Laine et al.  stated that reactive oxygen species (ROS) generated by neutrophils in gastric mucosa has a critical role in the gastric mucosal injury. Later, Al Rashdi et al.  and Kan et al.  reported that ele- vated production of ROS and depletion of antioxidants are involved in the pathophysiology and development of ethanol-inducedgastriculcer. According to Yu et al. , accumulation of ROS leads to lipid peroxidation as a result of their reaction against cell membrane. Our data revealed that, ethanol administration significantly reduced the activity levels of antioxidant enzymes (CAT, SOD and GSH-Px) and increased the concentration of MDA with concomitant depletion in GSH concentration in the gastric tissue of ethanol group, this is in the same line with the previous studies of Sidahmed et al. . On the other hand, pre-treatment of C. ignea extract in ulcerated groups has a great efficacy in preventing free radical mediated oxidative damage by enhancing the ac- tivity of antioxidant enzymes (CAT, SOD and GSH-Px) and restoring the depleted GSH levels together with re- ducing MDA levels. This antioxidant effect of the C. ignea extract could be attributed to its strong free radical scavenging activity due to the presence of a significant amount of, the powerful antioxidants, flavonoids and phenolic compounds. This is consistent with Mei et al.  who established that one of the mechanisms re- sponsible for the healing of ulcer is scavenging of ROS. Our study showed that C. ignea extract had strong anti- oxidant effect, which is comparable to that of ranitidine. Ahmadi et al.  previously reported that therapeutic effect of ranitidine on ulcer could be related to its anti- oxidant capacity through oxidative stress reduction me- diated by scavenging of hydroxyl radical.
The acute toxicity test did not suggest any toxicity or mortality in the P. speciosa-treated rats. This test revealed that the plant is safe and has no toxicity when administered orally up to 5 g/kg. Certain antiulcer drugs have been reported to increase the amount of gastric mucus secretion in the gastric mucosa . Pretreatment with Parkia speciosa extract significantly increased the gastric mucus content in rats with ethanol-induced ulcers, indicating that the gastroprotective effect of Parkia speciosa is mediated partly by preservation of the gastric wall mucus. This mucus consists of mucin-type glycoproteins, which can be detected by Alcian blue ; the increase in Alcian blue staining demonstrates the protective effect of orally administered Parkia speciosa, which may be mediated by the formation of protective complexes between Parkia speciosa and the mucus that acts as a barrier against necrotizing agents introduced to the stomach . Here, the Parkia speciosa extract prevented the decrease in the concentration of gastric wall mucus upon treatment with ethanol. Thus, one possible mechanism by which the gastric mucosa is protected by Parkia speciosa involves the reinforcement of the mucosal barrier resistance, generated by a protective coating. It is likely that the protective effect of Parkia speciosa is due at least in part to the preservation of the mucus layer in the gastric mucosa; Parkia speciosa was observed to prevent ethanol-inducedgastric wall mucus depletion. The results of the present study demonstrated that Parkia speciosa extract has an effective antiulcer activity against Table 1. The effect of Parkia speciosa ethanolic extract on
Antiulcer activity of Cassia tora was evaluated by using ethanolinducedgastriculcer model. Ethanolinducedgastriculcer model was employed to study the cytoprotective effect of the extract. Ethanolinducedgastric lesion formation may be due to stasis in gastric blood flow which contributes to the development of the haemorrhage and necrotic aspects of tissue injury. Alcohol rapidly penetrates the gastric mucosa apparently causing cell and plasma membrane damage leading to increased intra cellular membrane permeability to sodium and water. The massive intracellular accumulation of calcium represents a major step in the pathogenesis of gastric mucosal injury. This leads to cell death and exfoliation. Studies suggest that the ethanol damage to the gastrointestinal mucosa starts with micro-vascular injury, namely disruption of the vascular endothelium resulting in increased vascular permeability, oedema formation and epithelial lifting [11-13] . These effects are secondary to ethanolinduced slowing or cessation of gastric mucosal flow  . Ethanol also produces a marked contraction of the circular muscles of rat fundic strip. Such a contraction can lead to mucosal compression at the site of the greatest mechanical stress, at the crests of mucosal folds leading to necrosis and ulceration  .
