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Afr. J. Biomed. Res. 13 (September 2010); 197 - 206

Research article
Effect of an Aqueous Extract of Entandrophragma utile
Bark on Gastric Acid Secretion in Rat and Isolated Ileum
Contractility in Guinea pig
John T. A and Onabanjo A. O.
Department of Pharmacology, Lagos State University College of Medicine, Lagos.

ABSTRACT: Adjunct therapy is needed for patients with compromised gastrointestinal mucosa due to necessary aspirin usage
against cardiovascular disorders. We tested the Nigerian bark extract of Entandrophragma utile on gastric acid secretion (GA)
and peptic activity (PA). Rats were ligated at the pylorus for collection of gastric juice which was measured for PA
spectrophotometrically using bovine serum albumin as substrate and for titratable GA using phenol red indicator. The extract
was compared with ranitidine (histamine H2-receptor antagonist). The extracted was tested on isolated guinea-pig ileum
preparations for histaminergic responses and was compared with mepyramine (histamine H 1-antagonist). E. utile reduced GA
to 1.33 + 0.6 uEq g-1 from 2.82 + 0.7 uEq g-1 in controls using 6h ligations. For 4h ligations, control PA (mg/dL BSA digested)
was 38.75 + 4.05 which was lowered to 14.8 + 4.67 (p<0.01) by the extract and to 3.4 + 0.72 (p<0.001) by ranitidine. Chronic
administration of E. utile decreased GA in 4h collections. E.utile, 10 -160 x 10-3 g, antagonized 10 µg histamine-induced
contractions by 28-62% dose-dependently. Mepyramine gave a parallel shift of the histamine dose-response graph to the right
typical of a competitive antagonism. E. utile extract gave a non-parallel shift to the right with a lowering of maximal response
typical of a non-competitive antagonism. The two properties of the E. utile extract on acid and pepsin may be valuable for
patients on aspirin with compromised mucosa therefore the extract could be developed as adjunct therapy to minimize
aggravation of mucosal damage by acid-peptic autodigestion.

Keyword: Entandrophragma utile, peptic ulcer, stomach acid, peptic activity, antisecretory, Shay rat

