Comparative study of double blind clinical trial in side-effects among Areca catechu l., Thai traditional herbal formula and mebendazole

Abstract

Background:

This study was carried out in Mahasarakham Primary Healthcare Center, Mahasarakham province in the area of Northeastern of Thailand. The experiment was randomized control trial clinical study in order to examine the side effects of Areca catechu Linn., Thai traditional formulae medicine, mebendazole in the treatment of anti-helmintic activity of mixed worms infection in human.

Materials and Methods:

The experimental group consisted of 15 patients and 5 patients for control group with inclusion and exclusion criteria, which were screened by parasitologist with the selection of mixed worm infection patient samples. The investigation of side effects was recorded after the treatment of each group of patient with different kinds of 4 group of medicine.

Results:

The percentage of side effects was collected by nurses and confirmed by the physician at Mahasarakham Health Center, which were diarrhea and nausea side effects. The percentage of side effects by the treatments of Areca catechu Linn., Thai traditional formulae medicine, mebendazole were investigated by the physician and the pharmacist, which the result showed 20% of diarrhea in Areca catechu Linn., 20% of nausea in Areca catechu Linn, 20% in side effect of diarrhea in mebendazole treatment, and no side effects were found by the treatment of TTFM. The result showed that Areca catechu Linn. had higher side effects among the 3 anti-helmintic drugs.

Conclusion:

The findings indicate to increase the numbers of samples of worm-infected patients, which the samples can be identified with the specification of helminthes genus and species in order to obtain the efficacy by the treatment using Areca catechu Linn and also indicates to increase various forms of dosage preparations and various demographic locations in Thailand.

INTRODUCTION

In the tropical countries such as Thailand, we have a high incidence rate of human parasitic infection, which can be very harmful to humans. The initial stage of parasitic infection such as nematode, tapeworm, hookworm do not have sudden severe harmful effects to the human body. The symptoms will develop gradually and slowly, which can destroy the internal organs. Some parasites can withdraw blood from human intestines or other internal cell wall organs and also nutrients from human bodies. The patients will slowly lose their weight and turn pale. The patients will also possess a lack of cognitive thinking and less intellect.

Over 32 countries faced the problems of clean food consumption and clean drinking tap water management supplied to the main population. There are over 12 million people who suffer from helminthes infection.

WHO (World Health Organization) has considered the parasitic problem as one of the major health communicable disease issues in the world. In Thailand, the Ministry of Health has launched the project in order to decrease the incidence of foodborne diseases, especially parasitic diseases, which occurred in people who have less exposed to sanitation of food and water intake. Normally, these patients will contact the parasites through food intake, water intake, and skin transmission. One cause is the style of Thai Northeastern food preparation, which involves undercooked foods. The villagers like to consume raw food from fish, pork, beef, which promote worm diseases. Another reason is polluted local drinking water that the people consume on a daily basis from the river, which was is clean and is contaminated with bacteria, worms, and viruses. WHO is responsible for the record of 133 million of infected worm diseases patients throughout the world. The indication showed that the numbers of infected patients were under the age below 5 years mostly. Since 2006-2011, the incident rate of parasitic human diseases was decreased gradually from 1,051,447 to 800,000 patients.

The worms which were discovered in Thailand were multicellular and one structure. Helminthes live in human body and also in animal body. They work as possible parasitic condition consuming the nutrients and blood from the body. There are many species of parasites, which live in soil, weed, water in the fresh of terrestrial, in aquatic and in amphibians etc. Helminthes can transmit through oral skin absorption and even through placenta movement from mother to baby. Helminthes are tapeworm, Strongyloides, liver flukes, lung flukes and some may be travel through skin such as Trichunoris.

The patients who are infected may show symptoms as more food intakes, weight loss, diarrhea, irritable colon, bloating, body pain, blurred vision. The patients should go to see the physician in order to have stool examination test for worm eggs per gram of feces by any method such as Kato Katz method or ether – formalin sedimentation test method. Some patients have shown severe symptoms, which cause paralysis or death. Types, size, volumes, and location of helminthes and also the duration of infection are important for indicating the severity of infection. Some patients exhibit signs of jaundice, liver cirrhosis and result in liver carcinoma.

The side effect of anti-helminthic medicines may cause stomachache, diarrhea, and irritable colon. Some also cause nausea, vomiting. The research team had introduced Thai traditional formula medicine (TTFM) in the treatment of helminthes and compared the efficacy and side effects among mebendazole (500 mg) and Areca catechu Lin.

Thai traditional formula medicine consists of 8 herbals, which are

1. Terminalia chebula (Retz) (SamaoThai)^F1.

2. Terminalia Citrina (Roxb.) (Samao Ted) (Arjun).

3. Curcuma zedoaria (Berg) Rosco. (Kamin Aoi)^F2.

4. Terminalia Citriva (Gaertn). Roxb. Flem (Samao Ngu).

5. Cuttle Bone (Tricosan) (Lintalay).

6. Purified water.

7. Croton tiglium Lin. (Purging croton)^F3.

8. Diospyros mollis (Griff.) (Ebony tree)^F5.

Dosage of TTFM is orally, 3-6 capsules daily before breakfast (500 mg), continue for 3 days. Each of 7 medicinal herbs and purified water is mixed as dry powder in equal portions and is filled into capsules.

Mebendazole 500 mg is the drug of choice in treatment of helminthes infection in this research and is considered as modern medicine. Dosage form is chewable tablet, 500 mg, and taken as once-daily for 3 days continuously.

