GASTROPROTECTIVE EFFECT OF ARTICHOKE (CYNARA SCOLYMUS L.) LEAVES AND PULP EXTRACTS ON PEPTIC ULCER IN MALE RATS

Introduction
Ulcers are deep lesions penetrating through the entire thickness of the gastrointestinal tract (GIT) mucosa and muscular mucosa (Kaur et al., 2012). Peptic ulcers are a broad term which includes ulcers of the digestive tract in the stomach or the duodenum. Recent research has shown that this ulcer developed due to aggressive factors; infection caused by bacteria Helicobacter pylori or reaction to certain medicines as nonsteroidal anti-inflammatory drugs (NSAIDs) is the causative agent of the disease (Bandyopadhyay et al., 2001). Many factors such as gastric acid and pepsin secretion, gastric microcirculation, prostaglandin E2 (PGE2) content (Laine et al., 2008).
 The increasing widespread consumption of aspirin/ NSAIDs, however, is associated with an increasing incidence of their well-known gastrointestinal complications, which include dyspepsia, gastric and/or duodenal erosions and ulcers and peptic ulcer complications (George et al., 2005). Peptic ulcer complications, usually bleeding, represent the most frequent serious adverse events of the use of aspirin/NSAIDs (Lauer, 2002). Use of NSAIDs has also been shown to increase the risk of lower gastrointestinal bleeding (Laine et al., 2003) .The gastric mucosa has evolved to tolerate the high acidity of the stomach lumen via an intricate equilibrium of protective mechanisms. The gastric protective mechanisms (preepithelial, epithelial, and subepithelial factors) act in concert (Aric et al.,2010).
 In recent years, there has also been growing interest in alternative therapies and the use of natural products, especially those derived from plants. Plant extracts are some of the most attractive sources of new drugs and have been shown to produce promising results for the treatment of gastric ulcer (Schmeda-Hirschmann and Yesilada, 2005).
 Artichoke (Cynara scolymus L.) is one of the famous traditional medicinal plants that is widely grown in Mediterranean countries and is rich in natural antioxidants (Joy and Haber, 2007 and Mehmetcik et al., 2008). Traditionally, Artichoke leaves were used for the treatment and prevention of many diseases. Artichoke has been used to treat dyspepsia mainly because of its choleretic effect that is associated with increased bile formation (Saénz et al.,2002). Artichoke extracts have been found to exhibit hepatoprotective activity (Mehmatcik et al.,2008); lipid lowering property (Qiang et al.,2012); antioxidant effect (Juzyszyn et al.,2008) and reduce postprandial blood glucose (Loi et al.,2013) in man and experimental animals. Artichoke extracts also produced protective effects against hepatocellular carcinoma both in vitro (Miccadei et al., 2008) and in vivo (Metwally et al., 2011).
 Therefore, the present study was designed to determine the gastroprotective effect of artichoke leaves and pulp extracts on aspirin induced ulcer in male rats.
MATERIALS AND METHODS
Materials
Plant:
 Fully mature Artichoke (Cynara scolymus, CV Balady, Family Asteraceae) plant was purchased from green grocery market. Both leaves and pulps (hearts) were separated, pulverized, freezing dried, and kept till preparation of aqueous extracts.
Animals:
Forty- two male albino rats, Sprague-Dawley strain weighing 160±10g, were obtained from the Laboratory Animal Colony, Helwan, Egypt.

Aspirin (Acetyl salicylic acid):
It was obtained in the form of 1 gm vial from the Ameriya Company for pharmaceutical and chemical industries, Cairo, Egypt. It was freshly prepared by dissolving one vial (1g) of aspegic in 5ml distilled water. Aspirin solution was orally given to rats on an empty stomach at a single dose of 2ml (equal to 400 mg aspirin) for induction of acute gastric ulcer.
Kits:
Kits for biochemical analysis were purchased from Gama trade for company pharmaceutical and chemicals, Dokki, Giza.
Methods:
Preparation of the basal diet
The basal diet was prepared according to the recommended dietary allowances for rats (American Institute of Nutrition, AIN) adjusted by Reeves et al. (1993). Basal diet consisted of 14 % casein , 10 % sucrose, 5 % corn oil, 0.25% choline chloride, 1% vitamin mixture (Campbell, 1963) , 3.5 % salt mixture ( Hegested et al., 1941) , 5% fibers and the remainder was corn starch up to 100 %.
