British Journal of Pharmacology and Toxicology 3(5): 197-204, 2012

ISSN: 2044-2459; E-ISSN: 2044-2467

© Maxwell Scientific Organization, 2012
Submitted: April 12, 2012 Accepted: May 06, 2012 Published: October 25, 2012

Prophylactic Role of Echinacea, Green Tea and Boswellia Extracts in Pyloric

Ligation-Induced Gastric Ulcer in Rats
1
Souty M. Sharkawi, 1Gamal Ahmed El-Sherbiny, 2Afaf A. Ain-Shoka and 2Mostafa E. El-Sayed
1
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Beni-Suief University, Egypt
2
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Egypt

Abstract: Peptic ulcer is a common disorder of the stomach and duodenum. Herbs and medicinal plants are
considered to be a potential source to combat various diseases including gastric ulcer. The present study was
conducted to evaluate the gastro protective effects of Echinacea extract, Green tea extract and Boswellia extract on a
pyloric ligation-induced gastric ulcer. Six groups of rats were intraperitoneally pre-treated with saline as normal
group, saline as ulcer group, 20 mg/kg of ranitidine as positive group, Echinacea extract (25 mg/kg, I.P), Green tea
extract (25 mg/kg, I.P) and Boswellia extract (200 mg/kg, I.P) for 15 consecutive days before pyloric ligation.
Gastric acidity, ulcer index and histology were assessed. Gastric homogenates were determined for
Malondialdehyde (MDA) content, Glutathione (GSH) content in addition to blood Superoxide Dismutase (SOD)
activity. Pyloric ligation elevated gastric acidity, ulcer index and malondialdehyde content, while glutathione
content and superoxide dismutase activity were significantly decreased. Prior administration of extracts mitigated
the injurious effects of pyloric ligation. Echinacea, Green tea and Boswellia extracts separately ameliorated all the
altered biochemical parameters. These results were confirmed histologically. These data suggested that Green tea,
Echinacea or Boswellia extract could have a protective role in gastric ulcer probably via regulation of oxidant/anti-
oxidant balance.

Keywords: Boswellia, echinacea, gastric ulcer, green tea, pyloric ligation

INTRODUCTION properties (Agnew et al., 2005; Aherne et al., 2007;

Masteikova et al., 2007).
Peptic ulcer embraces both gastric and duodenal Tea is second only to water in popularity as a
ulcers and has been a major threat to the world’s beverage. Green tea (Camellia sinensis) is rich in
population over the past 2 centuries, with a high flavanols known as catechins such as epicatechins
morbidity and substantial mortality (Pahwa et al., (Graham, 1992). Green tea polyphenols are potent free
2010). Ulceration of the gastrointestinal mucosa is radical scavengers due to the hydroxyl groups in their
caused by disruption of normal balance of the corrosive chemical structure.
effect of gastric juice and the protective effect of mucus The plant Boswellia serrata (Family Burseraceae)
on gastric epithelial cells. Pyloric ligation induces is commonly known as Indian Olibanum in English and
gastric ulceration in rats through accumulation of acidic is reported to have antiulcer activity Zeeyauddin et al.
gastric juice in the stomach. It alters the cytoprotective (2011), Ammon (1996) and Hostanska et al. (2002)
prostaglandins, membrane lipid per oxidation and indicated that boswellic acids have a number of effects
endogenous glutathione content (Singh et al., 2008). including anti-inflammatory, immunomodulatory, anti-
Some plant extracts are recognized as sources of tumor and antioxidant.
natural antioxidants that can protect against oxidative The aim of the present study is to investigate the
stress and thus can play an important role in the possible protective effects of Echinacea extract, Green
chemoprevention of diseases resulting from lipid per tea extract and Boswellia extract in pyloric ligation-
oxidation (Nakatani, 2000). Echinacea species are rich induced gastric ulcer models. Ranitidine was chosen as
in bioactive metabolites such as alkamides, water- the reference standard in gastric ulcer protection.
soluble phenolic compounds (mainly caffeic acid
derivatives) and polysaccharides. It has been reported MATERIALS AND METHODS
that Echinacea extract possesses multifunctional effects,
such as immune stimulating, anti-inflammatory, Drugs and chemicals: All chemicals for laboratory
antiviral, anticancer and radio protective effects in experimentation were purchased from Sigma-Aldrich
addition to anti-oxidative and free radical scavenging (St. Louis, MO, USA). Green tea extract was obtained