Ethanol – inducedGastricUlcer: The gastric ulcers were induced in rats of either sex weighing between 130-150 by administrating absolute ethanol (8ml/kg). They were kept in specially constructed cages to prevent coprophagia during and after the experiment. The rats were divided into nine groups each containing six animals and fasted for 24h and allowed free access to water. The first group received distilled water and second group received ethanol only. The third group received ethanol and standard anti-ulcer drugs Ranitidine (150mg/kg). The 4-6 th groups were given absolute ethanol and oil of C. halicacabum var. microcarpum at a dose of 3.3, 6.6, and 9.9ml/kg respectively. The 7-9 th group received absolute ethanol and oil of C. halicacabum var. luridum at a doses of 3.3, 6.6 and 9.9 ml/kg.
The anti ulcer activity of beta vulgaris was evaluated by employing aspirin, alcohol, and pylorus ligation inducedulcer models. These models cause the gastriculcer in humans. Many factors and mechanisms are involved in the ulcerogensis and gastric mucosal damage. Ethanolinducedgastriculcer was employed to study the cytoprotective effect of the extracts. The ethanol-induced ulcers is predominant in the glandular part of stomach and was reported to stimulate the formation of leukotriene C4 (LTC4), mast cell secretory products and reactive oxygen species resulting in the damage of rat gastric mucosa. Alcohol rapidly penetrates the gastric mucosa causing cell and plasma membrane damage leading to
scientific reports on the investigation of methanol extract of stem bark of B.purpurea for its effects on protection against ethanolinducedgastric ulceration model is scarce. In the present study, an effort has been made to evaluate the effect of the methanol extract of stem bark of this plant on ethanolinducedgastriculcer in rats and determined the activity of antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT) , reduced glutathione (GSH) and the levels of lipid peroxidation (LPO) in the stomach tissues of all treated groups to check whether B. purpurea exerts anti ulcer action by means of its antioxidant activity.
In pylorus ligation inducedgastriculcer Juglans regia.L has shown significant reduction in ulcer index when compared to that of the control. Whereas the decrease in gastric secretion volume & total acidity are not significant. It is also observed that ulcer index is significantly high in aspirin induced & ethanolinduced peptic ulcer group as compared to the Juglans regia.L extract treated group which shows marked reduction(p<0.01) in gastric lesions. In histopathological examination of stomach specimens of control group from all the models it was seen that there was extensive gastric damage, even involving all the layers of the stomach wall in some regions. The mucosal epithelial cells were completely eroded and there was severe infiltration by inflammatory cells. The submucosal layer was edematous and engorged blood vessels could be seen. The muscular layer was also edematous. However the groups treated with Juglans regia.L extract and ranitidine did not show any such findings of that extensive gastric damage.
Background: Trichopus zeylanicus Gaertn is a perennial herb, belongs to the family Trichopodaceae, is wild plant, a rare genus, small glabrous herb growing in the Agasthyar hilly forest of Kerala. The Kani tribes of this area call this plant as “Arogyapacha” or “Arokyapachilai” in Malayalam. Objective: The present study was investigated for anti-ulcer potential of Saponin fraction of the whole plant of T. zeylanicus on various experimental animal models. Materials and Methods: Acute toxicity study of saponin fraction of T. zeylanicus (SFTZ) was carried out on female albino rat up to 2000 mg/kg as per OECD guideline No.423. The experimental animal models, i.e., ethanolinducedulcer, restrained stress induced and pyloric ligation (PL) induced ulcers model were tested for anti-ulcer activity SFTZ at three various doses of (75,150 and 300 mg/kg, p.o.,) for 5 days to Wistar Albino rat. Esomeprazole (10 mg/kg, p.o.,) was used as a reference standard for the present study. Results: Treatment of SFTZ (75,150 and 300 mg/kg, p.o.,) showed a significant dose-dependent effect in lowering ulcer index with significantly increased in percentage protection against ethanol, restrained stress and PL inducedulcer model in rats. Biochemical parameter like gastric volume, pH, free acidity, total acidity total proteins, total hexoses, hexosamine, fucose, sialic acid, and pepsin were determined in PL induce ulcer models. The result showed significantly increased in level of defensive mucin secretion in terms of total carbohydrates: Protein ratio after SFTZ treated rats in PL induce ulcer models. Conclusion: The action potential of SFTZ is positively found to be more active in alleviating the ulcer by chemical and physical induced models.
