Journal of Ethnopharmacology, 29 (1990) 25 34 25

Elsevier Scientific Publishers Ireland Ltd.

EVALUATION OF TURMERIC (CURCUMA LONGA) FOR GASTRIC

AND DUODENAL ANTIULCER ACTIVITY IN RATS

S. RAFATULLAH, M. TARIQ, M.A. AL-YAHYA, J.S. MOSSA and A.M. AGEEL

Medicinal, Aromatic and Poisonous Plants Research Center and Departments of Pharmacology
and Pharmacognosy, College of Pharmacy, King Saud University, P.O. Box 2b57, Riyadh-1H51
(Saudi Arabia)

(Accepted October 18,1989)

Summary

An ethanol extract of turmeric was studied in rats for its ability to

inhibit gastric secretion and to protect gastroduodenal mucosa against the
injuries caused by pyloric ligation, hypothermic-restraint stress, indometha-
cin, reserpine and cysteamine administration and cystodestructive agents
including 80% ethanol, 0.6 M HC1, 0.2 M NaOH and 25% NaCl. An oral dose
of 500 mg/kg of the extract produced significant anti-ulcerogenic activity in
rats subjected to hypothermic-restraint stress, pyloruic ligation and indome-
thacin and reserpine administration. The extract had a highly significant
protective effect against cystodestructive agents. The reduction in the inten-
sity of ulceration of cysteamine-induced duodenal ulcers was not found to be
statistically significant. Turmeric extract not only increased the gastric wall
mucus significantly but also restored the non-protein sulfhydryl (NP-SH) con-
tent in the glandular stomachs of the rats.

Introduction

Upper gastrointestinal bleeding can be a life-threatening complication in

patients with gastric mucosal injury (Smith and Kvietys, 1988). In the recent
years a wide-spread search has been launched to identify new anti-ulcer
drugs from synthetic and natural resources. A large number of dietary
nutrients, spices and condiments, namely banana (Best et al., 1984), ginger
(Al-Yahya et al., 1989), cinnamon (Akira et al., 1986), a-tocopherol (Tariq,
1988) and selenium (Parmar et al., 1988) have been shown to possess signifi-
cant antisecretory and gastroprotective activity. Although the modes of
action of these agents are far from clear, substances like a-tocopherol and

Correspondence to: M. Tariq.

0378-8741/$03.85 1990 Elsevier Scientific Publishers Ireland Ltd.

Published and Printed in Ireland
26

selenium have been claimed to protect gastric mucosa by scavenging free

radicals (Tariq, 1988; Szabo, 1989).
Many plants are known to possess ingredients with antioxidative
properties. Tanizawa et al. (1984) have isolated antioxidative compounds
from green tea leaves. A potent antioxidative compound was also isolated by
Toda et al. (1985a) from Plantago asiatica. Tariq and Al-Yahya (1983) have
reported an a-tocopherol rich fraction isolated from date palm seeds, which
was found to have significant activity against endotoxin-induced myocardial
damage.
Turmeric, Curcuma longa L. (Zingiberaceae), is widely used in the tradi-
tional medicine of various countries of the world for the treatment of rheu-
matism and inflammatory and ulcerative conditions (Mehra et al., 1984,
Ageel et al., 1987). Curcuma longa rhizomes have been reported to possess
anti-oxidative activity (Toda et al., 1985b). Although much work has been
done on turmeric and its compounds in relation to rheumatism and its
reputed antihepatotoxic action (Kiso et al., 1983), there are no data available
regarding its gastric anti-ulcer potential. Therefore, the present study was
undertaken to evaluate an ethanol extract of turmeric for its gastric and
duodenal anti-ulcer activity.

Materials and methods

Animals
Inbred Wistar albino rats of either sex of approximately the same age,
weighing between 200 230 g, were obtained from the Experimental Animal
Care Center, College of Pharmacy, King Saud University, Riyadh. The rats
were fed standard chow diet (Silos and Flour Mills Organization Feed Mill,
Riyad) and water ad libitum. They were divided into various groups of six to
eight animals each. The distribution of the animals into groups, the sequence
of the trials and the treatment allotted to each group were randomized.