Preparation of aqueous extracts:
The leaves of artichoke were removed from the pulps (hearts or heads) and both of them were dried in shade and pulverized. The powdered plant materials 200 g of leaves and 200 g of pulps were separately soaked in 1 liter of hot water at 60 °C for 3 hours, then filtered through double layers of muslin and centrifuged at 4000 rpm for 15 minutes to remove any plant debris. The aqueous extracts were freezing dried and stored at -20°C till used. This procedure was described by Shalaby and Hamowieh , (2010).
Detection of active constituents of artichoke leaves and pulp aqueous extract:
The qualitative chemical determination of active constituents of artichoke leaves and pulp aqueous extract were performed to find the presence of the major chemical constituents including; alkaloids, flavonoids, glycosides, saponins, tannins, resins and triterpenoids using standard procedures of analysis according to Harborne ,(2007).
Experimental design
All Animals were fed on the basal diet and water adlibitum and they were maintained under healthy conditions of humidity, temperature (20-25°C) and light (12-h light: 12-h dark cycle) for one week before starting the experiment for acclimatization .After an acclimatization period, rats were divided into six groups of equal weight and number (7 rats each).Group (I): was kept as a negative control group and Group (2): was kept as a positive control group. These two groups were fed on the basal diet and given orally saline at volume of 1.0 ml/ 100 g b.wt) for four weeks. Group(3) was fed on basal diet and orally given the aqueous extract of artichoke leaves(ALE) in a dose of 200 mg/kg b.wt, Group(4) : was fed on basal diet and orally given the aqueous extract of artichoke leaves(ALE) in a dose of 400 mg/kg b.wt, , Group(5) : was fed on basal diet and orally given the aqueous extract of Artichoke pulp (APE) in a dose of 200 mg/kg b.wt, Group(6): was fed on basal diet and orally given the aqueous extract of artichoke pulp (APE) in a dose of 400 mg/kg b.wt, for four weeks .On the last day of the experimental period (28 days), all rats were starved of food, but not of water for 24 hours and groups 2,3,4,5 and 6 orally given aspirin at a single dose of 2ml according to Agrawal et al., (2000) . The rats were sacrificed after 4 h of administration of aspirin. Then the blood was collected under diethyl ether anesthesia and centrifuged to obtain the serum which used for biochemical analysis. Stomach was taken for determination of biomarkers of gastric ulcer and histopathological examination.
Gastric ulcer index
The method described by Agrawal et al., (2000) was employed in the present study. In brief, after 4 hours of aspirin administration, all rats were sacrificed after using an overdose of diethyl ether and their stomachs removed and washed with saline. The gastric juice was collected in a test tube. Then stomachs were opened along the greater curvature, washed with saline and examined under a dissecting microscope for gastric ulcers. The sum of the length of all lesion areas for each animal was measured and
served as the ulcer index. The curative ratio was calculated for each group using the following equation:
Curative ratio (CR) = (LC-LT/LC) x100
LC: The length of gastric ulcer in positive group.
LT: The length of gastric ulcer in treated group
Determination of gastric juice acidity
The total acidity was determined according to the method described in A.O.A.C. (1995). Percentages of the decrease in total acidity of gastric juice of the treated group compared to the positive (C+Ve) control group were calculated using the following equation:
Percentage of the decrease =    × 100
Where:
TAC =Total acidity of gastric juice of the positive control group.
TAT =Total acidity of the gastric juice of the treated group.
Determination of gastric juice volume
Gastric juices from all groups were collected in test tubes, centrifuged at 5000 r.p.m. for 10 minutes and their volume of were measured by a graduated cylinder . percentages of the decrease in volume of the gastric juice of the treated groups compared to the positive (C+ve) control group were calculated according to the method described by Agrawal et al., (2000) using the following equation:
Percentage of the decrease =   ×100
Where:
VJC = volume of gastric juice of the positive control group.
VJT = volume of gastric juice of the treated group.

Determination of pepsin concentration in gastric juice:
 Concentrations of pepsin (a proteolytic enzyme that degrades dietary protein) in the collected gastric juices were measured chemically using spectrophotometer at 313 nm according to the method described by Schniath (1989).
