural beliefs and knowledge, and are used to maintain health, prevent, treat and diagnose physical or mental illness [ 49 ]. Traditional medicinal plants have been reported to have antiviral activity [ 495152 ] and some have been used to treat viral infections in animals and humans.

Practitioners of traditional medicines believe that decoction of tawa—tawa leaves can reverse viral infection and prevent the fever from moving into critical stages, although there are no scientific studies proving its effectiveness [ 54 ]. Sometimes, tawa—tawa is prepared together with papaya leaves since papaya leaf extract has a function as an antibiotic to cure fever.

While papaya leaf extract kills the bacterial infection that caused the fever, tawa—tawa extract prevents bleeding. In addition, unpublished research has found that Psidium guava leaves are a good way to increase platelets, thus helping to avoid bleeding [ 55 ].

A water decoction of guava leaves contains quercetin, which acts to inhibit the formation of enzyme mRNA in the virus [ 56 ].

The use of herbal-based medicine and medicinal plants to treat many diseases is growing worldwide as they has few or no adverse effects. In addition, we describe species used as traditional treatment for dengue together with their isolated compound.

Alternanthera philoxeroides belongs to family Amaranthaceae.

It originated from South America but is currently euphorbiq Australia. The effect of A. An MTT assay was carried out to determine the cytotoxicity of A. Coumarin extract of A. Andrographis paniculata belongs to jirta Acanthaceae. The methanolic extract of A. Azidarachta indica belongs to the family Meliaceae.

It is native to India and Pakistan and grows throughout tropical and semi-tropical regions. The in vitro and in vivo inhibitory potential of aqueous extract of Azidarachta indica neem leaves on the replication of DENV-2 was evaluated [ 8 ].

Cytotoxicity studies were carried out to determine the MNTD in a virus inhibition assay. The aqueous extract of neem leaves NL completely inhibited —10, tissue culture infective dose TCID 50 of virus as indicated by the absence of cytopathic effects at its maximum non-toxic concentration of 1.

An in vivo study on the inhibitory effects on virus of NL aqueous extract in day-old suckling mice was carried out by intracerebral inoculation.