Extract preparation
Turmeric rhizomes were procured from the local market of Riyadh, Saudi
Arabia and identified in the Taxonomy Division of the Medicinal, Aromatic
and Poisonous Plants Research Center of King Saud University, Riyadh. The
powdered drug (500 g) was extracted using a percolation method and 96%
ethanol. The solvent was then removed at low temperature under reduced
pressure and the extracts so prepared were stored in a refrigerator for
pharmacological studies. The extract yield was 9.5% (w/w) in terms of start-
ing material. All doses are expressed here in terms of the extract itself.

Experimental gastric lesions

Unless specified otherwise, the animals were taken off food for 36 h with
access to water ad libitum before subjecting them to one of the following
procedures.
 27

Pyloric ligation. The pylorus was ligated according to the method of Shay
et al. (1945) under light ether anaesthesia with care taken not to cause bleed-
ing or to occlude blood vessels. Six hours after ligation, the animals were
killed by an overdose of ether, the stomachs removed, contents collected,
measured for volume, centrifuged and subjected to analysis for titratable
acidity against 0.1 N NaOH to pH 8 using a pH meter. Total acid output was
calculated. Each stomach was examined for lesions in the forestomach por-
tion and indexed according to severity.
Hypothermic-restraint stress-induced ulcers. The method of Levine (1971)
was followed with slight modification. The animals were taken off food for 24
h with access to water ad libitum and 1 h after receiving the corresponding
treatments, they were placed in a metallic restraint cage inside a
refrigerator (24C) for 2 h. They were killed at the end of this period.
Indomethacin-induced ulcers. Ulcers were induced according to the
method of Bhargava et al. (1973). Indomethacin was suspended in 1% carbox-
ymethycellulose in water and administered orally at a dose of 30 mg/kg (5
ml/kg). Six hours after indomethacin administration, the animals were killed.
Reserpine-induced ulcers. The method of Gupta et al. (1974) was followed.
Reserpine (CIBA) was administered in a dose of 5 mg/kg i.m. (5 ml/kg) and
the animals were killed 24 h later.
Cytoprotection studies. The method of Robert (1979) was followed. The
following necrotizing agents were administered orally to male rats in a vol-
ume of 1 ml: 80% ethanol, 0.6 M HC1, 25% NaCl and 0.2 M NaOH. Turmeric
extract (500 mg/kg; 5 ml/kg) or the vehicle alone (normal saline) was given
i.g., 30 min before the necrotizing agents. One hour after the administration
of necrotizing agents, the animals were sacrificed and each was examined for
gastric lesions.

Experimental duodenal lesions

The method described by Szabo (1978) was followed. Female wistar rats,
weighing 180 200 g were used. Food and water were available ad libitum
throughout the study. Duodenal ulcers were induced by two oral administra-
tions of cysteamine hydrochloride (300 mg/kg, p.o.) in aqueous solution (5 ml/
kg) with an interval of 4 h. All the animals were killed 48 h after the first
dose of cysteamine.

Gastric wall mucus determination

Gastric wall mucus was determined according to the modified procedure
of Come et< al. (1974). The glandular segments from stomachs which had been
opened along their greater curvature were removed and weighed. Each
segment was transferred immediately to 10 ml of 0.1% w/v Alcian blue solu-
tion (in 0.16 M sucrose solution, buffered with 0.05 M sodium acetate pH 5).
After immersion for 2 h, excess dye was removed by two successive rinses
with 10 ml of 0.25 M sucrose, first for 15 and then for 45 min. Dye complexed
with the gastric wall mucus was extracted with 10 ml of 0.5 M magnesium
28

chloride by shaking intermittently for 1 min at 30 min intervals for 2 h. Four

millilitres of blue extract were then shaken vigorously with an equal volume
of diethyl ether. The resulting emulsion was centrifuged at 3600 rev./min for
10 min and the absorbance of the aqueous layer was recorded at 580 nm. The
quantity of Alcian blue extracted per gram of net glandular tissue was then
calculated.