It is evident from the result of the present investigation that the formulation of Ficusdalhousie possesses antiulcer activity in aspirin induced and ethanolinduced acute ulcer model. It has shown a significant reduction in the gastric lesions in both the models. Although the etiology of gastriculcer is not known in most cases, it is generally accepted that it results from an imbalance between aggressive factors and the maintenance of mucosal integrity through the endogenous defence mechanisms 8 . To regain the balance, different therapeutic agents including plant extracts are used (in experimental animals) to inhibit the gastric acid secretion or to boost the mucosal defence mechanisms by increasing mucus production, stabilizing the surface epithelial cells/or enhancing prostaglandin synthesis. Ranitidine the proton pump inhibitor play an important role in the reduction of gastric volume and total acidity and thus perform a cytoproective effect.
To further confirm its anti-ulcerogenic effect ethanol extract was evaluated for Cold-restraint stress - inducedulcer model. Gastric ulceration induced by stress is probably mediated by the presence of acid, increase in gastric motility,  mast cell degranulation, decreased gastric mucosal blood flow , decreased prostaglandin synthesis  and augmented excretion of glycoproteins in the mucus . Moreover, stress-inducedulcer can be prevented partially or entirely by vagotomy; vagal over activity has been suggested to be the principal factor in stress-induced ulceration . Any of these factors could play a role in genesis of stress-induced ulcers. Oral administration of the ethanolic extracts of Morinda citrifolia showed dose dependent inhibition of gastric ulceration induced by Cold-restraint stress.
The antiulcer effect of Semicarpus anacardium Linn. seed extracts was investigated against aspirin plus pylorus ligation induced and ethanolinducedgastric ulcers in rats. Both the models revealed ulcer healing property of the seed extracts. The present investigation also revealed the hepatoprotective activity of the seed extracts, against ethanolinduced hepatotoxicity. Histopathological studies of the liver showed significant restoration of the normal histomorphological pattern of hepatocytes. The biochemical estimation of serum bilirubin, serum glutamate pyruvate transaminase ( SGPT ), serum glutamate oxaloacetate transaminase ( SGOT ) and alkaline phosphatase ( ALP ) showed significant reduction in the rats fed with the seed extracts. The study, thus, substantiates the potential anticulcer and hepatoprotective effects of Semicarpus anacardium seeds.
On the contrary in India, herbal drugs are an integral part of the Indian system of medicine (Ayurveda) which is an ancient and main stream system. The antiulcer activity of aerial part of Argemone mexicana was investigated on ethanolinduced model and indomethacin induced model albino wistar rats. In both models the ulcer index was common and it is determined. Ethanolic extract of dose 300 mg/kg and 600mg/kg p.o. produced significant inhibition of gastric lesions induced by ethanolinduced and indomethacin induced ulcers. The extract 300mg/kg and 600mg/kg showed significant reduction in gastric acidity and ulcer index as compared to control. Phytochemical analysis showed the presence of glycosides, tannins, alkaloids,
The anti-ulcerogenic potential and antioxidant activity of ethanolic leaf extract of Mussaenda glabrata was investigated. The potential of the ethanolic extract to serve as antioxidants were assayed by DPPH and ABTS radical scavenging activity. Antiulcer activity was determined by three different models in experimental Wistar rats: Ethanolinducedulcer, Indomethacin inducedulcer and Pylorus ligation model. Oral administration of ethanolic extract of Mussaenda glabrata at 200 and 400mg/kg significantly reduced the gastric lesions with dose dependent ulcer inhibition in all the three models. The LPO, MPO and antioxidant levels (SOD, CAT, and GSH) were significantly restored in treated groups compared to ulcer control, proving antioxidant activity of the extract. Histopathological sections showed significant decrease in mucosal ulceration, inflammatory mucosal changes and submucosal edema compared to ulcer control group. These findings indicate that ethanolic leaf extract of Mussaenda glabrata possesses antiulcer, antisecretory and cytoprotective activity and, hence, can be used in the traditional management of peptic ulcer disease.
