Effect of oral administration of Terminalia chebula on gastric emptying: an experimental study.MD Tamhane, SP Thorat, NN Rege, SA Dahanukar
Ayurveda Research Centre, Department of Pharmacology, Seth GS Medical College, Parel, Mumbai.
Terminalia chebula is a commonly advocated agent in Ayurveda for improving gastrointestinal motility. Charles Foster rats (150-200 gms of either sex) were divided into four groups as follows--Group 1 (n = 15) normal animals; Group II (n = 6) rats administered metoclopramide (1.35 mg/kg); Group III (n = 8) rats given atropine (0.45 mg/kg). These agents were injected intramuscularly, 30 mins before the experiment. Rats from Group IV (n = 8) were administered Terminalia chebula (100 mg/kg/day for 15 days orally). Metoclopramide and atropine have established prokinetic and antikinetic activities respectively and are therefore included for comparison. All rats were then given a test meal of methyl cellulose (1.5%) mixed with phenol red (50 mg/100 ml) orally and gastric emptying was measured 20 mins later. Gastric emptying of normal rats (Group I) was found to be 51.6 +/- 7.79%. Metoclopramide significantly increased the gastric emptying (76.33 +/- 12.37%; p < 0.01) and atropine inhibited the motility (% gastric emptying being 7.26 +/- 19.76%; p < 0.01). Terminalia chebula was found to increase the percent gastric emptying (86.57 +/- 6.65%; p < 0.01). Thus from this study it appears that Terminalia chebula can serve as an useful alternative to prokinetic drugs available today.
Keywords: Animal, Atropine, pharmacology,Comparative Study, Dopamine Antagonists, pharmacology,Female, Gastric Emptying, drug effects,Male, Medicine, Ayurvedic, Metoclopramide, pharmacology,Parasympatholytics, pharmacology,Plant Extracts, pharmacology,Plants, Medicinal, Rats,
Gastroparesis is one of the troublesome complications of long-term diabetes, anorexia nervosa and scleroderma. Some of the unpleasant sequelae following gastric surgery have been attributed to changes in gastric emptying. A number of commonly prescribed drugs are also known to decrease gastric emptying. Atropine and its various derivatives, antidepressants like imipramine and antihistaminics have been found to possess antikinetic effects. Gastric emptying has also been shown to be markedly delayed in women given pethidine, diamorphine and pentazocine during labour. In order to relieve the resultant symptoms of gastroparesis like feeling of fullness, belching, nausea and discomfort, prokinetics or drugs which improve gastric emptying are in demand. The current research in this field is focussed mainly on metoclopramide and domperidone (dopamine receptor antagonists) and cisapride (5-HT4 agonist).
Ayurveda, the traditional medical system of India cites drugs like Picrorrhiza curroa, Emblica officinalis, Ricinus communis and Terminalia chebula for correcting disturbances of gastro-intestinal motility (6). Of them, Terminalia chebula (family-Combrataceae) is the most widely used agent in practice and is also an ingredient available in combination with a number of OTC products, prescribed to improve gastrointestinal motility (e.g. Gandharvharitaki, Triphala, Abhayarishta etc).
The effect of this plant on intestinal motility has been evaluated by Miglani, et al using charcoal as a marker. A diligent literature search however failed to show any scientific documentation of the effect of this drug on gastric motility. Therefore the present study was conceived to find out the effect of chronic oral administration of Terminalia chebula on gastric emptying.
This study was carried out in 37 Charles Foster rats of either sex weighing between 150-200 gms. These were divided into four groups as shown below:
1. Group I (n=15). These rats did not receive any drug and served as a normal control group.
2. Group II (n=6). The animals from this group received metoclopramide 1.35 mg/kg intramuscularly 30 mins before the experiment.
