Pharmaceutical Biology

ISSN: 1388-0209 (Print) 1744-5116 (Online) Journal homepage: http://www.tandfonline.com/loi/iphb20

Anti-gastric Ulcer and Cytoprotective Properties of

Caralluma arabica

M.N.M. Zakaria, M.W. Islam, R. Radhakrishnan, X.M. Liu, A. Ismail, M. Kamil,

K. Chan & A. Al-Attas

To cite this article: M.N.M. Zakaria, M.W. Islam, R. Radhakrishnan, X.M. Liu, A. Ismail, M. Kamil,
K. Chan & A. Al-Attas (2002) Anti-gastric Ulcer and Cytoprotective Properties of Caralluma arabica,
Pharmaceutical Biology, 40:3, 225-230, DOI: 10.1076/phbi.40.3.225.5830

To link to this article: https://doi.org/10.1076/phbi.40.3.225.5830

Published online: 29 Sep 2008.

Submit your article to this journal

Article views: 23

Citing articles: 7 View citing articles

Full Terms & Conditions of access and use can be found at

http://www.tandfonline.com/action/journalInformation?journalCode=iphb20
 Pharmaceutical Biology
2002, Vol. 40, No. 03, pp. 225–230
Anti-gastric Ulcer and Cytoprotective Properties of
Caralluma arabica
M.N.M. Zakaria*, M.W. Islam, R. Radhakrishnan, X.M. Liu, A. Ismail, M. Kamil1, K. Chan and A. Al-Attas
Department of Pharmacology & Toxicology and 1Department of Pharmacognostic Sciences, Zayed Complex of Herbal
Research & Traditional Medicine (ZCHRTM), Ministry of Health, Post Box 29300, Abu Dhabi, United Arab Emirates
Abstract
In the present study, a 10% ethanolic extract of Caralluma
arabica, at the doses of 200 and 400 mg/kg, was evaluated
for the antigastric ulcer activity using experimental gastric
ulcer models induced by phenylbutazone or indomethacin
and 80% ethanol or 0.2 N NaOH, and cold restraint stress.
Some experiments were carried out to study the effects of C.
arabica extract on gastric acid secretion in pyloric ligation-
induced ulcer and gastric wall mucin production. The 10%
ethanolic extract of C. arabica produced a dose-dependent
reduction in all experimentally induced gastric lesions used
in the present study. The cytoprotective activity of C. arabica
in ethanol-induced ulcer was completely abolished by pre-
treatment with indomethacin. Induction of gastric ulcer
reduced gastric wall production of mucin to 50.8% of its
initial value. This reduction was completely prevented by
pretreatment with C. arabica extract. C. arabica extract sig-
nificantly reduced total gastric acidity (from 22.4 ± 1.5 to 9.2
± 1.6 mEq/L) and volume of gastric secretions (from 9.98 ±
0.7 to 2.03 ± 0.2 ml). Results of the present study reveal that
the C. arabica extract protects gastric mucosal cells against
experimental gastric mucosal damage. This effect confirms
results of other studies on Caralluma species and seems
to be mediated by multi-mechanisms including increased
gastric production of prostaglandins and mucin and reduced
gastric acidity.
Keywords: Caralluma arabica, gastric ulcer, cytoprotective,
mucin, gastric acidity.
Introduction
Caralluma arabica (Asclepeadaceae) is a well known plant
commonly used in traditional medicine in the United Arab
Accepted: January 16, 2002
*Address correspondence to: M.N.M. Zakaria, Zayed Complex for Herbal Research & Traditional Medicine, Ministry of Health, Post Box
29300, Abu Dhabi, United Arab Emirates, Fax: +9712-5826919
1388-0209/02/4003-225$16.00
© Swets & Zeitlinger
Emirates for the treatment of different disease conditions.
Some species of Caralluma are used in folk medicine as
antipyretic, antirheumatic and reported to possess significant
anti-inflammatory activity (Ahmad et al., 1993). The present
study was carried out to assess the possible anti-gastric ulcer
and cytoprotective properties of Caralluma arabica, widely
growing in the United Arab Emirates, to confirm and extend
its uses in traditional medicine.
Materials and methods
Animals
Wistar or Sprague-Dawley rats weighing 200–250 g of either
sex, purchased from Harlan, UK and bred in the Life Science
Support unit of ZCHRTM were used in the present investi-
gation. Animals were maintained under standard environ-
mental conditions and had access to food and water ad
libitum. During fasting (40 h before the experiment), rats had
free access to water and caprophagy was avoided by keeping
rats in cages with mesh wire bottom.
Preparation of the extract
The plant was collected from the UAE and authenticated by
the taxonomy unit. Aerial parts of the plant were dried under
shade, powdered and exhaustively extracted with 10%
ethanol. The extract was evaporated under vacuum using a
Bucchi rotary evaporator until dried. The dried extract was
authenticated and standardized using TLC and HPLC before
it was supplied for the pharmacological studies. The dried
extract was dispersed in distilled water for administration to
animals.
226 M.N.M. Zakaria et al.
Chemicals
Phenylbutazone (Sigma), indomethacin (Winlab), ethanol
(BDH), sodium hydroxide (Merck) and Alcian blue
(Gainland Chem. Company) were used in the present study.