Corresponding Author: Souty M. Sharkawi, Department of Pharmacology and Toxicology, Faculty of Pharmacy, Beni-Suief
University, Egypt
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 Br. J. Pharmacol. Toxicol., 3(5):197-204 , 2012

by Mepaco Company, Egypt and defined as having a Mihara and Uchiyama (1978). The stomach content of
polyphenolic content of 55±5%. Echinacea extract was glutathione was determined in stomach homogenate
supplied by Mepaco Company, Egypt. Boswellia according to the method of Beutler et al. (1963).
extract has been prepared according to the method Superoxide dismutase activity was determined in blood
described by Singh et al. (1996). following the pyrogallol autoxidation method of
Marklund and Marklund (1974).
Animals: Adult albino rats, weighing 140-160 g each, For histopathological examination, stomachs were
were used. Rats were obtained from the Research fixed in 10% formaldehyde solution, sectioned and
Institute of Ophthalmology (Giza, Egypt) and were kept embedded in paraffin then stained with hematoxylin
under appropriate laboratory conditions. They were and eosin and then examined under a light microscope.
kept under standard conditions of temperature (25±2°C) The specimens were assessed according to the criteria
with 12 h light/12 h dark cycle throughout the period of of Laine and Weinstein (1988).
investigation. They were fed a standard diet and
allowed free access to water. All procedures in this Statistical analysis: Data analysis was achieved using a
study were carried out according to guidelines of Ethics software program Prism (version, 5). Data were
Committee of Faculty of Pharmacy, Cairo University. presented as means±S.E. Comparisons between
different treatments were done using one way ANOVA
Experimental design: followed by Student-Newman-Keuls as a post-ANOVA
Gastric ulcer: A total of 60 rats were allocated in six test. Criterion for significance was chosen to be at
groups, 10 rats each group. First group served as p<0.05.
normal group and second group served as control group
and were given saline once daily for 15 consecutive RESULTS
days. Third group, fourth group, fifth group and sixth
group were administered ranitidine (20 mg/kg, IP), Effect of administration of ranitidine, echinacea
Echinacea extract (25 mg/kg, IP), Green tea extract (25 extract, green tea extract as well as boswellia extract
mg/kg, IP) and Boswellia extract (200 mg/kg, IP) individually for two weeks before pyloric ligation on
respectively for 15 consecutive days. All drugs and gastric acidity and ulcer index: Pyloric ligation
extracts were prepared in saline by aid of 1% Tween induced gastric ulcer with a significant increase in both
80. Animals were individually housed in a metal cage titratable acidity and ulcer index. Treatment with
with a wide-meshed bottom to prevent coprophagy. The ranitidine, Echinacea extract, Green tea extract as well
animals were fasted for 48 h but allowed free access to as Boswellia extract significantly reduced titratable
water except for the last hour before pyloric ligation. acidity to about 55.95, 66.08, 62.00 and 74.01%,
Pyloric ligation method was performed according to the respectively compared to the ulcer control value
method of Shay (1945) and Kurasawa et al. (2005). (Table 1).
Similarly, ranitidine, Echinacea extract, Green tea
Biochemical examination: Titratable acidity was
extract as well as Boswellia extract significantly
determined according to the method described by
Grossman (1963). Ulcer index was calculated according inhibited ulcer index by 48.20, 33.18, 41.67 and
to the method described by Shay et al. (1954) and the 24.12%, respectively compared to the ulcer control
protection percentage was calculated by the method value. The inhibition of ulcer index produced by Green
described by Hano et al. (1976). tea extract was similar to that produced by ranitidine,
Lipid peroxides were determined in gastric while the inhibition of ulcer index produced by
mucosal homogenate as Thiobarbituric Acid Reactive Echinacea extract or Boswellia extract was significantly
Substances (TBARS) as MDA following the method of lower than that produced by ranitidine (Table 2).