Areca catechu Lin. was prepared for herbal medicine in the treatment of mixed anti-helminthes infection. Dosage was 60-90 mg in dried powder capsules and taken by mixing with syrup water as once-daily for 3 days continuously. All medicine were tested to meet the standardization quality with free from bacterial or foreign contamination, free from steroidal substance, and free from pesticide from the Department of Oriental Medicine, Rungsit University, Thailand.

MATERIALS AND METHODS

This research was proceeded during September, 2011 at Primary Health Care Center Mahasarakham Hospital, Mahasarakham, Thailand. The samples were screened purposively relevance to the inclusion and exclusion criteria of 16-65 years old with both genders males and females (not pregnant), non-medicated with any of anti-helminthic drugs, non-medicated with any of antibiotic, phenytoin, carbamazepine, no complication of gastrointestinal symptoms, no hepatitis or liver diseases. The collected samples were divided for 5 patients in each group for 4 groups as follows: Placebo control group, treated with mebendazole ^F6experimental group, treated with Thai traditional herbal formula (TTHF) experimental group, and treated with Areca catechu Lin. experimental group.

The screening method used in this experiment was ether formalin stool sedimentation examination, which could be used to identify and quantify the EPG (numbers of eggs per gram of feces of infected patient). The study was randomized control trial in the comparative study of the efficacy and side effects. Efficacy was comparable with the % reduction of EPG in each group treated with mebendazole, Areca catechu, and TTHF medicine.

Preparation of Thai traditional herbal formula (TTHF) Thai traditional formula medicine consists of 8 herbals, which are.

1. Terminalia chebula (Retz) (SamaoThai)^F1.

2. Terminalia Citrina (Roxb.) (Samao Ted) (Arjun).

3. Curcuma zedoaria (Berg) Rosco. (Kamin Aoi)^F2.

4. Terminalia Citriva (Gaertn). Roxb. Flem (Samao Ngu).

5. Cuttle Bone (Tricosan) (Lintalay).

6. Purified water.

7. Croton tiglium Lin. (Purging croton)^F3.

8. Diospyros mollis (Griff.) (Ebony tree)^F5.

TTHF was prepared from 7 herbs as listed from the above. Firstly, we extracted Terminalia chebula (Retz) (SamaoThai)^F1 by boiling the immature fruits of 1 with portable water and dried it with the spraying technique in order to obtain dry powder of Terminalia chebula (Retz) (SamaoThai)^F1.

Then, we repeated the same process of extraction with Terminalia Citrina (Roxb.) (Samao Ted) (Arjun), Terminalia Citriva (Gaertn). Roxb. Flem (Samao Ngu) to obtain the purified dry powder of Terminalia Citrina (Roxb.) (Samao Ted) (Arjun), Terminalia Citriva (Gaertn). Roxb. Flem (Samao Ngu). Then, we took the underground stem of Curcuma zedoaria (Berg) Rosco. (Kamin Aoi)^F2 and grated it. The grated Curcuma zedoaria (Berg) Rosco. (Kamin Aoi) was blended in very fine powder. The cuttle bone was triturated as very fine powder. Then, we took the seed of Croton tiglium Lin. (Purging croton)^F3 and triturated as fine powder. We took the fresh fruits of Diospyros mollis (Griff) (Ebony tree)^F5 and sliced them to very thin pieces and triturated as the fine powder, then mixed it with coconut milk and dried with spray drying technique. Each of them was weighed equally and mixed together with the amount of 72 mg in each prepared dried herbal powder and were filled in 500 mg aseptic capsules by using encapsulation method. All herbs were collected with uncontaminated of bacteria, heavy metals, viruses, and free of pesticides with adequate cleansing methods. They were passed through Gamma – rays for aseptic purposes. The process for preparation and purified of all sample capsules were also tested for quality control at the Faculty of Oriental Medicine, Rungsit University, Thailand to assure quality, safety in production. Therefore, the products were free from any toxicity. TTHF (500 mg) contained 7 plant species as mentioned above used for anti-helmintic formulae in this experiment.

Areca catechu Linn.^F4 Preparations: In this experiment, we used Areca catechu Linn. (Betel Nut) seeds in order to prepare anti-helminthic medicines. We have chosen the brownish-white color derived from thin sliced pieces of the nuts, which have a high qualitative content of arecoline as one of the active ingredients in anti-helmintic action of Areca catechu Linn. The betel nut seeds were weighed between 60-90 grams, and then triturated as a very fine powder. The powder was mixed with the syrup water for oral administration. The dosage suggested was taken in syrup once-daily for 3 days before breakfast.

RESULT

The result of the experiment after treating 20 patients with placebo, mebendazole, Areca catechu L. and TTHF showed that the side–effects of mebendazole had 20% of diarrhea while Areca catechu L. had 20% of diarrhea and 20% of stomach discomfort and nausea. There were not found any side–effect in treatment with TTHF.^T1

CONCLUSION AND SUGGESTIONS

This study carried out 3 days dosages and the % EPG reduction was collected after the 4^th day of the experiments in each group of samples. There may be some variations in the results after the first dosage given of each vermicidal medicine. The differences in the efficacy can be attributed to the different locations of the parasites such as blood stream lung liver. Therefore, the efficacy was different in different species of helminthes. The extensive study should be recommended in various dosages, and repeated dosages of 7 days, 14 days, and 20 days should be measured the end result of % reduction of eggs per gram of feces (EPG). The result would be more reliable, which was suggested to increase the size of samples and dosages. The suggestion also aimed to investigate future research of specific species of helminthes for comparative efficacy and also suggested to study in different demographical locations in Thailand.