The ethanolic extracts from the leaves of Casuarina equisetifolia showed protective effects against ethanol, indomethacin, and pylorus ligation and cold restraint stress-inducedgastric mucosal damage. The anti- ulcer effect of ethanol extract was tested against gastric lesions induced by ethanol, the experimental model related to lesion pathogenesis with production of reactive oxygen species. Reactive oxygen species are involved in the pathogenesis of ethanol-inducedgastric mucosal injury in vivo . Casuarina equisetifolia prevented the mucosal lesions induced by ethanol. The gastric mucosal protection against ethanol can be mediated through a number of mechanisms that include enhancement of the gastric mucosal defense through increase in mucus and/or bicarbonate production, reducing the volume of gastric acid secretion or by simply neutralizing the gastric acidity . Ethanol extract may either reduce the gastric acid secretion or enhance the barrier defence of the mucosal wall. Ethanol extract dose dependent inhibition in ethanolinducedgastric lesions  (Table -1).
Vehicle control, EMA in doses 200 and 400 mg/kg and ranitidine 50 mg/kg were administered orally for 7 days in their respective groups on the eighth day, experiment was performed by the standard method with some modifications as described by Gupta et al 28 . Briefly, wistar albino rats were fasted for 18 hrs and deprived of water for 12 hrs. Again, animals in group 1 received 1% w/v CMC solution, groups 2 and 3 were administered with EMA at the doses of 200 and 400 mg/kg, p.o., respectively, 1 hr before the indomethacin administration (20 mg/kg, p.o.). Group 4 was administered with the reference drug ranitidine (50 mg/kg, p.o.). The animals were sacrificed after 1 hr. Each stomach was then opened along the greater curvature, rinsed with normal saline and examined grossly. Ulcer index was determined using the following scoring system: 0=normal mucosa, 0.5=blushing, 1=spot ulcers, 1.5=haemorrhage streaks, 2= 3 mm <ulcers <5 mm and 2.5=ulcers>5 mm 29 .
respectively. Sixty minutes later, vehicle was given orally to the normal control group, and absolute ethanol was given orally to the ulcer control, positive control and experimental groups to generate gastric mucosal injury. The rats were sacrificed an hour later. The effect of oral administration of plant extract on ethanol-inducedgastric mucosal injury was studied grossly and histology. The level of lipid peroxidation, (malondialdehyde—MDA), superoxide dismutase (SOD) and gastric wall mucus were measured from gastric mucosal homogenate. The ulcer control group exhibited severe gastric mucosal injury, and this finding was also confirmed by histology of gastric mucosa which showed severe damage to the gastric mucosa with edema and leucocyte infiltration of the submucosal layer. Pre-treatment with plant extract significantly reduced the formation of ethanol-inducedgastric lesions, and gastric wall mucus was significantly preserved. The study also indicated a significant increase in SOD activity in gastric mucosal homogenate, whereas a significant decrease in MDA was observed. Acute toxicity tests did not show any signs of toxicity and mortality up to 5 g/kg. The ulcer protective effect of this plant may possibly be due to its preservation of gastric wall mucus along with increased SOD activity and reduction of oxidative stress (MDA). The extract is non-toxic, even at relatively high concentrations.
Gastroprotective effect of 50% ethanolic extract of Portulaca oleracea (POE) Portulacaceae have assessed in different gastriculcer models in rats. POE (50, 100 and 150 mg/kg body weight) was administered orally, twice daily for 5 days for prevention from ethanol (EtOH) and 10 days for prevention of acetic acid induced ulcers. POE showed dose dependent inhibition of ulcer index in ethanol and acetic-acid induced ulcers. POE prevents the oxidative damage of gastric mucosa by blocking lipid peroxidation and by significant decrease in superoxide dismutase, and increase in catalase activity. The ethanolic POE showed significant gastriculcer protective effect in doses of 50-150 mg/kg, when given twice daily for 5 days against gastric ulcers induced by ethanol (EtOH), aspirin (ASA), cold restraint stress (CRS) and pyloric ligation (PL). POE showed dose dependent decrease in ulcer index (UI) against ulcers induced by: (i) ethanol (control UI: 24.5±3.0 mm2/rat, POE% decrease 62.4 -86.1%, PB/0.05 to PB/0.001); (ii) aspirin (control UI: 14.2±1.8, POE% decrease 28.9 – 77.5%, PB/0.1 to PB/0.001); (iii) cold restraint stress (control UI: 23.2±3.1, POE% decrease 38.4 – 73.27%, PB/0.2 to PB/0.001); and (iv) pylorus ligation (control UI: 20.1±2.4, POE% decrease 36.8 -82.1%, PB/0.1 to PB/0.001). Our results show that POE possesses significant gastroprotective activity which might be due to gastric defence factors.