INTRODUCTION ulcers are especially associated with hypersecretory

1
states (Richard, 1985). Treatment of peptic ulcers aims
at buffeting defense and integrity of the mucosa and
It has long been known that gastric acidity and limiting the influence of acid and pepsin. Both the
enzymatic activity of pepsin are major culprits hydrochloric acid and pepsinogen secreted by the
generating ulceration in the compromised gastric glands (McMinn and Hobdell, 1974) are
gastrointestinal mucosa (Gunzburg, 1852, Beaumont, important for normal digestive function. However, for
1883). Hypersecretory states may lead to autodigestion ulcer patients, it may be desirable to inhibit such
of the gastric mucosa and painful ulceration. In fact, secretion. In recent times the use of aspirin as an
Quincke (1882) introduced the term “peptic ulcer” to important cardio-protective, especially in elderly
describe ulcers of the gastrointestinal tract. Duodenal persons, has surged because it has been observed to
prevent stroke, some forms of angina, vascular
thrombosis as well as other disease conditions. Aspirin
consumption was 40 billion tablets per annum
according to a 1989 report by Barrier and
Hirshchowitz. Non-steroidal anti-inflammatory drugs
(NSAIDs) such as aspirin have been known to cause
*Address for correspondence: [email protected] peptic ulcers for a long time (Lang, 1957; Levrat and
Phone: 234 7028338910 Lambert, 1960). Aspirin, both by being a COX-1
inhibitor and a generator of toxic oxygen metabolites,
Received: February, 2010; Accepted: August, 2010
compromises gastrointestinal mucosal integrity. A new
breed of peptic ulcer patients have been generated by
 Entandrophragma utile and gastric acid secretion
the increased use of aspirin therefore there is need for filtrate. The resultant filtrate was stored in stoppered
development of adjunct therapy to prevent the flasks in a refrigerator at 40C for not more than two
ulcerogenic side effect of this important drug (Anand weeks after which the extracts were discarded and fresh
et al., 1999). The aqueous bark extract of ones prepared. The doses of extract given were
Entandrophragma utile is used in Nigerian traditional expressed in gram per kilogram body weight (g kg -1).
medicine to treat gastrointestinal ulcers (John and
Onabanjo, 1990a and 1990b, John 1994). This report Animals
shows its effect in inhibiting gastric acidity and peptic Male and female Sprague-Dawley rats weighing 200 +
activity in Shay rats. 20 g were obtained from the Laboratory Animal Centre
(LAC), College of Medicine, University of Lagos
(CMUL) and utilized according to ethical approval by
MATERIALS AND METHODS the LAC. Food was withdrawn overnight before
experiments. During food withdrawal, animals had
Collection and extraction of plant material access to water ad libitum and were kept in wide-mesh
Fresh pieces of the bark were obtained from a tree in its bottom cages to prevent coprophagy. They were sex
natural habitat at Ojokoro, on the outskirts of Lagos, and weight matched between groups per experiment.
Nigeria with the help of an experienced traditional
herbalist, Chief E. O. Esho. The botanical profile was Shay rat preparations
confirmed at the Forestry Research Institute of Nigeria, Anesthetized rats were ligated at the pylorus as
Ibadan with the support of a taxonomist, Dr. M. O. described by Shay et al. (1954) in order to collect
Soladoye. The fresh bark was used within a week of secreted gastric acid and pepsin. Each rat was
collection. If not used on the day of collection, it was anaesthetized lightly in an ether chamber. A midline
kept in refrigeration at 40C. Before use, the bark was incision of about 2cm extending from the xiphoid was
chopped into pieces of about 1 cm3 and rinsed properly made on the ventral abdominal wall to expose the
in water. According to Chief Esho, about 200 g of abdominal cavity. A ligature was placed at the junction
chopped bark is simmered for 2 h in about 1L water at between the pylorus and duodenum with care being
about 950C. We adapted this to glass sohxlet flask taken to avoid damage to the gastro-duodenal artery or
extraction which allows a constant volume of solvent to traction on the stomach. A No. 8 polyethylene tube
be used throughout the extraction and this improves was carefully passed through the oesophagus into the
calculation of both concentration and yield of extract stomach with the tip impinging on the stomach wall.
from the original starting materials measured with Gastric lavage was carried out through the tube to
precision each time. remove food residues and gastric secretions. Four
The extract was then decanted and filtered while milliliter of physiological saline was injected and
hot with Whatman filter paper No. 1 and then cooled to withdrawn immediately by gentle suction with a 5ml
room temperature (30 + 20 C) in a stoppered flask. The syringes while gradually withdrawing the tube. The
volume of the extract was measured and the pH tube was passed the second time into the stomach to
determined using a pH meter (Seibolo Wien, Australia). recover any fluid that might still be there, and was
The used bark was then dried and re-weighed for subsequently removed (a total of 4ml or more was
calculating the extract derived from it. The recovered). The opened abdominal wall was
concentration of the extracts so obtained in the immediately closed by suturing and the area cleaned
procedures were calculated as a difference in the with physiological saline to remove blood stain.
weight of starting and used bark material per mililitre, Transparent lacquer (nail varnish) was used to coat the
(g ml-1). The tannin contents of the extract gave it a dried sutured surface area to prevent leakage and
reddish brown coloration and this posed a problem for ingestion of body fluids during grooming by the rat
phenol red assay of acidity therefore we decolorized the which invariably may affect the analysis of subsequent
