Received date: April 18, 2013; Accepted date: June 03, 2013; Published date: June 05, 2013
Citation: Bharadwaj S, Shraddha N, Joshi VK (2013) An Open Comparative Randomized Clinical Study of Plant Based Drugs Embelia Robusta Roxb and Mallotus Philippinensis Muell on Intestinal Parasites. J Gastroint Dig Syst 3:122. doi: 10.4172/2161-069X.1000122
Copyright: © 2013 Bharadwaj S, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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Background: Intestinal parasites are common cause of morbidity. Aim: To compare the efficacy and safety of two plant based drugs Embelia robusta Roxb and Mallotus philippinensis Muell on intestinal parasites. Methods: Forty Patients exhibiting symptoms of parasitic infection were diagnosed and confirmed by stool test. They were then randomized to either Embelia in a dose of 5 g or Mallotus in dose of 1 g with honey and jaggery as adjuvant respectively. Drugs were administered for a period of one week and follow-up was carried in 15 days and thereafter a month to observe symptomatic relief and presence or absence of ova/cyst in stool sample examination. Results: Symptomatic relief was found in Mallotus while some symptoms still persisted with Embelia. Embelia robusta had 40% cure rate while Mallotus had 70% cure rate, but both the drugs did not result in any adverse effects. Conclusions: It was observed that Mallotus philippinensis had better efficacy.
Embelia robusta Roxb; Mallotus Philippinensis uell; Intestinal parasites; Comparative study
The prevalence of human diseases is increasing rapidly worldwide, as is the number of deaths from diseases . Intestinal parasites are one of the most common infections in humans. It is estimated that 60% of the world’s population is infected with gut parasites, which play role in morbidity [2,3]. 3.5 billion people are affected, 450 million are ill as a result of these infections, the majority being children. 44 million pregnant women have hookworm infections which cause chronic blood loss from the intestine and predisposes to the development of iron deficiency anaemia. 65,000 deaths are directly attributable to hookworm infections 60,000 to Ascaris . These cause morbidity in human in different ways, by affecting nutritional equilibrium, including intestinal bleeding, inducing malabsorption of nutrients, competing for absorption of micronutrients, reducing growth, reducing food intake, causing surgical complications such as obstruction, rectal prolapse and abscess, affect cognitive development [5,6].
Inspite of great measures in the control of parasites, it still continues to be a major health problem which has compelled to think over less toxic and more effective alternative source i.e. from plant source.
Embelia robusta burm. is one such plant claimed to be best in the treatment of pathogens as documented in Indian traditional system of Medicine  It is advocated to be used with honey as an adjuvant . Also glands and hairs covering the fruit of Mallotus philippinensis muell have also been mentioned for the treatment of pathogens . The adjuvant advised here is jiggery .
The study aims to compare the efficacy of these two drugs on selected parasites.
The study was open labeled, comparative, interventional randomized trial.
Preparation of the drug
Plant material: Market Samples of Embelia robusta and Mallotus philippinensis Muell were collected from different crude drug markets and subjected to High Performance liquid chromatography (HPLC), this being one of the widely used methods for separation and quantitative estimation of phenolic acid content present in them. The samples having highest cinnamic acid content was chosen for the study. Cinnamic acid is a phenolic acid with anthelmintic, anti-viral, antioxidant and antifungal property [11-14]. As per the references in the classics Embelia robusta Roxb was advised with honey  and Mallotus philippinensis Muell tablets was prepared by admixture of glands and hairs of Mallotus and jaggery in twice the proportion .
Administration of drug
Embelia robusta Roxb fruit powder in the dose of 5 g orally was advised to be taken with honey, glands and hairs of Mallotus philippinensis Muell was made into tablets and administered in the dose of 500 mg orally for children and 1g to the adults. This dose was arrived at after referring the Ayurvedic classics and Ayurvedic Pharmacopoea of India .
Methodology for clinical trial
Type of study- Interventional study
Study design - open randomized controlled clinical trial
Patient selection- Allocation randomized open labelled clinical controlled trial.