Biochemical analysis :
Activities of antioxidant enzymes such as glutathione peroxidase, superoxidase dismutase, and catalase will be determined according to (Paglia& Valentine, 1979, KaKKar et al., 1984 and Sinha, 1972, respectively) and Determination of Malondialdehyde level (MDA) was measured by the method of Mihara and Uchiyama, (1978) . Prostaglandin E2 (PGE2) assay was performed with the PGE2 enzyme immunoassay kit (R&D Systems, Inc., MN, USA) according to the supplier's instructions. Serum tumor necrosis factor (TNF-α) was determined by enzyme-linked immunosorbent assay (ELISA) using rat TNF-α assay kit (Biosource, USA) as previously described by Su et al., (2002). Interleukin-1 (IL-1) was measured by the method of Grassi et al., (1991).
Histopathological studies:
The stomach of the rats was fixed in 10% neutral formalin solution. the fixed specimens were then trimmed , washed and dehydrated in ascending grades of alcohol .these specimens were then colored in xylene ,embedded in paraffin ,sectioned at 4-6 microns thickness and stained with hematoxylin and eosin (H&E) Then examined microscopically according to Carleton, (1979).
Statistical Analysis:
 All data obtained results were analyzed using Statistical Package for the Social Sciences (SPSS) for Windows, version 20 (SPSS Inc., Chicago, IL, USA) . The collected data were presented as a mean ± standard deviation (SD). Analysis of Variance (ANOVA) test was used for determining the significances among different groups according to (Armitage and Berry, 1987). All differences considered significant if the level of P-values ˂ 0.05.
Results
The phytochemical screening of artichoke leaves aqueous extract (ALE) revealed that it contains large amounts of flavonoids and saponins; moderate amounts of alkaloids and tannins and a small amount of glycosides. Otherwise artichoke pulp aqueous extract (APE) was found to contain large amounts of flavonoids, glycosides and saponins; moderate amounts of alkaloids, and a small amount of tannins, but the extracts of leaves and pulp were devoid of resins and triterpenes as depicted in
Table (1).
Table (1). Phytochemical screening of active constituents of Artichoke  (Cynara scolymus) leaves and pulp aqueous extract .
Active constituents Alkaloids Flavonoids Glycosides Saponins Tannins Resins Triterpenes
Artichoke leaves (ALE) ++ +++ + +++ ++ -- --
Artichoke pulp(APE) ++ +++ +++ +++ + -- --
   + = Small amount       ++ = Moderate amount       +++ = Large amount         -- = Absent.
The statistical data in Table 2 showed that there was a significant increase in the volume of gastric juice of the positive control group compared to the negative control group. While, pre-treatment with aqueous extracts of both leave and pulp of artichoke in doses of 200 and 400ml/kg.B.wt., respectively, to male rats with gastric ulcer significantly decreased (P < 0.05) the volume of gastric juice by 41.42, 70.35, 43.97 and 69.08%, respectively as compared to the control positive group.
 
Table (2): The effect of aqueous extracts of Artichoke leaves (ALE) and pulp (APE) on the volume of the gastric juice against aspirin-induced gastric ulcers in rats.
Parameters
Groups Volume of gastric juice (ml)
 Mean ± SE Decrease (%) Compared with C+ve
G1: Control (C-ve) 2.02± 0.26d  ---
G2:Aspirin (C+ve) 7.05± 0.12 a ---
G3: ALE (200ml/kg.B.wt) 4.13 ± 0.11c 41.42
G4: ALE (400ml/kg.B.wt) 2.09± 0.21d  70.35
G5: APE (200ml/kg.B.wt) 3.95 ± 0.19c 43.97
 G6: APE(400ml/kg.B.wt) 2.18± 0.13d  69.08
Data are presented as means ± standard deviation, (n = 7 for each group) Values with different superscripts within the column are significantly different at P< 0.05. Values with similar or partially similar superscripts are non-significant.
As shown in Table 3 aspirin administration caused a significant increase in total acidity of gastric juice of the positive control group compared to the negative control group. Pre-treatment with aqueous extracts of both leaves and pulp of artichoke at the different doses (200 and 400ml/kg.B.wt.) to rats with aspirin-induced gastric ulcer decreased the total acidity of gastric juice by 47.94, 70.73, 40.88, and 70.46%, respectively as compared the the positive control group.
Table (3): The effect of aqueous extracts of Artichoke leaves (ALE) and pulp (APE) on the total acidity of the gastric juice against aspirin-induced gastric ulcers in rats.