extract although we did not know if the tannic content gastric effluents. After the operation, 5ml of 0.9%
contributed to any pharmacological effect of the NaCl was injected subcutancoulsy (s.c.) to make up for
extract. Activated charcoal (5 g) was mixed with 1 L the loss of body fluid during the process of the
of the extract and this was then stirred for 15 min over operation. The rat was left in a clean cage without
0
a hot plate (50 C). It was left at room temperature for 1 food, water or ingestable materials to recover from the
h to allow binding of tannins. It was then filtered hot anaesthesia. After 4h accumulation of gastric secretion,
with Whatman filter paper No. 1. The filtrate was re- the rat was sacrificed by stunning once. The abdomen
filtered, if necessary, using Whatman filter paper No. 5 was again opened and a ligature placed on the
until the charcoal had completely disappeared from the oesphago-cardiac junction to prevent leakage of the
198 Afr. J. Biomed. Res. Vol. 13, No. 3, 2010 John and Onabanjo
 Entandrophragma utile and gastric acid secretion
acid effluent during excision of the stomach from the protein was read in a Pye Unicam SP6-450 UV/VIS
oesophagus and the duodenum. The stomach was then spectrophotometer (Phillips, England) at 700 nm.
removed, washed in physiological saline and dried with The second method used for the measurement of
filter paper. An opening was thereafter made along the peptic activity from the gastric contents of the stomach
greater curvature through which the gastric juice was of pylorus-ligated rats was that reported by Ohnishi and
drained into a 10ml measuring cylinder with a funnel. Barr (1978). The following reagents were used:
Reagent A or biuret reagent (Sigma U.S.A) contained
Analysis of gastric acid content 0.75 mmol l-1 CuSO4, 94 mmol l-1 NaOH, tartarate,
The gastric contents of each stomach were analyzed iodide and carbonate; Reagent B or Folin-Ciocalteau
individually. The contents were placed in centrifuge phenol reagent (Sigma, U.S.A) (this prepared reagent
tubes and centrifuged at 5000g for 20min in a Minor was standardized by the supplier and contained 2N of
Centrifuge (ESE, England) at room temperature (300C). Folin reagent); Reagent C or bovine serum albumin
After centrifuging, the supernatant fluid volumes (V E) (Sigma U.S.A) was the standard protein prepared as 1.5
and solid residues were recorded. If the residue mg ml-1 BSA in 0.01N HCl.
measured over 0.6 ml in the tube, the preparation was The preparation of the gastric acid filtrate up to
discarded because of contamination of the gastric hydrolysis was as in the Prino et al. method above and
effluent by coprophagy. The titratable acidity in the was used as the starting material in the present
supernatant fluid was then determined. Aliquots of 0.5 determination. To each cuvette was added 0.2ml
or 1ml of the supernatant fluid (depending on the gastric acid filtrate and 2.2 ml of reagent A. The tube
quantity obtained) were titrated against 0.1N NaOH contents were mixed thoroughly and left to stand at
using phenopthalein indicator. The titration was room temperature for 10 min. After this, 0.1ml of
duplicated where the volume of gastric effluent was reagent B was added and the tube contents were mixed
adequate. The titratable acidity was calculated as in immediately and left to stand for 30 min or longer at
simple volumetric analysis, and expressed finally as room temperature for colour development. The blank
micro-equivalent of titratable acid (H+) per kilogram cuvette contained 0.2ml saline instead of the gastric
fasting body weight of rat per 4h (μE kg -1 4h-1). acid filtrate and the other reagents were added as for
test cuvettes.
Peptic activity measurement The absorbency of the contents in the cuvettes were
Using the method of Prino et al. (1971) the enzymic read in a Pye Unicam SP6-450 UV/VIS
activity of pepsin in undiluted gastric juice was spectrophotometer (Philips, England) at 700 nm. The
measured using bovine serum albumin (BSA) as protein concentration was calculated from a standard
substrate. The principle is based on the proteolysis of curve. The test and blank were determined in duplicate.
the albumin substrate by gastric juice resulting in the
production of peptides which contain tyrosine and Standard curve
tryptophan whose relative density measured The standard curve for protein determination was
spectrophotometrically are indicative of the obtained by reconstituting in physiological saline
concentration of pepsin in the gastric juice. Conversely, reagent C which served as the stock solution. The latter
a reduction in the peptides represents an inhibition of was diluted in concentrations of 0, 25, 50, 75 and 100
proteolysis (antipepsin activity). mg l-1 of total protein. The prepared concentrations of
The gastric effluent collected was first centrifuged reagent C were mixed similarly as above with reagents
at 5000g for 10 min. A sample of 0.1 ml of the A and B in 3 ml cuvettes. The optical density was read
supernatant fluid was added to 1 ml of 0.5% BSA in at 725 nm and plotted against protein concentration.
0.01N HCl (pH 2). The gastric juice sample and BSA The protein concentrations of gastric juice samples
0
were mixed well and incubated in a water bath (37 C) were determined from the curve and used for the basic
for 20 minutes. A control cuvette containing gastric calculation of peptic activity.
juice was prepared and albumin was replaced with 1ml
0.01N HCL. The hydrolysis was brought to a stop after Test of the effect of E. utile extract or ranitidine on 4
20 min incubation by adding 2ml of 10% h gastric acid output (GAO) and peptic activity (PA)
trichloroacetic acid (TCA). All tubes were heated in Peptic activity (PA) and gastric acid output (GAO)
boiling water for 5 min, cooled and filtered through were determined as above. Determination of PA was
Whatman No.42 filter paper. To a sample of 2ml of the carried out before GAO measurement. PA was