Evaluation of antigastric ulcer properties
The volume of the extract given to each rat was 1 ml/100 g
body weight in all the experiments.
Experimental gastric ulcer induced by nonsteroidal
anti-inflammatory or necrotizing agents
The C. arabica extract (200 and 400 mg/kg, p.o.,) was given
1 h before induction of gastric ulcer. One hour later, a single
oral dose of the nonsteroidal anti-inflammatory drugs
indomethacin (30 mg/kg) and phenylbutazone (200 mg/kg)
suspended in carboxymethylcellulose (0.5% w/w) were used
to induce gastric ulcer in 40 h fasting rats (Bhargava et al.,
1973; Galil & Marshal, 1968). A single oral dose of the
necrotizing agents, ethanol (0.5 ml of 80% solution) or
sodium hydroxide (0.5 ml of 0.2 M solution) was used to
induce gastric lesions in 40 h fasting rats in the present study
(Robert et al., 1979). Six hours after administration of non-
steroidal anti-inflammatory drugs or one hour after giving
necrotizing agents, rats were sacrificed using an overdose
of ether, stomachs were removed and opened along the
greater curvature, rinsed with saline and pinned flat on a cork
board. Stomachs were examined for ulcers by two different
observers unaware of the experimental protocol using an
illuminator (3¥) according to the severity scale (ulcer score)
described by Galil and Marshal (1968). Results obtained
from treated groups were compared with those of control
group which received only the vehicle. Mean ulcer scores for
a group of rats were calculated and expressed as an ulcer
index. Inhibition of ulcer was calculated as (ulcer index of
control group – ulcer index of treated group) ¥ 100/ulcer
index of control group.
Gastric ulcer induced by pylorus ligation
Effects on gastric lesion and secretions were carried out by
ligation of the pyloric end of the stomach by silk suture
according to the method described by Shay et al. (1945). The
C. arabica extract (400 mg/kg) or vehicle was given intra-
gastrically immediately after pylorus ligation. Six hours later,
the animals were killed by cervical dislocation, stomachs
were removed and the gastric contents were collected, cen-
trifuged, total volume was measured and titrated for acidity
against 0.1 N NaOH using Radiometer automatic titration
unit (Titra Lab, Copenhagen). The acidity of gastric contents
was determined in milliequivalents per liter (mEq/L) and the
total acid output was calculated (liquid volume ¥ acidity).
Stomachs were examined and evaluated for severity of
ulcers.
Gastric ulcer induced by hypothermic restraint stress
Hypothermic restraint stress ulcer was induced in 36 h fasting
rats, 1 h after administration of C. arabica extract or vehicle
according to the method of Leveine (1971). Animals were
kept immobilized in restrained cages in cold room main-
tained at +4 °C for 2 h and killed with an overdose of ether.
Stomachs were excised and examined for the severity of
intraluminal bleeding according to the arbitrary scale
described by Chiu et al. (1984).
Determination of gastric wall mucin content
Gastric wall content of mucin was determined in normal rats
as well as hypothermic restraint stress ulcer induced in
control and treated groups according to the method described
by Corne et al. (1974). The glandular part of each stomach
(0.5 g) was placed 10 ml of 1% Alcian blue solution in
0.16 M sodium acetate (pH 5.8) for 2 h. The dye complex was
extracted with 0.5 M magnesium chloride solution, cen-
trifuged and measured spectrophotometrically at 580 nm
using a standard curve of Alcian blue.
Modulation of prostaglandin in indomethacin
pretreated rats
Indomethacin (5 mg/kg, s.c.) was given to fasting rats 1 h
before C. arabica extract or the vehicle. One hour later, the
necrotizing agent, ethanol (0.5 ml of 80% solution), was
given, and severity of ulcer was evaluated as described above.
Statistical analysis
The results are presented as mean ± S.E.M. Student’s t-test
was used to test the significance of the difference between
treated and control groups at P < 0.05.
Results
Effect on nonsteroidal anti-inflammatory
agents-induced ulcer
Acute oral administration of 10% ethanolic extract of C.
arabica at doses of 200 and 400 mg/kg significantly reduced
the index of gastric ulcer induced by phenylbutazone. C.
arabica extract at the two dose levels used significantly inhib-
ited the gastric mucosal damage induced by phenylbutazone
by about 80% (Table 1). Acute oral treatment with C. arabica
extract at doses of 200 and 400 mg/kg significantly reduced
the index of indomethacin-induced gastric ulcer in a dose
dependent manner. Doses of 200 and 400 mg/kg inhibited the
indomethacin-induced mucosal lesions by 50.1 and 77.4%,
respectively.
Effect on necrotizing agents-induced ulcers
As shown in Table 2, acute oral administration of C. arabica
extract at the dose of 400 mg/kg significantly inhibited the
 Anti-ulcer and cytoprotective properties of Caralluma arabica 227