Table 1: Protective effect of two weeks daily treatment with ranitidine, echinacea extract, green tea extract or boswellia extract on ulcer index in
pyloric ligation-induced gastric ulcer in rats
Titratable acidity
------------------------------------------------------------------------------------
Drugs and doses X±SEM (mEq/L) Ulcer control (%)
Ulcer control (pyloric ligation) 94.58±7.21 100.00
Ranitidine (20 mg/kg) 52.92b±6.32 55.95b
Echinacea extract (25 mg/kg) 62.50b±5.92 66.08b
Green tea extract (25 mg/kg) 58.64b±5.22 62.00b
Boswellia extract (200 mg/kg) 70.00b±5.71 74.01b
Each value represents the mean of 10 experiments ±SEM; Statistical analysis was carried out by one way Analysis of Variance (ANOVA)
followed by Student-Newman-Keuls multiple comparisons test; b: Significantly different from ulcer control value at p<0.05

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 Br. J. Pharmacol. Toxicol., 3(5):197-204 , 2012

Table 2: Protective effect of two weeks daily treatment with ranitidine, echinacea extract, green tea extract as well as boswellia extract on ulcer
index in pyloric ligation-induced gastric ulcer in rats
Ulcer index
-------------------------------------------------------------------------------------
Drugs and doses X±SEM Protection (%)
Normal control (1% tween 80) 0.85±0.02 96.51
Ulcer control (pyloric ligation) 24.38a±0.98 00.00a
b
Ranitidine (20 mg/kg) 12.63 ±0.26 48.20b
Echinacea extract (25 mg/kg) 16.29b,c ±1.02 33.18b,c
Green tea extract (25 mg/kg) 14.22b±0.49 41.67b
Boswellia extract (200 mg/kg) 18.50b,c±1.12 24.12b,c
Each value represents the mean of 10 experiments ±SEM; Statistical analysis was carried out by one way Analysis of Variance (ANOVA)
followed by Student-Newman-Keuls multiple comparisons test; a: Significantly different from normal control value at p<0.05; b: Significantly
different from ulcer control value at p<0.05; c: Significantly different from ranitidine value at p<0.05

Fig. 2: Protective effect of two weeks daily treatment with

ranitidine, echinacea extract, green tea extract as well
as boswellia extract on gastric mucosal glutathione
content in pyloric ligation-induced gastric ulcer in rats
Fig. 1: Protective effect of two weeks daily treatment with Each bar represents the mean of 8-12 experiments;
ranitidine, echinacea extract, green tea extract as well Statistical analysis was carried out by one way
as boswellia extract on gastric mucosal Analysis of Variance (ANOVA) followed by Student-
malondialdehyde content in pyloric ligation-induced Newman-Keuls multiple comparisons test; a:
gastric ulcer in rats Significantly different from normal control value at
Each bar represents the mean of 8-12 experiments; p<0.05; b: Significantly different from ulcer control
statistical analysis was carried out by one way value at p<0.05
Analysis of Variance (ANOVA) followed by Student-
Newman-Keuls multiple comparisons test; a:
Significantly different from normal control value at
p<0.05; b: Significantly different from ulcer control
value at p<0.05

