USE OF EUPHORBIA HIRTA (TAWA-TAWA) IN THE MANAGEMENT OF DENGUE PATIENTS
USE OF EUPHORBIA HIRTA (TAWA-TAWA) IN THE MANAGEMENT OF DENGUE PATIENTS

SUMMARY OF EFFICACY AND SAFETY/TOLERABILITY DATA


Review of related literature revealed that there is no sufficient evidence to support the efficacy and safety of Euphorbia hirta (tawa-tawa) in the management of patients with dengue fever or dengue hemorrhagic fever

INTRODUCTION

Euphorbia hirta, more commonly known as tawa-tawa, gatas-gatas, or botobotonis in the Philippines, is a small, erect or ascending, slender-stemmed, annual herb, spreading up to 45 cm tall, though sometimes can be seen lying down. The plant has a hairy stem with many branches from the base to the top. The stem and leaves of E. hirta produce a white or milky juice when cut. This plant commonly grows in tropical countries, especially in roadsides and on wasteland. It is widely abundant in the Philippines.1,2,3 E. hirta is also known as E. pulifera, E. capitata, Chamaesyce hirta, snakeweed, pill-bearing spurge, hairy spurge, asthma weed, and asthma plant.4,5

Whole plant or leaf extracts of Euphorbia hirta is known to have a multitude of actions in the biological system.6

In Asia and Australia, the herb is widely used in traditional medicine to treat a variety of medical conditions including asthma, coughs, diarrhea, and dysentery. In east, central, and west Africa, a decoction of the herb is used to treat asthma, oral thrush, boils, sores, and skin and wound infections, in addition to its use as an antispasmodic, antipruritic, carminative, depurative, diuretic, febrifuge, galactagogue, purgative and vermifuge.3 In Mauritius, a decoction of the plant is used to treat respiratory tract infections, vomiting, fever, bronchitis, and pulmonary disorders. In Nigeria, exudates of the stem is used to treat eye and ear infections, while a decoction of the plant is used to treat enteric infections including diarrhea and dysentery, constipation and other stomach problems, asthma, bronchitis, eczema, athletes foot and scorpion bite pains.3

It is usually taken in dosages of 0.1 to 0.3 g of dried powdered herb 3 times daily or 0.12 to 2 mL of liquid extract 3 times daily, and repeated over 2 to 3 weeks.3 E. hirta is registered in Mali as a remedy against diarrhea and dysentery. The powder of aerial parts is used for the production of medicinal preparation marketed under the name Dysenteral®. This product is included in the National List of Essential Drugs in Mali.7,8

In animal studies, E. hirta had been reported to exhibit antibacterial, antiamoebic, antifungal, antiviral, spasmolytic, antidiarrheal, sedative, anxiolytic, analgesic, antipyretic, anti-inflammatory, antimalarial, and antihypertensive properties.9 E. hirta was reported to contain coumarins, flavonoids, tannins, sugars, mucilage, reduced compounds, sterols and triterpenes including phytosterols, cardiac glycosides, diterpenes (phorbol esters), aromatic acids (shikimic and related acids), alkaloids, and anthocyanins.7 A number of compounds have been isolated from E. hirta and were chemically characterized. These include cycloarternol, 24-methylene-cycloarternol, β-sitosterol, euphorbol, hexacozonate, α-amyrin, β-amyrin, 1-hexacosanol, ingeno-triacetate, tinyaloxin, p-coumaric acid, campesterol, stigmasterol, and quercitin.7,10

However, despite the array of chemical compounds characterized from E. hirta, and the diverse local medicinal uses of the plant, very little clinical pharmacological evaluations have been carried out to ascertain the rationale behind most of the folkloric claims of its efficacy.

More recently, concerns from local authorities have been raised in the reported rampant indiscriminate use of E. hirta in the management of dengue patients. Despite, warnings from health authorities that there is not enough efficacy and safety data to support its clinical use, patients and health professional continued to use E. hirta. The confidence of the general public in the effectiveness of E. hirta in treating dengue cases was solely based on the results of animal studies showing that it exerts a platelet count-increasing activity, and testimonials from patients or health professionals who claimed to experience clinical benefits from its use.

To safeguard the public, more detailed information should be provided to let both the patients and the health professionals fully understand the potential dangers of using E. hirta in dengue patients or in any other medical conditions.