Estimation of non-protein sulfhydryl groups (NP-SH)

The animals were fasted for 36 h before the oral administration of 500 mg/
kg turmeric extract (5 ml/kg). Thirty minutes later, the rats were treated
with 80% ethanol. One hour after the ethanol, the animals were killed and
their stomachs removed. Gastric mucosal NP-SH was measured according to
the method of Sedlak and Lindsay (1968). The glandular stomach was
removed and homogenized in ice-cold 0.02 M EDTA. Aliquots of 5.0 ml of the
homogenates were mixed in 15-ml test tubes with 4.0 ml of distilled water
and 1.0 ml of 50% trichloroacetic acid. The tubes were shaken intermittently
for 10 15 min and centrifuged at 3000 X g. Two millilitres of supernatants
were mixed with 4.0 ml of 0.4 M Tris buffer (pH 8.9), 0.1 ml of 5,5'-dithiobis-
(2-nitrobenzoic acid) (DTNB) was added and the sample shaken. The absorb-
ance was read within 5 min of addition of DTNB at 412 nm against a reagent
blank with no homogenate.

General procedures
The ethanol extract of turmeric (100 mg/ml) was given at a dose of 500
mg/kg p.o. 30 min before the administration of an ulcerogenic agent (twice in
case of reserpine and cysteamine) and at the beginning of stress procedures.
In Shay rats it was administered immediately after pylorus ligation. Control
animals received an equivalent volume (5 ml/kg) of the normal saline vehicle.
The animals were killed at the end of specified periods using anaesthetic
ether and the stomach and duodenum were excised. The duodenum was
opened along its anti-mesenteric side and the stomach along the greater cur-
vature, their contents were rinsed off with saline and the linings examined
with a 6.4 X binocular magnifier. Lesions were assessed by two observers
unaware of the experimental protocols.
Gastric lesions induced by all the procedures used in this study were mul-
tiple in each stomach. They were evaluated singly according to their dimen-
sions and severity, and scored using a scale of 0 (no visible ulcers) to 10 (deep
lesions with a diameter greater than 8 mm in each stomach). The scores for
each single lesion were then summed so that the total score per stomach
could exceed the value of 10 (Tariq et al., 1985).
The duodenal ulcers were scored for intensity, using a scale of 0 to 3,
where 0 = no ulcer, 1 = superficial mucosal erosion, 2 = deep ulcer or
transmural necrosis, 3 = perforated or penetrated (into the pancreas or
liver) ulcer (Szabo, 1978). The ulcer index is the sum of the arithmetic mean
of the intensity for a group and the ratio of positive/total multiplied by 2,
e.g. 2.1 + (9/10 X 2).
 29

The results refer to the average lesion score S.E.M. Statistical analysis
of the severity of gastric ulcers was done by Student's t-test.

Results

As shown in Table 1, pyloric ligation induced ulcers and turmeric extract

led to a significant decrease in the ulcer index and total acidity of the stom-
ach contents at the end of the 6 h period. The ulcers were mainly in the
forestomach and few haemorrhagic spots were found in the glandular stom-
ach. Administration of indomethacin or reserpine, and subjecting the animals
to cold and restraint resulted in the production of gastric mucosal damage
mainly in the glandular segment of the stomachs. The majority of these
lesions were gastric erosions. Pretreatment with turmeric extract adminis-
tered orally was effective in reducing the intensity of ulceration in indome-
thacin, reserpine and restraint stressed groups (Table 2). Lowered gastric
wall mucus was observed in the animals subjected to hypothermic-restraint
stress, but this could be reversed by treatment with turmeric extract (Table
3).
Lesions induced by the various necrotizing agents were grouped in
varying sized patches, usually parallel to the major axis of the stomach.
Treatment with turmeric extract significantly reduced the severity of these
lesions (Table 4).
Administration of duodenal ulcerogen cysteamine hydrochloride caused
mortality in 12.5% of the rats in 24 h. Rats which died had perforated duo-
denal ulcers. Cysteamine treatment produced duodenal ulcers in 90% of all
the rats. Usually two ulcers were produced close to the pylorus, the larger
on the anterior and the smaller on the posterior wall of the duodenum. They
were elongated, extending longitudinally down the duodenum and could eas-
ily be measured. Turmeric treatment reduced the average lesion score, but
this change was statistically not significant (Table 2).