End point classification- Clinical efficacy
Intervention model- Parallel assignment
Phase of trial- phase III trial
Locale of study
The study subjects were selected from the outpatient department, S.S. Hospital, Banaras Hindu University, Varanasi.
Screening and recruitment of the patients
Twenty patients of different age groups who exhibited symptoms of parasitic infection were selected for each test drug and their stools were examined microscopically in the Department of Microbiology, Institute of Medical Sciences, Banaras Hindu University, Varanasi to confirm the presence of ova/cyst of helminthes. Before the commencement of the trial Institutional Ethics committee approval was obtained .Written informed consent and assent was obtained prior to enrollment of the patients. Also it was conducted in accordance to ICMR ethical guidelines for biomedical research on Human Participants, 2006.
A total number of forty patients were enrolled in this trial.
Grouping of the patients
Group A: Twenty patients presenting with symptoms and signs of infestation were treated with powder of Embelia with Honey.
Group B: Twenty patients exhibiting the signs and symptoms of infestation received Mallotus with jaggery.
Procedure Of clinical trial
Forty patients were selected from O.P.D. of S.S. Hospital, I.M.S; B.H.U. Twenty patients were treated with Embelia and twenty with Mallotus. Their age varied from 3-45 years. Patients of both sexes were selected. The diagnosis was based on their symptoms and signs and confirmed by examining their stools microscopically for the presence of ova/cyst. Follow-up of patient was done at the end of 7 days, 15 days and one-month duration of the treatment. Each week their stool was examined in the lab for the presence of ova/cyst and results were noted.
Diets and habits
The patients were advised to avoid sweet substances and to maintain personal hygiene particularly to wash hands before food and after defecation.
Diagnosis of the patients
Clinical diagnosis has been done on the basis of signs and symptoms exhibited by the patients.
Laboratory diagnosis - ova/cysts and parasite examination of the stool was done which included direct wet mount. A drop of saline was placed on left half of the slide and one drop of iodine on the right half. With a wooden stick, a small portion of stool was introduced into the drop of saline and iodine. A cover slip was placed on this and examined under the microscope in systemic manner. Low power examination (x100) of entire 22 by 22 mm cover slip preparation (both saline and iodine); high dry power examination (x400) of at least one third of the cover slip area (both saline and iodine) was done. In low power, larvae, ova, segments, RBCs and WBCs can be seen while in high power trophozoites, cysts etc can be screened.
Parameters for efficacy assessment
The results were assessed on the basis of repeated negative stool report for three consecutive days and relief in symptoms and signs were classified as follows:
Cured - Those cases who had symptomatic relief with negative stool report after the treatment.
Improved - Cases showing symptomatic relief but positive stool reports for ova.
Unchanged - Cases whose stool reports were negative for ova and only partial or no symptomatic relief was noted.
The results of the study are presented under the following headings:
Results of Study Drugs
Demographic profile presents distributions of patients suffering from infestation according to age, sex, domicile status, socio-economic status, religion, personal hygiene, occupation, dietary habit and residential sanitation.
Clinical profile comprises of incidence of general signs and symptoms, also characteristic symptoms.
Treatment and response include comparison of baseline characteristics, concomitant medication and follow up in different study groups.
Most of the patients i.e. out of 40, 15 (37.5%) belonged to 11-20 years of age group followed by 1-10 yrs (35%), 21-30 yrs (15%) and 31-40 yrs (12.5%) (Table 1). Also 67.5 percent patients were male whereas female were 32.5percent (Table 2). The incidence of worm infestation is more in rural areas than in urban. A maximum of 30 patients constituting 75 percent of the study sample were rural people, whereas 25 percent belonged to urban area (Table 3). The incidence of worm infestation was seen highest in patients with poor hygiene (55%) (Table 4).
|Distribution of patients (%) according to age (n = 40)|
|Age Group (in years)||No. of patients||Percentage (%)|
|1 - 10||14||35.0|
|11 - 20||15||37.5|
|21 - 30||6||15.0|
|31 - 40||5||12.5|
Table 1: Incidence of Age.
|Distribution of patients (%) according to sex (n = 40)|
|Sex||No. of patients||Percentage (%)|
Table 2: Incidence of Sex.
|Distribution of patients (%)on the basis of domicile status (n = 40)|
|Domicile Status||No. of cases||Percentage (%)|
Table 3: Incidence according to Domicile Status.
|Distribution of patients (%) according to personal hygiene (n = 40)|
|Personal Hygiene||No. of cases||Percentage (%)|
Table 4: Incidence of Personal Hygiene.