Notes: The microscopic appearance of gastric mucosa of the rats of the normal control (A) showed the positive Pas stain noted as a bright-magenta color to the mucus cells lining the gastric pits (black arrow). The gastric mucosa of the rats of the ulcer control pretreated with only Tween 80 (B) showed that the ethanol-induced complete depletion to the mucous layer as seen by the absence of the Pas stain. however, the pretreatment with omeprazole at 20 mg/kg (C) showed intense Pas stain noted as a bright-magenta to the mucus cells lining the gastric pits due to the carbohydrate-rich, viscous mucus they secrete (black arrow). The pretreatment with BM at 5 mg/kg (D) showed moderate expansion of a substantial continuous Pas-positive mucous gel layer that lining the entire gastric mucosal surface observed histologically as a bright- magenta-stained area lining the mucosa (black arrow). The pretreatment with BM at 10 mg/kg (E) showed intense Pas stain and increased expansion of a substantial continuous Pas-positive mucous gel layer that lining the entire gastric mucosal surface observed histologically as a bright-magenta-stained area lining the mucosa (black arrow). The pretreatment with BM at 20 mg/kg (F) showed increased expansion of a substantial continuous Pas-positive mucous gel layer that lining the entire gastric mucosal surface observed histologically as a bright-magenta-stained area lining the mucosa (black arrow) (Pas stain: ×20).
treatment of rats with CPRHE. An extensive generation of ROS and free radicals causes metabolic impairments and irreversible cell damages in the human body . As such, protecting the gastric tissue from oxidative damages can provide successful treatment approaches by natural products against ulcer formation . Super- oxide dismutase by converting the superoxide to hydro- gen peroxide has a critical role in this protecting effect . Superoxide radical anions such as ROS are gener- ated by neutrophils, which results in the reaction with cellular lipids and the production of lipid peroxides . An effective indicator of oxidative stress and mucosal injuries by ROS is malondialdehyde (MDA), which is a major metabolite of lipid peroxidation . This is the first study to show that oral administration of CPRHE could protect against gastric ulceration by elevating superoxide dismutase activity, which is reflected by decreased MDA production.
extracts studied in β‐carotene assay, displayed moderate potential of quenching linoleate free radicals (generated from linoleic acid peroxidation) and shielding of the carotenoid from bleaching. The bleaching of β‐carotene could be inhibited by antioxidants, which are capable of reducing the rate of chain reaction initiated during lipid peroxidation and transforming the reactive end product to a more stable form. 29 The extracts reduced the extent of β-carotene bleaching by neutralising the linoleate - free radical and other free radicals formed in the system. 30 Among the different extracts studied in phosphomolyptenum assay, acetone extract exhibited the maximum antioxidant activity followed by ethanol extract. This assay is based on the reduction of Mo (VI) to Mo (V) in presence of the antioxidant compounds and the subsequent formation of a green phosphate / Mo (V) complex at acidic pH, which is measured at 695 nm. Ulcers are an open sore of the skin or mucus fluid layer portrayed by sloughing of aggravated dead tissue. There are numerous sorts of ulcer, for example, mouth ulcer, throat ulcer, peptic ulcer and genital ulcer. Of these peptic ulcer is seen among numerous individuals. Gastric ulcers are situated in the stomach, portrayed by agony; ulcers are basic in more seasoned age bunch. 31 It was observed that the treatment with ethanolic extract of C. pedata var. glabra at 400 mg/kg significantly (p<0.05) reduced ulceration at higher doses (100, 200 and 400 mg/kg bw.). The test extract showed gastroprotection in a dose-dependent manner and 73.26% protection at 400 mg/kg dose level.