filtrate was added 0.8ml of 2.5N NaOH and 0.2ml measured by both the method of Prino et al (1971) and
Folin-Ciocalteau reagent. The volume was made up to the method of Ohnishi and Barr (1978).
20ml with distilled water. The absorbency of the
199 Afr. J. Biomed. Res. Vol. 13, No. 3, 2010 John and Onabanjo
 Entandrophragma utile and gastric acid secretion
The three tests just described were run Measurement of the effect of the aqueous extract of
simultaneously using weight-matched rats on each E. utile on guinea-pigs ileum
occasion as follows: two rats for control given 1 ml Doses of 2-10 x 10-3 g of aqueous E. utile extract were
saline orally, two for treatment with 20 mg ranitidine in added to the organ bath alternating with 1-10-ug
1 ml orally, and two for treatment with 1ml of 100 mg histamine acid phosphate. Recordings were made
ml-1extract of E. utile given orally. Saline or test agent using a dose cycle of 3min with 20s contact time of the
was given immediately after ligation and animals were extract with the ileum.
sacrificed 4h post-ligation. The results of six
determinations were pooled at the end of the series. Determination of histamine responses with
increasing does of E. utile extract
Evaluation of gastric acid output for varying
ligation periods in rats treated with the E. utile The bathing Tyrode solution had 2 x 10-6g L-1
extract atropine added to block cholinergic receptors. A
Six male weight-matched rats were used in each bracketing assay was done using a
determination. Three were used as controls and were dose of 10 ug histamine. The extract, added to the
given 1 ml saline orally after ligation. The other three organ bath 30s before histamine, was used as the
were given orally 1ml of 100 mg ml-1 extract of E.utile antagonist and the response recorded. The response to
immediately after ligation. They were kept for 3, 5 and histamine alone was again recorded. The sequence was
6 h post-ligation respectively before being sacrificed. repeated using graded doses of the extract each time 10
The GAO measurement of gastric effluents was as -160 x 10-3 g with the constant dose of histamine (10
described above. The experiment was repeated for ug).
pooled sextuplate data.
Investigation of anti-histamine effect of the extract
Investigation of the effect of six weeks of E. utile
administration of E.utile extract on GAO and PA The ileum was bathed with atropinised Tyrode solution
Twenty rats were fed and kept normally for six weeks as above. Contractions of the tissue to 0.002 - 0.256 mg
during which they were given a suspension of 100 mg histamine were recorded to obtain a dose-response
ml-1 aqueous extract of E.utile to drink ad libitum in relationship. Then 5 x 10-6 M mepyramine, an H1
their feeding bottles. Fresh extracts were supplied in receptor-antagonist was also added before repetition of
their bottles daily in place of water. The rats were the histamine graded responses. Similarly, the E.utile
observed to drink freely and did not show any sign of extract (10 x 10-3 g) was added in place of mepyramine
displeasure to the drink. After six weeks, the rats were and the histamine responses were repeated. Ranitidine
tested for GAO as above. The PA determination was (40 ug) (Glaxo, Nigeria Ltd), an H2 receptor-antagonist
carried out by the Prino et al. (1971) method. was also added to the organ bath and the histamine
responses were recorded.
Investigation of the effect of E. utile extract on
histaminergic contractions of the guinea-pig ileum. RESULTS
Guinea-pigs of either sex weighing 250-300g were
used. Each animal was sacrificed by a single stun and The aqueous bark extract of E. utile
bled at the jugular vein. A piece of about 10cm long of The aqueous bark extractions obtained were
the terminal ileum was excised. The lumen was reddish-brown with a faint pleasant scent and a pH
washed out with Tyrode solution with a pipette. A 2- of 3 to 4.4. After treatment of the extract with
3cm segment was cut off and suspended in a 5ml bath activated charcoal, the recovered extract was pale
of Tyrode solution. The organ bath was maintained at yellow and had a pH of 4 ± 0.2.
350C and aerated with a constant flow of oxygen. The
lower end of the isolated tissue was attached by means
of a looped thread to a hook on the glass oxygen tube.
Effect of E. utile extract on gastric acid in the
The upper end was hooked to a force transducer Shay rats
mounted and connected to a 2-Channel “Gemini” The total amount of titratable gastric acid output
electronic recorder (Ugo Basile, Italy) to record (GAO) produced by each rat for a particular period
contractions. The tension on the tissue was 10g. Test was calculated using total volume of the clear
substances were left in contact with the tissue for thirty gastric effluents (VE) and the titre value. In Figure
seconds before being washed out three times by upward 1A, which depicts 4h ligation measurements,
displacement of bathing fluid. ranitidine significantly decreased titratable acid (p
200 Afr. J. Biomed. Res. Vol. 13, No. 3, 2010 John and Onabanjo
 Entandrophragma utile and gastric acid secretion
< 0.005). The stomach effluents of E. utile treated mean GAO values were 0.55 + 0.2, 0.53 + 0.17,
rats did not show lower acidity than controls. 0.59 + 0.13 and 1.33 + 0.6 respectively for 3, 4, 5
Figure 2 shows the relationship between GAO and and 6h ligation.
ligation period. Titratable acidity was lower than The levels of significance for the difference
controls in E. utile treated rats in the 6h ligation between controls and extract treated rats were
group (p< 0.05) and not in shorter ligation periods. p<0.05 for 3h period, p>0.05 for 4 and 5 h
Control values obtained with mean GAO were ligations and p<0.01 for 6h ligation. Chronic
0.39 + 0.1, 0.38 + 0.2, 0.61 + 0.21 and 2.82 + 0.7 administration of E. utile extract resulted in block
uEq g-1 for 3, 4, 5 and 6h ligation respectively. of gastric acid production (Figure 3) using the 4h
With the administration of E.utile extract, the ligation period.