Parameters
Groups Total acidity of gastric juice ( mg equiv./L)
 Mean ± SE Decrease (%)
G1: Control (C-ve) 7.12± 0.13 c ---
G2:Aspirin (C+ve) 25.76 ± 0.51a ---
G3: ALE (200ml/kg.B.wt) 13.41± 0.23b 47.94
G4: ALE (400ml/kg.B.wt) 7.54± 0.14 c 70.73
G5: APE (200ml/kg.B.wt) 15.23± 0.13b 40.88
 G6: APE(400ml/kg.B.wt) 7.61± 0.12 c 70.46
 Data are presented as means ± standard deviation, (n = 7 for each group) Values with different superscripts within the column are significantly different at P< 0.05. Values with similar or partially similar superscripts are non-significant.
Data recorded in Table ( 4 ) showed that the gastric ulcer index in male rats with experimental gastric ulcer (positive control) was 11.42 ± 0.06 mm compared to zero (no ulcer) in the negative control group (normal rats). The values of gastric ulcer index were significantly decreased in all pre-treated rat groups compared with the control positive group. The ulcer healing effect was greater by use of ALE (400ml/kg.B.wt).
Table (4): The effect of aqueous extracts of Artichoke leaves (ALE) and pulp (APE) on gastric ulcer index against aspirin-induced gastric ulcers in rats.
Parameters
Groups  Gastric ulcer index
Mean ± SE (mm) Curative ratio (%)
Compared with C+ve
G1: Control (C-ve) --- ---
G2:Aspirin (C+ve) 11.42 ± 0.06 a ---
G3: ALE (200ml/kg.B.wt) 8.31 ± 0.12 b 27.23
G4: ALE (400ml/kg.B.wt) 5.23± 0.13 c 54.20
G5: APE (200ml/kg.B.wt) 7.49± 0.04 b 34.41
 G6: APE(400ml/kg.B.wt) 5.54± 0.24 c 51.49
Data are presented as means ± standard deviation, (n = 7 for each group) Values with different superscripts within the column are significantly different at P< 0.05. Values with similar or partially similar superscripts are non-significant.
Table 5 showed that aspirin administration caused a significant increase in gastric juice pepsin activity compared to the negative control group. Meanwhile, Oral administration of ALE and APE to male rats for 4 weeks revealed significant decreases in pepsin concentration by 21.55, 42.63, 18.89 and 41.70 % , respectively as compared to the positive control group.
Table (5): The effect of aqueous extracts of Artichoke leaves (ALE) and pulp (APE) on pepsin concentrations in gastric juice against aspirin-induced gastric ulcers in rats.
Parameters
Groups  pepsin concentration (mg/ml) Compared with C+ve
 Mean ± SE Decrease (%)
G1: Control (C-ve) 27.08 ± 1.07 c ---
G2:Aspirin (C+ve) 46.12 ± 2.2 a ---
G3: ALE (200ml/kg.B.wt) 36.18 ± 1.4 b 21.55
G4: ALE (400ml/kg.B.wt) 26.46 ± 1.6 c 42.63
G5: APE (200ml/kg.B.wt) 37.41 ± 1.6b 18.89
 G6: APE(400ml/kg.B.wt) 26.89 ± 1.6 c 41.70
Data are presented as means ± standard deviation, (n = 7 for each group) Values with different superscripts within the column are significantly different at P< 0.05. Values with similar or partially similar superscripts are non-significant.
The statistical data in Table 6 presented that, control (+ve) rat group showed significant increase in lipid peroxide malondialdehyde (MDA) content and decrease in levels of reduced glutathione (GSH) when compared with the negative control group. Pre- treated rats with different doses of aqueous extracts of leaves (ALE) and pulp (APE) of artichoke significantly decreased MDA content and increased GSH content in liver tissue when compared with the positive control group.
Table (6): The effect of aqueous extract of aqueous extracts of Artichoke leaves (ALE) and pulp (APE) on serum malondialdehyde (MDA) and reduced glutathione (GSH) contents against aspirin-induced gastric ulcers in rats.