It was been observed that this condition is more common in students (72.5%) followed by housewives (12.5%), farmer (7.5%), businessmen (5%) and 2.5% were from service class (Table 5). Vegetarian and nonvegetarian diet has nearly the same significance as worm infestation can be equally transmitted through improperly washed vegetables, improperly cooked vegetarian as well as non-vegetarian diet, as they carry ova/cyst forms (Table 6).
|Distribution of patients (%) according to occupation (n = 40)|
|Occupation||No. of cases||Percentage (%)|
Table 5: Incidence of occupation.
|Distribution of patients (%) according to dietary habits (n = 40)|
|Dietary Habits||No. of cases||Percentage (%)|
Table 6: Incidence of dietary habits.
Among forty patients examined for the presence of ova/cyst by stool examination, sixteen were positive for ova of Ascaris, followed by cyst of Entamoeba histolytica in seven patients, cyst of Giardia lamblia in 5 patients and ova of Hymenolepis nana in four patients. Mixed infestation was seen in four patents. Ancyclostoma and Taenia was observed in only two patients (Table 7).
|Number of patients in whose stool samples different ova/cysts were detected (n = 40)|
|S.N.||Ova / Cyst||No of cases|
|7.|| Mixed infestation
Ascaris + Giardia
Ascaris + trichuris
Cyclospora + Idamoeba
Ascaris + Taenia + trichuris
Table 7: Incidence of ova/cysts.
Results of study drugs
Table 8 shows comparison of demographic variables in different study groups. There is no statistically significant difference among both groups with respect to age, sex domicile status, socio-economic status, personal hygiene, occupation, diet and residential sanitation.
|Age Groups||1 - 10||4||10||14||7.38
|11 - 20||11||4||15|
|21 - 30||3||3||6|
|31 - 40||3||2||5|
p > 0.05
p > 0.05
|Religion||Hindu||19||19||38||χ2 not applicable as expected frequency<5|
p > 0.05
|Occupation||Student||13||16||29||χ2 not applicable as expected frequency<5|
p > 0.05
Table 8: Comparison of demographic profile in different study groups.
Total relief was seen in patients treated with Embelia in relation to Fatigue, Anal pruritis, and Anemia. Some symptoms i.e. Anorexia (25%), Loss of Appetite (23.07%), Dizziness (20%), Pain abdomen (20%) persisted. Patients treated with Mallotus had relief with Diarrhoea, Anorexia, Fatigue, Pruritis, Anemia, Loss of appetite, Hypopigmented skin patches with persisting symptoms with regards to Anal pruritis (25%) and Dizziness (11.11%) (Table 9).
|Specific symptoms||Group A||Group B|
|B.T.||A.T. (persisting)||B.T.||A.T. (Persisting)|
|Loss of appetite||13||(65%)||3||(23.07%)||13||(65%)||1||-|
|Hypopigmented skin patches||-||-||-||-||2||(10%)||-||-|
Table 9: Effect of trial drugs on Clinical Signs and symptoms of (%)Intestinal parasites (n = 20).
In patients treated with Embelia it was observed that there was persistence of ova/cyst in patients positive for Giardia and Taenia, 50% persistence with Ancyclostoma and Entamoeba, and 37.5% persistence with Ascaris and 33.3% with Hymenolepis nana. While those with Mallotus there was persistence of ova of Ascaris in only 12.5% of the patients and Entamoeba in 25%. Rest showed negative report after treatment (Table 10).
|Ova/cysts||Group A||Group B|
|B.T.||A.T. (Persisting)||B.T.||A.T. (Persisting)|
α. Ascaris + Giardia
β. Ascaris + trichuris
χ. Cyclospora + Idamoeba
δ. Ascaris + Taenia
Table 10: Persistence of ova/cyst (%) after treatment with drug A and drug B (n = 20).