0.6 FOUR HOURS GASTRIC ACIDITY MEASUREMENT

titratable acid micro Eq/g

A
0.5
body weight

0.4
0.3
*
0.2
0.1
0
control ranitidine extract

45 PEPTIC ACTIVITY OF FOUR HOURS GASTRIC SECRETIONS

40
mg/dL bovine serum albumin

B
35
30
25
*
20
15
10
**
5
0
control ranitidine extract
Fig. 1
Results of analysis of gastric effluents collected over 4h after ligation of rat pylori. Drugs were given orally immediately after
ligation. Gastric effluents were collected from sacrificed animals, centrifuged, and analysed for titratable acidity using phenol
red and for peptic activity by spectrophotometrical assay of peptic digestion of bovine serum albumin. Ranitidine, a clinically
effective anti-ulcer drug, significantly decreased titratable gastric acidity (p<0.005) and peptic activity of gastric effluents
(p<0.001). The E. utile extract significantly decreased peptic activity during 4h (p<0.01).

201 Afr. J. Biomed. Res. Vol. 13, No. 3, 2010 John and Onabanjo
 Entandrophragma utile and gastric acid secretion

GASTRIC ACIDITY MEASUREMENTS FOR INCREASING

LIGATION PERIODS

titratable acid micro Eq/g

4 *

body weight 3

2
Control
1
E.utile

0
3h 4h 5h 6h
ligation period
Fig. 2
Acute administration of E. utile bark extract negatively affects gastric acid secretory mechanisms. Control rats were given 1
ml saline and test rats were given 1ml of 100 mg ml-1 E. utile extract by oral cannulation immediately after ligation. Inhibition
of acid secretion was observable by the Shay rat acid titration method when the ratio secreted gastric acid/aqueous extract
content of stomachs is high (6h ligation). The significance of the difference between the controls and the extract treated
stomachs for the 6h ligation is p<0.01.