Table 1. Antigastric ulcer activity of Caralluma arabica (200 and 400 mg/kg, p.o.) versus
phenylbutazone and indomethacin-induced gastric ulcer.

Incidence

Absolute Ulcer Percentage of

value Percent index inhibition

Phenylbutazone:
Control 9/9 100.0 3.44 ± 0.175 0.00
Caralluma arabica 4/6 66.7 0.67 ± 0.21* 80.50
200 mg/kg, p.o.
Caralluma arabica 3/6 50.0 0.67 ± 0.33* 80.50
400 mg/kg, p.o.
Indomethacin:
Control 12/12 100.0 3.67 ± 0.14 0.00
Caralluma arabica 5/6 83.3 1.83 ± 0.54* 50.10
200 mg/kg, p.o.
Caralluma arabica 4/6 66.7 0.83 ± 0.31* 77.40
400 mg/kg, p.o.

* Significantly different from control value at P < 0.05.

Table 2. Antigastric ulcer activity of Caralluma arabica (200 and 400 mg/kg, p.o.) versus
ethanol and NaOH-induced gastric ulcer.

Incidence

Absolute Ulcer Percentage of

value Percent Index inhibition

Ethanol:
Control 8/8 100.0 3.88 ± 0.125 0.00
Caralluma arabica 6/6 100.0 3.50 ± 0.22 9.80
200 mg/kg, p.o.
Caralluma arabica 4/6 66.7 1.33 ± 0.56* 65.70
400 mg/kg, p.o.
NaOH:
Control 6/6 100.0 3.83 ± 0.17 0.00
Caralluma arabica 5/6 88.3 1.33 ± 0.33* 65.30
200 mg/kg, p.o.
Caralluma arabica 5/6 88.3 1.17 ± 0.31* 69.50
400 mg/kg, p.o.

* Significantly different from control value at P < 0.05.

index of gastric mucosal damage and showed 65.7% protec- Effect on cold restraint stress ulcer
tion against ethanol-induced gastric ulcer. The low dose of
Acute treatment with C. arabica extract at a dose of
C. arabica extract did not show a significant effect on
400 mg/kg significantly inhibited gastric mucosal damage
severity of ethanol-induced gastric mucosal damage. This
induced by cold restraint stress by 50% compared with the
cytoprotective effect produced by C. arabica extract was
control group (Table 3).
completely abolished by pretreatment with indomethacin.
Treatment with 10% ethanolic extract of C. arabica at the
doses of 200 and 400 mg/kg significantly reduced the index
Effect on pyloric ligation-induced gastric ulcer
of gastric ulceration induced by sodium hydroxide and
showed protection against NaOH-induced gastric ulcer by As presented in Table 3, acute oral treatment with C. arabica
65.3 and 69.5%, respectively. extract at a dose of 400 mg/kg markedly protected the gastric
228 M.N.M. Zakaria et al.

Table 3. Antigastric ulcer activity of Caralluma arabica (400 mg/kg, p.o.) versus cold
restraint stress and pyloric ligation-induced gastric ulcer.

Incidence

Absolute Ulcer Percentage of

value Percent index inhibition

Cold restraint stress

Control 10/10 100.0 3.20 ± 0.22 0.00
Caralluma arabica 10/10 100.0 1.60 ± 0.22* 50.00
400 mg/kg, p.o.
Pyloric ligation
Control 10/10 100.0 2.50 ± 0.22 0.00
Caralluma arabica 2/8 25.0 0.25 ± 0.16* 90.00
400 mg/kg, p.o.