GSH (μmol/dl MDA (μmol/dl  Parameters
Groups
31.17 ± 1.34a 18.09± 1.42c G1: Control (C-ve)
18.02 ± 1.05d 29.24± 2. 11a G2:Aspirin (C+ve)
24.14 ± 2.23c 23.02± 2. 08 b G3: ALE (200ml/kg.B.wt)
30.19 ± 1.21a 18.89± 1. 23c G4: ALE (400ml/kg.B.wt)
23.29 ± 1.21c 23.92± 1. 03b G5: APE (200ml/kg.B.wt)
27.71 ± 2.65b 19.07± 1. 04c  G6: APE(400ml/kg.B.wt)
Data are presented as means ± standard deviation, (n = 7 for each group) Values with different superscripts within the column are significantly different at P< 0.05. Values with similar or partially similar superscripts are non-significant.
The results illustrated in table 7 showed that aspirin administration (control+ve group) caused a significant (p<0.05) decreases in the activity of serum superoxide dismutase (SOD), glutathione peroxidase(Gpx) and catalase (CAT) enzymes when compared with the normal control group. Oral administration of AELA and AEPA at both dosages caused a significant (p<0.05) increases in the activity of SOD, GPx, and CAT enzymes when compared with the control+ve group.
Table (7) The effect of aqueous extracts of Artichoke leaves (ALE) and pulp (APE) on activities of serum superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase (CAT) antioxidant enzymes against aspirin-induced gastric ulcers in rats.
CAT
(U/mg) GPx
(U/mg) SOD
(U/mg) Parameters
Groups
7.12 ± 1.42a 76.11 ± 1.09a 68.32 ± 1.12. a G1: Control (C-ve)
2.07± 0.13c 37. 82 ± 1.35d 31.09 ± 1.28d G2:Aspirin (C+ve)
4.56± 0.46b 65.20 ± 1.14b 51.53 ± 2.23b G3: ALE (200ml/kg.B.wt)
6.75± 1.25a 75.98±0.19a 67.97 ± 2.53a G4: ALE (400ml/kg.B.wt)
4.75± 0.75b 57.28±2.16c 57.81 ± 1.63c G5: APE (200ml/kg.B.wt)
6.99± 0.12a 75.27 ± 1.12ba 66.79 ±2.13a  G6: APE(400ml/kg.B.wt)
Data are presented as means ± standard deviation, (n = 7 for each group) Values with different superscripts within the column are significantly different at P< 0.05. Values with similar or partially similar superscripts are non-significant.
 Data reported in Table 8 showed that aspirin administration led to significant decreases in prostaglandin E2 while , there were significant increases in serum interleukin-1 and tumor necrosis factor-alpha levels compared to (-ve) control group. The pretreatment groups with aqueous extracts of leaves (ALE) and pulp (APE) of artichoke showed significant decreases in interleukin-1 and tumor necrosis factor-alpha while there was a significant increase in prostaglandin E2 compared to the ulcerated positive control group.
Table (8): The effect of aqueous extracts of Artichoke leaves (ALE) and pulp (APE) on Prostaglandin E2 (PGE2), tumor necrosis factor (TNF-α) and Interleukin-1(IL-1) against aspirin-induced gastric ulcers in rats.
IL-1
pg/ml TNF-α
pg/ml PGE2
pg/mg Parameters
Groups
13.45 ± 0.71c 4.52 ± 1.17c 470.62± 1.08 a G1: Control (C-ve)
40.32± 0.59a 13. 43 ± 1.21a 284.34 ± 0.42d G2:Aspirin (C+ve)
22.09± 0.36b 7.01 ± 0.14b 422.08 ± 1.56c G3: ALE (200ml/kg.B.wt)
12.95± 0.05c 3.99±0.26c 469.62 ± 1.52a G4: ALE (400ml/kg.B.wt)
24.23± 1.43b 6.86 ± 1.36b 393.73 ±0.78b G5: APE (200ml/kg.B.wt)
12.89± 1.43c 5.18 ± 0.39b 466.19 ± 0.91a G6: APE(400ml/kg.B.wt)
Data are presented as means ± standard deviation, (n = 7 for each group) Values with different superscripts within the column are significantly different at P< 0.05. Values with similar or partially similar superscripts are non-significant.