TABLE 1

EFFECT OF AN ETHANOL EXTRACT OF TURMERIC ON THE VOLUME OF GASTRIC

SECRETIONS, ACIDITY AND THE DEGREE OF ULCERATION IN 6-H PYLORUS
LIGATED (SHAY) RATS

Treatment N Dose Mean S.E.M.

(mg/kg,
i.p.) Volume of Titratable Total acid Ulcer
gastric acidity output index
secretion (mEq/1)
(ml)

Control 6 8.66 0.72 70.0 2.7 606 52 1.00 0.36

Turmeric 6 500 4.58 1.01* 43.9 8.0* 229 72** 0.33 0.21**

Significance relative to control data: *P < 0.05, **P < 0.01.

30

TABLE 2

EFFECT OF AN ETHANOL EXTRACT OF TURMERIC ON EXPERIMENTALLY-INDUCED

GASTRIC AND DUODENAL ULCERS IN RATS

Treatment N Oral dose Lesion score

(mg/kg) (Mean S.E.M.)

Hypothermic-restraint stress
Control 6 26.5 2.3
Turmeric 6 500 X 1 17.2 + 2.4*
Indomethacin
Control 6 35.2 1.6
Turmeric 6 500 X 1 23.3 3.1***
Reserpine
Control 6 37.0 2.0
Turmeric 6 500 X 2 18.0 3.1***
Cysteamine
Control 7 1.85 0.26
Turmeric 7 500 X 2 1.00 0.37

Significance relative to respective control data: *P < 0.05, **P < 0.01. ***P < 0.001.

TABLE 3

MEAN (S.E.M.) EFFECT OF ETHANOLIC EXTRACT OF TURMERIC ON GASTRIC

W A L L MUCUS IN RATS WITH HYPOTHERMIC-RESISTANT STRESS

Group N Oral Gastric wall mucus P

dose ing Alcian blue/g wet
(mg/kg) glandular tissue)

Normal 7
_ 305 24* < 0.001
(unstressed)
Control 7 196 9
(stressed)
Turmeric 7 500 385 31* < 0.001
(stressed)

TABLE 4

EFFECT OF AN ETHANOL EXTRACT OF TURMERMIC ON THE GASTRIC LESIONS

INDUCED BY VARIOUS NECROTIZING AGENTS

Procedure N Ulcer index (mean S.E.M.)

Control Turmeric 500 mg/kg, p.o.

80% Ethanol 6 6.83 + 0.40 4.00 0.40*

0.6 M HC1 6 6.83 0.79 1.50 0.50*
25% NaCl 6 6.50 + 0.76 1.66 0.42*
0.2 M NaOH 6 6.55 0.80 2.00 0.36*

Significance relative to respective controls: *P < 0.001.

 31

TABLE 5

MEAN ( S.E.M.) EFFECT OF AN ETHANOL EXTRACT OF TURMERIC ON NON-PRO-

TEIN SULFHYDRYL CONTENT IN THE GLANDULAR STOMACHS OF RATS TREATED
WITH 80% ETHANOL

Treatment N Oral dose Non-protein sulfhydryl content

(mg/kg) (/imol/g of tissue)

Normal 7 3.15 0.18*

Turmeric 7 500 2.89 0.23*
80% Ethanol 7 1.42 0.06*
(1.0 ml)
Turmeric + 80% 6 500 2.27 0.12*
ethanol
(1.0 ml)

The gastric mucosal NP-SH content was significantly decreased following

the administration of 80% ethanol. Treatment with the turmeric extract sig-
nificantly prevented this reduction (Table 5).