0.6 FOUR HOURS GASTRIC ACIDITY MEASUREMENT AFTER

ACUTE AND CHRONIC E. UTILE ADMINISTRATION
titratable acid micro Eq/g

0.5

0.4
body weight

0.3

0.2

0.1 *

0
control acute E. utile chronic E. utile
Fig. 3. Chronic administration of E. utile bark extract negatively affects gastric acid secretory mechanisms. The plot compares
titratable acidity of 4h gastric effluents in rats given an acute dosage of 1ml of 100 mg ml -1 extract of E. utile after ligation and
in rats that were chronically fed with 100 mg ml -1 aqueous extract of E.utile ad libitum over six weeks in their feeding bottles.
The data indicates the extract inhibitory activity takes more than 4h to effect and the extract itself, having a pH range of 3 - 4.4,
may contribute to titratable acidity of gastric effluents in the acute dosage rats. Chronic administration of E. utile extract
resulted in block of gastric acid production using the 4h ligation period.

Effect of E. utile extract on peptic activity reddish-purple instead of the bluish-purple

measurements in the Shay rats obtained in the controls. In these specimens the
The colour development after application of optical density could not be read. Figure 1B
Ohnishi and Barr procedure (1978) to effluents in shows the mean peptic activity for controls,
some of the animals treated with the extract was ranitidine, and E. utile extract treated rats,

202 Afr. J. Biomed. Res. Vol. 13, No. 3, 2010 John and Onabanjo
 Entandrophragma utile and gastric acid secretion
determined spectrophotometrically using a doses of mepyramine or the extract (Figure 5). A
standard curve (Prino et al., 1971 method). plot of response (contraction amplitude) against
Control peptic activity (mg/dL bovine serum log dose of histamine was shifted to the right by
albumin digested) was 38.75 + 4.05. The extract either mepyramine or the extract, both showing
produced a statistically significant fall in peptic histamine antagonism. Automatic linear trendlines
activity, giving PA of 14.8 + 4.67 (p<0.01) generated by Microsoft Excel 2007 are included in
comparable with ranitidine giving PA value of 3.4 Figure 5 and show that mepyramine gave a parallel
+ 0.72 (p<0.001). shift of the histamine dose-response curve typical
of a competitive antagonism. Similarly the extract
Effects of E.utile extract on gastrointestinal graph trendline indicated a non-parallel shift with a
muscle histamine receptors lowering of maximal response typical of a non-
The aqueous bark extract of E.utile did not competitive antagonism (Figure 5).
produce contraction or relaxation of the guinea-pig
ileum when given with increasing doses of 2-10 x
10-3 g and observed with alternate doses of DISCUSSION
histamine (1-10-ug) that contracted the ileum in a
dose-dependent manner. In the three point assay In the 4h ligation rats the mean titratable gastric
of (the extract of) E.utile against constant acidity was 0.38 uEq g-1 as compared to the
submaximal contractions induced by 10ug controls of 0.53 uEq g-1, the extract seeming not to
histamine, the extract of E.utile produced an have any antisecretory effect. Because the pH of
antihistaminergic effect. In the latter study using the extract (3 – 4.4) was in the acid range, we
atropinized bathing solution, E.utile given in doses thought that the ratio of extract: to gastric
of 10 -160 x 10-3 g antagonized 10 ug histamine- secretions might be important to be able to observe
induced contractions by 28-62% in a dose- any antisecretory effect. Therefore we used
dependent manner (Figure 4). Mepyramine, but not increasing ligation periods. The extract
ranitidine, also antagonized the contractile effect significantly decreased titratable acidity of gastric
of histamine. Histamine gave a graded dose- effluents for the 6h ligation period, p<0.01 (Figure
response relationship (Figure 5), which was also 2).
established respectively in the presence of constant

1 min

Figure 4.
E utile bark extract antagonizes histaminergic contractions of the guinea-pig ileum in a dose-dependent manner. The ileum was
bathed with atropinized Tyrode solution. The agonist, 10 ug histamine, which produced a large submaximal response was used
against increasing doses of the extract added to the organ bath 30s before histamine. E.utile antagonized histamine-induced
contractions in a dose-dependent manner.

203 Afr. J. Biomed. Res. Vol. 13, No. 3, 2010 John and Onabanjo
 Entandrophragma utile and gastric acid secretion

Figure 5.
E utile bark extract antagonizes histaminergic contractions of the guinea-pig ileum non-competitively.
The data are from tissue mounted in atropinized Tyrode solution. Contractile responses of the ileum were
obtained for increasing doses of histamine. The responses to the same increasing doses of histamine were
repeated in the presence of a constant dose of 5 x 10-6 M mepyramine or a constant dose of 10 x 10-3 g E.
utile extract. Linear trend lines were automatically generated by Microsoft Excel 2007. Mepyramine
gave a parallel shift of the histamine dose-response graph to the right typical of a competitive antagonism.
E. utile extract gave a non-parallel shift to the right with a lowering of maximal response typical of a non-
competitive antagonism.