Histopathological studies:
Histopathological examination of the stomachs of the negative control (normal) rats revealed normal gastric layers (mucosa, submucosa, musculosa and serosaas shown in Photo. (1). The stomachs of the positive control rats (given aspirin) showed focal necrosis of gastric mucosa associated with inflammatory cells infiltration as well as submucosal oedema and inflammatory cells infiltration (Photo.2) . Examined sections of the stomachs of the rats orally given 200ml/kg.B.wt aqueous extracts of artichoke leaves showed congestion of mucosal blood vessels(Photo.3). Examined sections of rat orally given 400ml/kg.B.wt aqueous extracts of artichoke leaves showed no histopathological changes as shown in Photo. (4). The stomachs of rats orally given 200ml/kg.B.wt aqueous extracts of artichoke pulp showed slight submucosal oedema (Photo.5) Examined sections of rat orally given 400ml/kg.B.wt aqueous extracts of artichoke pulp showed apparent normal mucosa as shown in Photo. (6).
 
photo(1): stomach of normal rat group showing normal gastric layers (mucosa, submucosa, musculosa and serosa) (H&Ex100)
 
Photo(2): Stomach of positive control rats (given aspirin) showing focal necrosis of gastric mucosa associated with inflammatory cells infiltration as well as submucosal oedema and inflammatory cells infiltration (H & E X 100).
 

 
Photo (3): Stomach of rats orally given 200ml/kg.B.wt aqueous extracts of artichoke leaves showing congestion of mucosal blood vessels (H & E X 100).
 
Photo (4): Stomach of rats orally given 400ml/kg.B.wt aqueous extracts of artichoke leaves showing no histopathological changes (H & E X 100).

 
Photo (5): Stomach of rats orally given 200ml/kg.B.wt aqueous extracts of artichoke pulp showing slight submucosal oedema (H & E X 100).
 
Photo (6): Stomach of rats orally given 400ml/kg.B.wt aqueous extracts of artichoke pulp showing apparent normal mucosa (H & E X 100).

Discussion
The current study was designed to determine qualitatively the chemical constituents of aqueous extracts of Artichoke (Cynara scolymus) leaves and pulp and to assess their gastroprotective effect of artichoke (Cynara scolymus L.) on Aspirin-Induced Ulcer in male Rats.
 Nowadays, medicinal plants, vegetables, and fruits with gastric ulcer activity have gained much attention, especially those with low toxicity properties. The biological value of the plant materials depends on their bioactive chemical constituents such as saponins, anthocyanins, flavonoids, polyphenols, triterpenes and other phytochemicals (Veermuthu et al., 2006 and Patel et al., 2012.(
In this study, the phytochemical screening of both Artichoke leaves and pulp aqueous extracts showed that they contain flavonoids, alkaloids, glycosides, saponins, and tannins, but they were devoid of resins and triterpenes. These results were in harmony with the previous data obtained by (Nassar et al.,2013 , Abu-Reidah et al ., 2013 and Wu et al .,2008 ). Moreover, the two later authors (Abu-Reidah et al., 2013 and Wu et al., 2008) isolated and characterized the bioactive phenolic constituents from fresh and canned Artichoke by HPLC. The authors concluded that Artichoke plant could be regarded as a functional food and also as a promising source of potent antioxidant polyphenolic compounds (Wu et al., 2008).
The present study showed that aspirin at a dose of 400mg/kg b.wt., single dose in 24hrs fasted rats caused a significant damage to the gastric mucosa. This was evidenced by a significant decrease in gastric pH, increase in acid output, ulcer index and pepsin activity as compared to normal control (p<0.05). The ulceration induced by Aspirin is attributed mainly to various processes, including the generation of reactive oxygen species, the initiation of lipid peroxidation, infiltration of leukocytes, induction of apoptosis, and inhibition of prostaglandin synthesis (Bech et al., 2000). Decreased prostaglandin level impairs almost all aspects of gastroprotection and increases acid secretions which, in turn, aggravate the ulcer (Miller, 1983).Histological findings also supported the gastric mucosal damage. This finding was in accordance with Wallace, (2008).