Effect of administration of ranitidine, echinacea

extract, green tea extract as well as boswellia extract
individually for two weeks before pyloric ligation on
oxidative stress biomarkers: Pyloric ligation
significantly increased gastric mucosal MDA content
compared to normal control value. Pre-treatment with
ranitidine, Echinacea extract, Green tea extract as well
as Boswellia extract significantly reduced gastric Fig. 3: Protective effect of two weeks daily treatment with
mucosal MDA content to 72.14, 69.48, 59.93 and ranitidine, Echinacea extract, Green tea extract as well
68.13%, respectively compared to the ulcer control as Boswellia extract on blood superoxide dismutase
activity in pyloric ligation-induced gastric ulcer in rats
value (Fig. 1). Each bar represents the mean of 8-12 experiments;
Pyloric ligation induced a significant decrease in Statistical analysis was carried out by one way
GSH content in rat gastric mucosa compared to normal Analysis of Variance (ANOVA) followed by Student-
control value. Administration of ranitidine, Echinacea Newman-Keuls multiple comparisons test; a:
Significantly different from normal control value at
extract, Green tea extract as well as Boswellia extract p<0.05; b: Significantly different from ulcer control
significantly increased mucosal GSH content to 300.00, value at p<0.05
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218.52, 370.37 and 296.30, respectively compared to (Fig. 4c). Echinacea extract and Green tea extract
the ulcer control value (Fig. 2). showed partial loss of mucosal surface, sub mucosal
Pyloric ligation significantly decreased blood SOD congestion, interruption of serosal layer and no necrosis
activity. Ranitidine, Echinacea extract, Green tea (Fig. 4d and e). Boswellia extract showed mild blood
extract and Boswellia extract significantly increased vessels congestion, mild tissue infiltrations, no necrosis
blood SOD activity by 142.83, 163.27, 159.76 and and no ulcers (Fig. 4f).
195.99%, respectively as compared to the ulcer group
(Fig. 3). DISCUSSION

Histopathological examination: Figure 4a shows a Pyloric ligation causes ulceration mainly via
normal histological structure of rat gastric mucosa. increased accumulation of gastric acid and pepsin
Pyloric ligation resulted in severe congestion of blood leading to auto digestion of gastric mucosa (Jainu and
vessels, hemorrhage, tissue infiltrations, tissue necrosis, Devi, 2006). In the present study, pyloric ligation
edema and several ulcers (Fig. 4b). Ranitidine showed significantly increased gastric acidity and ulcer index
better protection of gastric mucosa as seen by mild which is in consistence with the results of Sood and
blood vessels congestion and mild tissue infiltrations Muthuraman (2009).

(a) (b)

(c) (d)

(e) (f)

Fig. 4: Photomicrograph of stomach sections from normal rats, (a) pyloric ligated rats, (b) rats treated with 20 mg/kg ranitidine,
(c) 25 mg/kg echinacea extract, (d) 25 mg/kg green tea extract, (e) 200 mg/kg boswellia extract (f) (H and E stain x200)