* Significantly different from control value at P < 0.05.

Table 4. Effect of indomethacin treatment (5 mg/kg, s.c.) on antigastric ulcer activity of

Caralluma arabica (400 mg/kg, p.o.) versus ethanol-induced gastric ulcer.

Incidence

Absolute Ulcer Percentage of

value Percent index inhibition

Control 8/8 100.0 3.88 ± 0.125 0.0

Caralluma arabica 4/6 66.7 1.33 ± 0.56* 65.7
400 mg/kg, p.o.
Caralluma arabica 8/8 100.0 3.25 ± 0.31 16.2
400 mg/kg, p.o.
after indometh.
treatment

* Significantly different from control value at P < 0.05.

mucosa against gastric lesions induced by pyloric ligation extract (400 mg/kg) restored the lowered value of gastric wall
(by about 90% compared with control values). content of mucin in cold restraint stress gastric ulcer from
24.7 ± 2.8 to 53.9 ± 6.7 mg/g (wet weight).

Effect of pretreatment with indomethacin on

cytoprotective activity of C. arabica in ethanol-induced
gastric ulcer
Acute oral treatment with C. arabica extract did not show
any protective effect in ethanol–induced gastric ulcer in rats
pretreated with indomethacin (Table 4). The cytopreotective
properties of C. arabica extract against ethanol-induced
gastric mucosal damage shown in the present study was
abolished when rats were pretreated with indomethacin.
Effect on gastric wall mucin content
Cold restraint stress-induced ulcer significantly reduced
gastric wall content of mucin from 48.6 ± 5.5 to 24.7 ±
2.8 mg/g (wet weight). Acute oral treatment with C. arabica
Effect on gastric secretions and acidity
Acute oral treatment with C. arabica extract at a dose of
400 mg/kg, significantly reduced total gastric acidity
(from 22.4 ± 1.5 to 9.2 ± 1.6 mEq/L) and volume of gastric
secretions (from 9.98 ± 0.7 to 2.03 ± 0.2 ml), as shown in
Table 5.
Discussion
The results of the present investigation show antigastric ulcer
properties of a 10% ethanolic extract of C. arabica extract as
demonstrated by all experimental gastric ulcer models used
in the present study. Many factors and mechanisms are
implicated in the ulcerogenesis and gastric mucosal damage
 Anti-ulcer and cytoprotective properties of Caralluma arabica
Table 5. Effect of Caralluma arabica (400 mg/kg, p.o.) on gastric acidity in fasting Sprague-Dawley rats after pyloric ligation.
Incid. of Ulcer Initial
Treatment ulcer index pH
Controla 10/10 2.50 ± 0.22 2.53 ± 0.05
(100.0)
Controlb 9/10 2.40 ± 0.40 3.09 ± 0.22
(90.0)
Caralluma arabica 2/8 0.25 ± 0.16* 4.08 ± 0.50*
(400 mg/kg, p.o.) (25.0)
a = Water was given.
b = Water was not given.
* Significantly different from control value at P < 0.05.
induced by the different models used in the present study
involving the increase of gastric acid output, vascular injury,
depletion of gastric wall mucin, mucosal damage induced by
nonsteroidal anti-inflammatory drugs (e.g., phenylbutazone
and indomethacin) and free radical production (Galvin &
Szabo, 1992).
In the present study, C. arabica extract protected the
gastric mucosa against ulcers induced by necrotizing agents.
The cytoprotection was due to the ability of prostaglandins
to reduce the severity of the gastric injury induced by noxious
agents (Robert, 1984). Indomethacin, reported to be a potent
inhibitor of prostaglandin synthesis (Vane, 1971), was able
to abolish the cytoprotective activity of C. arabica extract in
ethanol-induced gastric ulcer, indicating the involvement of
prostagandins in mediating the antigastric ulcer properties
of C. arabica extract. Prostaglandins were reported to inhibit
the release of the pro-inflammatory mediators including
histamine, platelet activating factors and cytokins from
gastric mucosa.
The finding that C. arabica extract was able to inhibit the
gastric acid secretion in pylorus ligated animals in the present