3. Group III (n=8). Atropine 0.45 mg/kg was administered intramuscular 30 mins before the experiment.
4. Group IV (n=8). These rats received Terminalia chebula 100 mg/kg/day orally for 15 days prior to assessment of gastric emptying. The fruits of Terminalia chebula were pulverised and a decoction of the powder was prepared in distilled water. It was administered orally in the dose of 100 mg/kg in the morning. The time of administration was kept constant for all the 15 days.
The animals were kept fasting for 18 hours prior to the experiment but were permitted water ad libitum. On the day of the experiment, animals belonging to groups II and III received the appropriate drug. The animals from Group IV did not receive the drug on the day of the experiment.
Gastric emptying was measured by the method of Scarpignato, et al In brief, the animals were administered a semisolid test meal (1.5 ml) of methyl cellulose (1.5%) containing phenol red as a marker (50 mg/100 ml). Immediately after the test meal (0 mins), one animal from each group was sacrificed by cervical dislocation. This animal served as the standard control for its own group. The rest of the animals from each group were sacrificed 20 mins after administration of the test meal. Laparotomy was performed. The stomach was clamped at both, the cardiac and pyloric ends, and removed in toto without opening it. The stomach surface was washed with normal saline, transferred to 100 ml of 0.1N NaOH, cut into pieces and homogenised. The solution was allowed to settle at room temperature for 60 min, following which 5 ml of the supernatant was added to 0.5 ml of trichloroacetic acid (20% W/V) and centrifuged at 2800 rpm for 20 min. The supernatant of the centrifuged mixture was added to 4 ml of 0.5N NaOH. The colour developed due to phenol red in this mixture. Using a spectrophotometer at a wavelength of 560 nm the concentration of phenol red was determined. The gastric emptying was calculated by the formula :
% Gastric emptying = 1 - —— x 100
X = Amount of phenol red present in stomach homogenate from test animal.
Y = Amount of phenol red recovered from standard animal (sacrificed at 0 min following test meal).
Statistical analysis: Student’s unpaired ‘t’ test was used to compare the findings of various groups.
The % gastric emptying in normal rats after 20 mins of the test meal (group I) was 51.6 +/- 7.79%. The % gastric emptying of the rats injected with metoclopramide 30 mins before the test meal was found to be 76.33 +/- 12.37%. This was significantly more as compared to Group I (p<0.01).
Gastric emptying was markedly reduced to -7.26 +/- 19.76% (p<0.01) in the group receiving atropine (Group III) as compared to the normal control. Terminalia chebula increased % gastric emptying to 86.57 +/- 6.65% (p<0.01 as compared to Group I). Further, this was comparable to the values of % gastric emptying obtained for Group II.
Several prokinetic drugs like metoclopramide and cisapride are used for the treatment of diseases associated with delayed gastric emptying. However their use is limited by an array of side effects, which occur as a result of their widespread actions.
A mention is found in Ayurveda regarding the use of Terminalia chebula in disorders of gastrointestinal motility. Therefore we carried out this study to evaluate the effect of Terminalia chebula on gastric emptying. While planning the study, metoclopramide - a prokinetic drug and atropine - a known antikinetic agent were incorporated in the study design. These agents served as tools to validate the model used to evaluate gastric emptying and also to compare the effects of Terminalia chebula.
As there is no pharmacokinetic data available with regards to Terminalia chebula, chronic administration for 15 days was preferred to ensure adequate concentration of the agent in the body. On the other hand, both the standard agents used for comparison are known to attain therapeutic concentration within 30 min of oral/parenteral administration. The parenteral route was selected in this study because the experimental procedure demands 18 hours fasting prior to the administration of the test meal.
The effects of metoclopramide and atropine on gastric emptying were as per the expectation. Metoclopramide increased the percent gastric emptying significantly as compared to the normal values whereas atropine reduced it.
Our study showed that Terminalia chebula significantly increased gastric emptying. The enhancement of gastric emptying was comparable to that produced by metoclopramide. This indicates that Terminalia chebula can be an useful alternative to the prokinetic drugs available today.