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According to the results of the present mucosal glutathione content may be attributed to
investigation, ranitidine significantly decreased gastric increase in calcium level which stimulates free radical
acidity and ulcer index. These findings are in agreement generation (Lutnicki et al., 1992). This increase in free
with the results obtained by Kim et al. (2005). The radicals is documented to induce peptic ulcer
effect of ranitidine is mediated through histamine (Rainsford, 1999) and triggers a cascade of events
receptors. H2-receptor on the parietal cell mediates the leading finally to cell death (Orrenius et al., 1991).
stimulatory effect of histamine on acid secretion. Similarly, results of the present study revealed that
Ranitidine, a histamine H2-receptor antagonist, blocks pyloric ligation decreased blood SOD activity. This
the H2-receptors results in a decrease in the secretory result is in agreement with the work of Kath and Gupta
actions of gastrin and acetylcholine on parietal cells (2006). The reduction of SOD activity could be
(Norlen et al., 2005). attributed to the increase in free radical generation
The results of the present study showed that the (Lutnicki et al., 1992) where SOD protects organisms
tested extracts have an effective antisecretory and from ROS-mediated damage to cell components
antiulcer activity against pyloric ligation-induced (Halliwell and Gutteridge, 1990).
gastric ulcer in rats. Green tea extract significantly In the current study, ranitidine decreased gastric
decreased gastric acidity. Studies of Rao and mucosal MDA content which is in agreement with
Vijayakumar (2007) revealed that catechin, one of the Dursun et al. (2009). It has been reported that ranitidine
main active constituents of Green tea extract, caused has antioxidant and immunosuppressive actions, which
reduction in histamine concentration and attenuated the may also be responsible for its anti-ulcerative activity
elevated mucosal H+K+ATPase (the enzyme responsible (Van Zyl et al., 1993; Ardestani et al., 2004).
for H+ secretion by the gastric parietal cells) in gastric The present data revealed that ranitidine increased
mucosal injury induced by ischaemia-reperfusion. gastric GSH content and blood SOD activity which is in
Similarly, treatment with Boswellia extract harmony with that of Panneerselvam and Arumugam
significantly decreased gastric acidity which is in (2011) and Kath and Gupta (2006) respectively. GSH
accordance with results of Singh et al. (2008). detoxifies hydrogen peroxide (H2O2) and/or organic
Boswellic acids increase in synthesis of cytoprotective acids chemically; H2O2 accumulates in the absence of
prostaglandins (Singh et al., 2008). Prostaglandins GSH (Dalle-Donne et al., 2003) and in the presence of
produce a wide variety of actions in the stomach transition metals, H2O2 reacts with superoxide anion
including control of acid secretion, bicarbonate resulting in the formation of hydroxyl radical, the most
secretion, mucosal blood flow and mucus production reactive and cytotoxic form of ROS (Malo and Wilson,
(Takeeda et al., 2004). PGE2 inhibits gastric acid 2000). Ranitidine was also reported to stimulate
secretion through EP3 receptors which inhibit glutathione reductase activity (Dengiz et al., 2007).
H+K+ATPase (Hoogerwerf and Pasricha, 2006). Results of the present study showed that
Quercetin, an active constituent of Boswellia extract, Echinacea extract decreased gastric mucosal MDA
was reported to decrease the number of mast cells and content. Similar results have been reported by Kour and
to reduce the area of gastric erosions (Kahraman et al., Bani (2011) using chicoric acid which is the main
2003). These results suggest that the gastro protective active constituent of Echinacea extract. In addition, the
effect of quercetin could be due to its antioxidant and reduction in MDA content induced by Echinacea
antihistaminic effects. extract could be related to its antioxidant activity
Echinacea extract significantly decreased gastric including free radical scavenging (Agnew et al., 2005)
acidity. However, no studies were reported about the and transition metal chelating properties (Hu and Kitts,
effect of Echinacea extract on gastric acid secretions. 2000).
Study of oxidative stress parameters showed that The present data showed that Echinacea extract
pyloric ligation resulted in a significant increase in increased gastric mucosal GSH content. Several studies
gastric mucosal MDA content along with a decrease in reported that caffeic acid phenethyl ester (one of the
gastric mucosal GSH content and blood SOD activity. main active constituents of Echinacea) scavenges free
These results are in accordance with those obtained by oxygen and increases the antioxidant enzyme activity
Sood and Mutharaman (2009) and Kath and Gupta (Gurel et al., 2004).
(2006) respectively. Several studies demonstrated that In the present study, Echinacea extract increased
pyloric ligation alters the cytoprotective prostaglandins, blood SOD activity. Mishima et al. (2004) assumed that
membrane lipid per oxidation and endogenous SOD activity in peripheral blood was increased because
glutathione content (Singh et al., 2008). of antioxidants such as echinacocide and caffeine acid
Depletion of gastric mucosal glutathione content in in Echinacea extract.
counteracting free radicals and reactive oxidant In the current study treatment with Green tea
intermediates leads to gastric ulcer (Demir et al., 2003). extract significantly reduced gastric mucosal MDA
In the present study, pyloric ligation resulted in a content which is in harmony with the data obtained by
significant decrease in gastric mucosal GSH content. Adhikary et al. (2011) using epigallocatechin gallate. It
This result is in harmony with those obtained by Sood was reported that epicatechines can react with
and Mutharaman (2009). The reduction of gastric superoxide radical to form the corresponding
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 Br. J. Pharmacol. Toxicol., 3(5):197-204 , 2012

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