study provides evidence for the gastroprotective properties of
the plant extract by inhibition of the ulcer produced by the
corrosive effect of the accumulated gastric secretions (Dai &
Ogle, 1974). In the present investigation, C. arabica extract
restored the marked reduction in the gastric wall content of
mucin induced by cold restraint stress injury. Inhibition of
the gastric mucus coat has been considered to be a patho-
genic mechanism of the gastric mucosal damage induced by
stress (Koo et al., 1986).
Results of the present study show that the C. arabica
extract protects gastric mucosal cells against experimental
gastric mucosal damage. This effect supports anti-
inflammatory properties of the same plant extract (Zakaria et
al., 1999) and confirms results of the studies on other species
of Caralluma (Al-Harbi et al., 1994) and seems to be medi-
ated through multiple mechanisms including increased
gastric production of prostaglandins and mucin and reduced
gastric acidity.
229
Vol. of Vol. of Gastric
gastric 0.1 N acidity
juice NaOH used mEq/L Total acidity
9.98 ± 0.71 6.15 ± 0.40 2.30 ± 0.21 22.4 ± 1.47
7.56 ± 1.26 5.14 ± 1.10 2.44 ± 0.25 18.7 ± 4.01
2.03 ± 0.22* 2.53 ± 0.43* 4.64 ± 0.77 9.23 ± 1.59*
References
Ahmad MM, Qureshi S, Shah A, Qazi NS, Rao RM, Al-Bakiri
M (1993): Anti-inflammatory activity of Caralluma tuber-
culata alcoholic extract. Fitoterapia 46: 357–360.
Al-Harbi MM (1994): Evaluation of Caralluma tuberculata pre-
treatment for the protection of rat gastric mucosa against
toxic damage. Toxicol Appl Pharmacol 128: 1–8.
Bhargava KP, Nuptial MB, Tangri KK (1973): Mechanism of
ulcerogenic activity of indomethacin and oxyphenbuta-
zone. Euro J Pharmacol 22: 191–195.
Chiu PJS, Gerhart C, Brown AD, Barenett A (1984): Effect
of gastric anti-secretory-cytoprotective 2-methyl-8-
(phenylmethoxy) imidazo (1,2-3-acetonitrile (Sch 28 080)
on cysteamine, reserpine and stress ulcers in rats.
Arzneimittel Forschung 34: 783–786.
Corne SJ, Morrisey SM, Wood RJ (1974): A method for quan-
titative estimation of gastric barrier mucus. J Physiol 242:
116–117.
Dai S, Ogle CW (1974): Gastric ulcers induced by acid accu-
mulation and by stress in pylorus-occluded rats. Eur J
Pharmacol 26: 15–21.
Galil AA, Marshal PB (1968): Phenylbutazone and histamine in
rats glandular stomach: Its relationship to gastric ulcera-
tion. Brit J Pharmacol Chemother 33: 1–14.
Galvin G, Szabo S (1992): Experimental gastric mucosal injury:
Laboratory models reveal mechanism of pathogenesis and
new therapeutic strategies. FASEB J 6: 825–831.
Koo MWL, Ogle CW, Cho CH (1986): Effect of verapamil car-
benoxolane and N-acetylcysteine on gastric wall mucus and
ulceration in stress rats. Pharmacology 32: 326–334.
Leveine RJ (1971): A rapid production of stress ulcers in rats.
In: Pfeffer CJ, Munkagaard P, eds. Peptic Ulcers Copen-
hagen. pp. 92–97.
Robert A (1984): Cytoprotection: What it is and what it is not.
In: Mechanisms of mucosal protection in the upper gas-
trointestinal tract, ed. Allen A, Flemstrom G, Garner A,
Silen W, Turnbegt L. Raven Press, New York.
Robert A, Nezamis JE, Lancaster C, Hanchar J (1979): Cyto-
protection in rats. Prevention of gastric necrosis produced
230 M.N.M. Zakaria et al.

by alcohol, HCl, NaOH, hypertonic NaCl and thermal
injury. Gastroenterology 77: 433–443.
Shay H, Komarov SA, Fels SS, Meranza D, Grunstein M, Siplet
H (1945): A simple method for uniform production of
gastric ulceration in rat. Gastroenterology 5: 43–61.
Vane JR (1971): Inhibition of prostaglandin synthesis as
mechanism of action for aspirin-like drugs. Nature 231:
232–235.
Zakaria MNM, Islam MW, Radhakrishnan R, Chen HB, Ismail
A, Chan K, Habibullah M (1999): Evaluation of anti-
nociceptive and anti-inflammatory properties of Caralluma
arabica. J Pharmacy Pharmacol 51 (Suppl.): 117.