The cure rate was 40% in Embelia treated group with improvement in 35% and no improvement in 25% of the cases. While 70% of the cases treated with Mallotus were cured with improvement in 15% of the cases and no improvement in other 15% of cases (Table 11).
|Response of the Drug||Embelia||Mallotus|
Table 11: Overall response of Embelia and Mallotus (%) (n = 20).
Table 12 shows that the initial mean ± SD for Embelia Group was 10.37 ± 0.97 and after a month’s drug therapy it increased to 11.55 ± 0.81. The improvement of Hb gm% was statistically highly significant (p<0.01) while in Mallotus Group initial mean ± SD was 10.30 ± 0.78 and after treatment it increased to 11.08 ± 0.63. The improvement of Hb g% was statistically significant (p<0.01). No significant difference was observed between both the groups, when intergroup statistical comparison was done.
|Groups||BT||F1||F2||F3||F3–BT||Paired ‘t’ test|
|Embelia (n = 20)||10.37 ± 0.97||11.23 ± 0.92||11.45 ±0.81||11.55 ± 0.81||1.175 ±0.92||t = 5.70 p<0.01||NS|
|Mallotus (n = 20)||10.30 ± 0.78||10.88 ± 0.72||11.00 ± 0.63||11.08 ± 0.59||0.775 ± 0.752||t = 4.61 p<0.01||NS|
|Group||‘t’ value||‘p’ value|
|Embelia Vs Mallotus||1.51||p>0.05 NS|
Table 12: Change in blood Hb g% before and after treatment in both groups (n = 20).
The above data shows that the initial mean of eosinophil count is 8.35 ± 4.45, which decreased to 2.94 ± 0.90 in Group A. It was statistically significant. Group B also showed statistically significant result. Difference among the study groups was not statistically significant (Table 13).
|Groups||BT||F1||F2||F3||BT Vs F3||Paired ‘t’ test|
|Embelia||8.35 ± 4.45||4.65 ± 2.06||3.53 ± 1.18||2.94 ± 0.90||6.00 ± 4.20||5.89 p<0.001||HS|
|Mallotus’||7.40 ± 3.52||4.78 ± 2.29||4.00 ± 1.33||3.56 ± 1.29||4.39 ± 3.16||5.88 p<0.001||HS|
|Group||‘t’ value||‘p’ value|
|Embelia Vs Mallotus||1.29||p>0.05 NS|
Table 13: Response of treatment on eosinophil count (%) in Embelia and Mallotus (n = 20).
On the basis of the findings recorded in the clinical cases it is evident most of the patients belonged to age group between 11-20 years, majority of patients were males and belonged to rural area. The incidence of disease was more in patients with poor hygiene i.e. improper cleaning of hands after defaecation or before meals. Vegetarians and non-vegetarians were equally affected; this may be due to food borne infections commonly transmitted by the ingestion of ova and cysts attached on raw vegetables and improperly cooked meat and uncooked vegetarian meals.
Patients treated with Embelia robusta had a cure rate of 40%, improvement in 35% and no improvement in 25%. Patients who received Mallotus showed better response with cure rate of 70%, improvement in 15% and no improvement in 15%. There was statistically significant increase in Hbg% and decrease in eosinophil in both groups.
No adverse effects were observed with either of the drugs.
Hence, it can be concluded that comparatively Mallotus has a better clinical response over Embelia robusta. The accepted species is Embelia ribes Burm. While Embelia robusta is the substitute. Looking into the market dominance Embelia robusta was chosen for the study. A study comparing the actual species Embelia ribes is recommended as it is said to be the best for all infective pathogens. Also the study is to be performed on large number of patients.