Discussion

The results of this study clearly indicate that the oral administration of an
ethanol extract of turmeric produced significant anti-ulcer and cytoprotec-
tive effects in rats. Hypothermic-restraint stress ulcers have been widely
used experimentally for the evaluation of anti-ulcer activity in rats because
of data reproducibility (Murakami et al., 1985). Disturbances of gastric
mucosal microcirculation (Guth, 1972), alteration of gastric secretion (Kita-
gawa et al., 1979) and abnormal gastric motility (Watanabe, 1966) have been
considered to be the pathogenic mechanisms responsible for stress-induced
gastric mucosal lesions and gastric mucus depletion (Koo et al., 1986). The
increase in gastric acid secretion is considered to be an important factor in
the genesis of stress ulcer and is often termed as the "aggressive factor"
(Goa and Monk, 1987). The antisecretory activity of turmeric as observed in
our Shay rat model might be important in protecting gastric mucosa against
stress-induced ulceration.
Turmeric has been shown to possess highly significant antioxidant activity
and Toda et al. (1985b) have shown that the methanol extract of turmeric
possesses better anti-oxidant properties than a-tocopherol. Young et al.
(1976) found that a-tocopherol can mitigate stress-induced ischemia in tissues.
Our findings are in agreement with earlier authors who reported significant
anti-ulcer activity for a number of other anti-oxidants including superoxide
dimutase, vitamin E, selenium and AT-acetylcysteine (Javor et al., 1986; Par-
mar et al., 1988; Tariq, 1988). The ability of turmeric extract to produce a
significant reduction of the gastric mucosal damage induced by indomethacin
32

and reserpine further confirms its potent anti-ulcer activity. Of these,

indomethacin is a potent prostaglandin biosynthesis inhibitor (Whittle, 1981).
There is mounting evidence that an increase of certain endogenous
prostaglandins can enhance gastric mucosal resistance against ulcerogenic
agents (Konturek et al., 1984; Wallace and Whittle, 1985). Many of these anti-
oxidants have been shown to stimulate the synthesis of prostaglandins by
inhibiting lipoxygenase (Gwebu et al., 1980; Sok et al., 1980; Reinton et al.,
1981).
The severity of duodenal ulcers, though reduced, was not statistically sig-
nificant after oral pretreatment with turmeric extract. Cysteamine-induced
duodenal ulcers are considered to be due to a long-lasting hypersecretion of
gastric acid (Szabo et al., 1977; Kirkegaard et al., 1980). It is possible that
higher and more frequent dosing with turmeric extract might reveal some
duodenal anti-ulcer activity in this experimental model. Even the standard
H receptor antagonist cimetidine has been found to be less effective in rats
2

against cysteamine-induced duodenal ulceration (Szabo et al., 1979).

Turmeric extract significantly protected gastric mucosa againts several
known necrotizing agents, namely 80% ethanol, 0.6 M HC1, 0.2 M NaOH and
25% NaCl. These results support the findings of Kiso et al. (1983), who
reported a protective effect of turmeric against carbon tetrachloride-induced
hepatocellular injury. The extract also inhibited ethanol-induced depletion of
the non-protein sulfhydryl (NP-SH) content of the glandular mucosa of the
stomach. Glutathione (GSH) has been reported to play an important role in
the process of cellular injury (Robert et al., 1983). Szabo et al. (1981) found a
significant decrease in NP-SH following necrotizing agents in ulcerative
doses; therefore, the replenishment of sulfhydryl levels in gastric mucosa by
turmeric extract may contribute to its anti-ulcer activity.
Our findings show that the ethanolic extract of turmeric has significant
anti-ulcer, antisecretory and cytoprotective activity in rats.

Acknowledgement

The authors are thankful to the King Abdulaziz City for Science and Tech-
nology (KACST) for financial support.

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