204 Afr. J. Biomed. Res. Vol. 13, No. 3, 2010 John and Onabanjo
 Entandrophragma utile and gastric acid secretion

This corresponds with the observed decreased in gut. In a different study of the antisecretory effect
peptic activity produced by the extract even with of the aqueous extract of E. utile using the Ghosh
4h ligation. It may appear that the peptic activity and Schild rat preparation, we observed that the
inhibitory effect of the extract is more immediate extract may be also acting on proton pumps in the
(within 4h) than the acid secretion inhibitory effect gastric mucosa. Because of the plurality of
of the extract (within 6 h). However in a different mechanisms that may be affected by the extract –
study of the antisecretory effect of E. utile using a histamine H1, histamine H2, and the proton pump -
continuous perfusion method, gastric acidity began in the gastric mucosa, we need to investigate the
to fall within 5 min of initiation of extract infusion molecular mechanisms involved, particularly the
(John 1994). In the present report, when the second messenger systems and how they are linked
extract was administered chronically before the at receptor levels. The present documentation
measurement of gastric acid output, the 4h ligation indicates that the aqueous bark extract of E. utile
gastric effluent collection showed an inhibitory could be further studied for its usefulness in
effect of the extract on titratable acid secretion controlling gastric acid secretion.
(Figure 3) possibly because the ratio (secreted
gastric acid/aqueous extract content) was higher Conclusion
than for the acute studies. The mean 4h Short term administration of effective doses of
-1 +
measurements fell to 0.25 uEq g H after 6 weeks E.utile extract decreases gastric secretion of acid
which indicates that the extract disturbed the and also decreases gastric peptic activity. Long
function of the secretory mechanism during term administration of E. utile extract appears to
chronic intake. The biochemical assay for peptic negatively affect the mechanisms involved in
activity by Ohnishi and Barr procedure (1978) was gastric acid secretion. One mechanism by which
not compatible with the E. utile extract therefore the components of the E. utile bark extract produce
we have used the data from the Prino et al. (1971) anti-ulcer effect appears to be by antagonism of
method. There was a statistically significant histamine receptors. The two properties of the E.
decrease in peptic activity for acute E. utile utile extract on acid and pepsin may be valuable
administration prior to 4 h ligation gastric effluent for patients with compromised mucosa due to
collections even when the data did not show aspirin ingestion (Ivey, 1988) or other related
decreased titratable acid secretion. The data conditions. E. utile bark extract is a potential
indicates that E. utile showed antisecretory adjunct therapy that can minimize aggravation of
properties for both acidity and peptic activity. The mucosal damage by acid-peptic autodigestion.
effect on acid secretion might have been masked
for short ligation periods because the extract itself Acknowlegdements
has a low pH in the acid range. The extract did not The authors acknowledge with thanks that much of this work
was done in the Chemotherapy Unit of the Department of
show intrinsic activity on the guinea-pig ileum but Pharmacology, College of Medicine of the University of
antagonized the contractile effect of histamine in a Lagos, Idi-Araba, Lagos, Nigeria, under the supervision of
dose dependent manner. Compared to mepyramine Prof. A. O. Onabanjo. The authors also thank Chief E. O.
antagonism of histamine, the effect of the extract Esho, a traditional medicine practitioner, who introduced the
was not competitive antagonism and may not be E. utile bark and its medicinal properties to us. The authors
also extend much gratitude to taxonomist, Dr. M. O.
directly at the H1-histamine receptor. In the gut, Soladoye, of the Forestry Research Institute of Nigeria,
contraction is mediated through H1-receptor Ibadan who assisted us with the botanical profile of the
agonists and acid secretion is mediated through Entandrophragma utile tree.
H2-receptor agonists (Dale and Laidlaw, 1910;
1911; Black et al., 1972), therefore, the extract
may be blocking both types of histamine receptors REFERENCES
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