Effect of Asparagus racemosus (Shatavari) on gastric emptying time in normal healthy volunteers.
Asparagus racemosus (Shatavari) is used in Ayurveda for dyspepsia (amlapitta) and as a galactogogue. It was hence compared with a modern drug, metoclopramide, which is used in dyspepsia to reduce gastric emptying time. Gastric emptying half- time (GE t1/2) was studied in 8 healthy male volunteers using a cross-over design. The basal GE t1/2 in volunteers was 159.9 +/- 45.9 min (mean +/- SD) which was reduced to 101 +/- 40.8 min by Shatavari (p less than 0.001) and to 85.3 +/- 21.9 by metoclopramide (p less than 0.001). Metoclopramide and Shatavari did not differ significantly in their effects.
The powdered dried root of Asparagus racemosus (Shatavari) is used in Ayurveda for dyspepsia (amlapitta or acid regurgitation) and to increase milk secretion in a lactating woman. A mixture 'Lactare', containing Asparagus racemosus as its major component, has been reported to cause significant rise in scrum prolactin levels. The alcoholic extract of Asparagus racemosus has been shown to increase the prolactin levels in female rats.
Metoclopramide, a dopamine receptor antagonist with a poor penetration of the blood-brain barrier, is used in radiology and in patients with dyspepsia to increase the rate of emptying of the stomach, and also causes increase in milk secretion by increasing prolactin levels,.
With a working hypothesis that the therapeutic effects of Asparagus racemosus may be due to a principle containing dopamine receptor antagonist activity, we decided to compare Shatavari and metoclopramide for their effects on gastric emptying time.
This study was carried out in 8 normal healthy male volunteers aged 40 + 18.6 years (mean + S.D.). Each subject underwent physical examination and laboratory investigations to rule out anaemia, diabetes and any abnormality in renal and liver functions.
The study was accepted by the institution's ethics committee. Informed written consent was obtained from the volunteers.
After an overnight fast, subjects reported to the nuclear medicine laboratory at 8.30 a.m. on 3 occasions at 4 day intervals.
On the first day of the study, 25 ml of water was given and half an hour later, 2 radio-labelled jam sandwiches were given (60 gm of jam was mixed with 250-300 ?Ci of technetium 99m-labelled sulphur colloid, and applied over 4 slices of bread).
The test meal was given along with 100 ml of water. On the next 2 visits, subjects received 2 gm of powdered root of Shatavari, or a 10 mg tablet of metoclopramide according to a randomisation scheme. Drug administration and recording of gastric emptying rate was done by different investigators.
After the test meal, subjects were made to lie supine under a Picker Dyna-4 gamma camera having a computer on-line (MDS-A2, Meditronic). The stomach was identified by its configuration on the image screen, and the whole stomach (fundus to pylorus) was selected for scanning. Counting was done manually as well as by a computer. Counts were recorded for 30 sec every 5 minutes, till the counts reached half of their initial value, or upto 3 hours after administration of the test meal, whichever was earlier.
Gastric emptying time was by a linear regression of counts/30 seconds Vs time in on an IBM PC using a created by program Lotus 1-2-3.
Statistical analysis was carried out by a 2-way analysis of variance, followed by a Neuman-Keuls modification of the Studentised range.
To evaluate the central dopaminergic effect of Asparagus racemosus, a preliminary study was carried out in male rats weighing 100-120 gm. Three groups of animals (10 in each group) were taken; the first group served as a control, receiving 1 ml distilled water orally, the second and the third groups were treated with 1 gm/kg and 2 gm/kg of Asparagus racemosus orally respectively. The animals were observed at 1/2 hourly intervals for 4 hours, and after 24 hours.
As shown in [Table - 1], we found that both Shatavari and metoclopramide significantly reduced gastric emptying halftime. The difference between Shatavari and metoclopramide was not statistically significant.
Analysis of the results was performed using a 2-way analysis of variance and finding the F ratio for variance due to treatment differences. This turned out to be highly significant (17=29.9 for 2, 14 d.f., p < 0.001) [Table - 2] and hence a comparison between individual treatments was performed using a Neuman-Keuls modification of the Studentised range. This showed significant differences (p <0.01) between control and metoclopramide, and between control and Shatavari.
In the experiment in rats, Shatavari in doses of 1 gm/kg and 2 gm/kg did not produce catalepsy or sedation.
Dopamine released within the walls of the stomach as an endogenous neurotransmitter is known to impede gastric emptying,.
The present study was undertaken as a part of a project to identify indigenous drugs with antidopaminergic activity. The dried root of Shatavari (Asparagus racemosus) is used in Ayurveda for both relief of amlapitta and shoola (dyspepsia) and to increase milk yield in lactating women. Metoclopramide is a synthetic dopamine antagonist, which is used in therapy as an antiemetic and antidyspeptic agent. The side effect, galactorrhea caused by dopamine antagonists has long been documented,. Both metoclopramide and Shatavari increase prolactin levels,,,. Hence, we hypothesised that Shatavari may be a mild dopamine antagonist, acting in a way similar to metoclopramide.
The increased prolactin levels and the consequent galactorrhea seen with doparnine antagonists are observed even with those antagonists with poor CNS penetration such as metoclopramide, since the pituitary lies outside the blood-brain barrier. Dopamine itself has been confirmed to be the factor inhibiting prolactin release.
Central dopamine antagonists cause catalepsy in animals. In a preliminary experiment, we were unable to elicit catalepsy in rats with Shatavari even with massive oral doses (2 gm/kg) suggesting that its action may be outside the blood-brain barrier, similar to that of metoclopramide.
As there are no simple experimental models to evaluate peripheral dopamine antagonists, and autoradiographic receptor binding studies were not available to us, we decided to test our hypothesis from two viewpoints viz. whether the clinical use of Shatavari in dyspepsia was justified and whether its action was similar to metoclopramide.
We found that the effect of Shatavari on gastric emptying was comparable with metoclopramide, and its traditional use in dyspepsia may be justifiable. The usefulness of any potential antidyspeptic drug may therefore possibly be predicted from its effect on gastric emptying. As Shatavari accelerates gastric emptying rate, further studies are in progress in dyspepsia patients.
The present study does not prove the mechanism of action of Shatavari. It is merely supportive of the above hypothesis and suggests a fruitful avenue of research for those involved in indigenous drug research with facilities to carry out receptor binding studies with purified subfractions of Asparagus racemosus.
We thank the Dean, Seth GS Medical College and King Edward Memorial Hospital, for permission to carry out this study; the Research Society, King Edward Memorial Hospital for financial assistance and Dr. GH Tilve, Professor & Head, Dept. of Medicine & Nuclear Medicine for permitting us the use of facilities of the Nuclear Medicine Laboratory.