Clinical studies

An exhaustive search for literature was conducted, but no published local or international reports of clinical trials conducted on E. hirta use in the treatment of dengue fever or dengue hemorrhagic fever were found.

An observational clinical study was conducted in Davao Medical Center in 2003 to test the efficacy of E. hirta decoction on male and female pediatric patients (aged 2 to 10 years) with acute dengue fever (n=137). The patients were assigned to open-labeled treatment with either E. hirta decoction plus standard therapy or with standard therapy alone. No details can be provided on the number of patients assigned to each treatment group. The dosing regimen of E. hirta decoction was not standardized. Both the preparation and the administration of the E. hirta decoction were done by the guardians of the patients. The amount administered to each patient was uncontrolled (also under the discretion of the guardian). The patients were treated for 3 to 5 days, depending on the length of hospital stay. Results of this study showed that patients who received the E. hirta decoction in addition to standard therapy experienced significantly greater increases in platelet counts compared to the patients who received standard therapy alone. No treatment-emergent adverse events were reported in both treatment groups.11

All the information presented in this summary was obtained through a personal interview with the investigator. The results of this observational study was not published but, according to the investigator, a formal report was submitted to the Philippine Pediatric Society during their annual convention in April 2004.11

Animal studies

In a study conducted in the University of Santo Tomas, E. hirta was found to exert significant platelet-increasing activity. The effect of E. hirta, prepared either as a decoction or an ethanolic extract, on platelet, RBC, and WBC counts was investigated using Sprague-Dawley rats (6 to 8 weeks old) as test animals. The test animals were divided into two major groups: decoction and ethanolic extract groups. Each group was further subdivided into two subgroups (consisted of 2 male and 4 female Sprague-Dawley rats) which were assigned to receive either 60.4 mg/kg or 483.0 mg/kg of the decoction or the ethanolic extract. The two doses used in this study were the lowest and highest doses tested for hematologic toxicity in a study conducted in Nigeria.12,13

Results of the study showed that both the decoction and the ethanolic extract of E. hirta, at doses of 60.4 mg/kg and 483.0 mg/kg have a significant effect on the platelet counts of Sprague-Dawley rats. The RBC and WBC counts were not significantly affected, demonstrating that E. hirta does not affect the circulating RBC or the erythropoietic centers of the experimental animals, and it does not induce production or destruction of the WBC. The mean increases in platelet count in the decoction and ethanolic extract groups did not significantly differ, suggesting that both preparations can be used for further studies. The difference in the mean platelet counts of subgroups who received the 60.4 mg/kg and 483.0 mg/kg doses was not significant as shown in Dunnet’s test. This finding indicated that the platelet-increasing activity of E. hirta was not dose-dependent.12

The platelet-increasing activity of E. hirta was further evaluated by determining the effect of the plant material on stimulating platelet production in the bone marrow. In this evaluation, the dose and preparation (483.0 mg/kg of the ethanolic extract) that produced the greatest numerical increase in platelet count during the initial evaluation was used. Anagrelide, a drug which inhibits the maturation of megakaryocytes into platelets, was administered to decrease the platelet counts of the test animals. After exposure to anagrelide, 483.0 mg/kg of ethanolic extract was administered to 50% of the test population. Results of this further evaluation showed that the mean platelet count did not differ significantly in the group which received both anagrelide (125 µg/day) and ethanolic extract of E. hirta (483.0 mg/kg) and in the group who were only exposed to anagrelide (control). This suggested that the platelet-increasing activity of E. hirta was not due to stimulation of the platelet production in the bone marrow.12

The investigators concluded that the increase in platelet count observed after administration of E. hirta was possibly caused by the prevention of altered distribution of platelets or prevention of platelet destruction.12


In another study conducted by the students of St. Mary’s School in Davao, E. hirta was also found to increase the platelet counts of white mice (Mus musculus). E. hirta was prepared in a teabag form. The results of this study were not published, and therefore, no further information was obtained.14

In Nigeria, the effects of aqueous and methanolic extracts of E. hirta on platelet count, bleeding time, and clotting time were also investigated. The extracts of E. hirta were administered orally to albino Wistar rats. Platelet count, bleeding time, and clotting time were determined before, and at different time intervals after administration of the extracts. At 60 minutes, the aqueous extract reduced bleeding time by 54% compared to 49.5% for methanolic extract, and the difference was significant (p