The data of present study shows variable inhibitory effects of aqueous extracts of Artichoke (Cynara scolymus) leaves and pulp on total acidity, gastric volume, peptic activity, ulcer score, ulcer index and pepsin activity. These observations suggest the aqueous extracts of Artichoke (Cynara scolymus) leaves and pulp possibly have an antacid-like action. Artichoke extracts may contain biologically active substances with potential anti-ulcer properties. This gastro protective effect may be due to the high flavonoids content of Artichoke extracts (Katrin et al.,2004). The obtained results are consistent with those of Kazuo et al., (2010) who demonstrated that Artichoke possesses anti-ulcer activity against the ulceration caused by aspirin. Furthermore, Nawal and Naglaa (2016) reported that aqueous extracts of Artichoke (Cynara scolymus) leaves showed good gastro protective anti-ulcerogenic activity and they attributed this effect to the anti-oxidative activity of flavonoids found in the extract as reported by Mahmoud et al.,( 2013) and these compounds may work by relaxing the smooth muscle of the gastrointestinal tract.The results suggest that some of the constituents present in the aqueous extracts of Artichoke (Cynara scolymus) leaves and pulp may have central actions, which are helpful in reducing the gastric ulcers. The reduction may be also due to local effect on gastric motility or gastric secretion.
Oxidative stress plays an important role in the pathogenesis of various diseases including gastric ulcer. Aspirin administration was found to increase MDA level and a decrease in GSH level, as well as SOD, CAT and GPx activities in the positive control groups compared to the negative control group, thus leading to oxidative stress. Preventive antioxidants, such as superoxide dismutase (SOD) and catalase (CAT) enzymes are the first line of defence against reactive oxygen species. Reduced glutathione (GSH) is a major low molecular weight scavenger of free radicals in the cytoplasm and an important inhibitor of free radical mediated lipid peroxidation (Alfadda and Sallam, 2012). Administration of aqueous extracts of Artichoke (Cynara scolymus) leaves and pulp resulted in a significant decrease in MDA while there were significant increases in the GSH level, as well as SOD, CAT and GPx activities as compared to the positive control animals, These findings were similar to the results of the previous studies (Juzyszyn et al., 2008). Furthermore, (Magielse et al., 2014( concluded that the protective activity of Artichoke could be attributed to its constituents of many bioactive polyphenolic antioxidant compounds, mainly cynarine, luteolin, and chlorogenic acids which are abundant in both heads and leaves .
Nonsteroidal anti-inflammatory drugs (NSAIDs) such as aspirin have the ability to cause gastroduodenal ulceration and this effect is related to the ability of these agents to suppress prostaglandin synthesis (Lichtenberger et al., 2007 and Wang et al., 2007) In the stomach, prostaglandins play a vital protective role, stimulating the secretion of bicarbonate and mucus, maintaining mucosal blood flow and regulating mucosal cell turnover and repair. Thus, the suppression of prostaglandin synthesis by NSAIDs results in increased susceptibility to mucosal injury and gastroduodenal ulceration ( Deore et al., 2011). Our experimental results were in the same line with these previous data. Aspirin significantly reduced gastric mucosal prostaglandin E2 (PGE2) level compared to the negative control group. Pretreatment with aqueous extracts of Artichoke (Cynara scolymus) leaves and pulp significantly increased PGE2 levels when compared to aspirin-treated rats. This finding was explained by Sannia, (2010) who reported that flavonoids may protect the gastric mucosa from damage by increasing the mucosal prostaglandin content and by inhibiting histamine secretion from mast cells by inhibition of histidine decarboxylase.
The inflammation induced in the gastric mucosa by aspirin is accompanied by increased TNF-α production (Jainu et al., 2006), which augments neutrophil-derived superoxide generation (Kwiecien et al., 2002) and stimulates IL-1 production leading to neutrophil accumulation (Odashima et al.,2006) Over production of TNF--α increased the risk of gastric ulcer and cancer (Mitsushige et al.,2006). In the present study, the levels of TNF-α and IL-1 were increased by aspirin administration and the pretreatment with all using aqueous extracts of artichoke (Cynara scolymus) leaves to the artichoke antioxidant activity.
The alterations of serum biochemical parameters induced by Artichoke extracts were confirmed by partial regression of histopathological degenerative changes seen in the gastric of ulcerative rats. The amelioration of histopathological lesions by oral administration of both Artichoke extracts was in accordance with that previously reported by (Nawal and Naglaa, 2016) The serum and tissue biochemical changes induced by pretreatment of Aspirin- ulcerative rats with Artichoke aqueous extracts, in the present study, were to some extent parallel to the histopathological findings, denoting gastroprotective activity of Artichoke extracts.
 In conclusion, the present results denote that aqueous extracts of Artichoke leaves and pulp produce gastroprotective activity and antioxidant effects and partially alleviate the degenerative changes induced by Aspirin in gastric of rats. These findings affirm the traditional use of Artichoke plant for treating peptic ulcer diseases.