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1.  Antiulcer effect of the methanolic extract of Tamarindus indica seeds in different experimental models 
Background:
Peptic ulcer is a global health problem of the gastrointestinal tract characterized by mucosal damage secondary to pepsin and gastric acid secretion which occurs due to due to an imbalance between offensive and defensive factors.
Objective:
The present study was carried out with methanolic extract of the seed coat of Tamarindus indica Linn. to evaluate its antiulcer potential on ibuprofen, alcohol and pyloric ligation induced gastric lesions.
Materials and Methods:
Doses of 100 mg/kg & 200 mg/kg of methanolic extract wre administered orally to rats of different groups. Ranitidine at a dose of 50 mg/kg was used as a standard drug for these gastric ulcer models. The gastric content was collected and the volume was measured. The ulceration index was determined by examining the inner lining of each stomach. Furthermore, the effect was assessed by free acidity, pepsin activity, total carbohydrate (TC), protein content (PK).
Result:
The result showed that the methanolic extract of seed coats of Tamarindus indica significantly reduce the total volume of gastric juice, free and total acidity of gastric secretion (P < 0.01) in pylorus ligation induced ulcer model as is comparable with the standard drug ranitidine. There was also a significant reduction in ulcer index (P < 0.01) as compared to control group.
Conclusion:
The methanolic extracts of seed coat of Tamarindus indica can be used as a new source of antiulcer agent in animals.
doi:10.4103/0975-7406.80778
PMCID: PMC3103918  PMID: 21687352
Peptic ulcer; ranitidine; Tamarindus indica; ulcer index
2.  Cytoprotective and Antioxidant Effects of the Methanol Extract of Eremomastax Speciosa in Rats 
Background
Ethno-botanical information shows that Eremomastax speciosa is used in the traditional management of various stomach complaints including gastro-duodenal ulcers.
Materials and Methods
In this study, we tested the cytoprotective potential of the whole plant methanol extract (100–200 mg/kg, p.o), against HCl/ethanol, absolute ethanol, cold/restraint stress rats, and pylorus legated rats pre-treated with indomethacin. The effects of the extract on gastric lesion inhibition, the volume of gastric juice, gastric pH, gastric acid output, mucus production and gastric peptic activity were recorded. Oxidative stress parameters were measured in blood and gastric tissue samples obtained from the animals in all the models tested.
Results
The extract significantly (p<0.05), reduced the formation of cold/restraint ulcers by (31–60%, inhibition), completely inhibited (100%) the formation of lesions induced by HCl/ethanol at the highest dose, but was less effective against absolute ethanol (22–46% inhibition). The extract (200 mg/kg), significantly reduced lesion formation (P<0.01), gastric acidity (P<0.01), and volume of gastric secretions (P<0.05), in the indomethacin/pylorus ligation model, and did not affect the activity of pepsin in gastric juice. Blood concentrations of antioxidant enzymes (catalase, SOD and GSH), increased significantly and MDA concentrations decreased in all models tested.
Conclusion
Cytoprotection by E. speciosa methanol extract was attributed to its ability to reduce acid secretion, and to enhance mucosal defence and in vivo antioxidant status.
PMCID: PMC3957260  PMID: 24653572
Eremomastax speciosa; cytoprotection; gastric ulcers; antioxidant status
3.  Serum carbenoxolone in patients with gastric and duodenal ulcer: Absorption, efficacy and side-effects. 
Gut  1978;19(4):330-335.
The absorption of carbenoxolone sodium has been studied in 15 patients with gastric ulcer and eight patients with duodenal ulcer treated for four weeks. Blood levels of carbenoxolone showed a log distribution, varied markedly between patients, and were significantly higher after Biogastrone tablets (300 mg/day) than after Duogastrone capsules (200 mg/day). Serum carbenoxolone levels were similar in patients taking Biogastrone tablets before or after meals, and in patients taking Biogastrone tablets or Duogastrone capsules with or without antacids following chronic administration. Serum carbenoxolone levels were similar in patients whose gastric ulcers had or had not healed after four weeks' treatment. Serum carbenoxolone was significantly higher in patients who developed oedema, and was significantly correlated with age and with fall in plasma potassium. Carbenoxolone may exert its metabolic effects systemically, but its ulcer-healing effects topically; additional studies are needed to test this hypothesis.
PMCID: PMC1411939  PMID: 648939
4.  pH, healing rate, and symptom relief in patients with GERD. 
Gastroesophageal reflux symptoms are common and occur in all of us from time to time. In others, reflux may be associated with ulcerative esophagitis. The symptoms may be aggravated by large meals, coffee, smoking and position. Physiological and pathological reflux can be separated by the frequency and duration of the exposure of the lower esophagus to acid. Pathological reflux results in symptoms and also esophagitis and ulceration in some patients. Although gastroesophageal reflux disease (GERD) is considered to result from a disorder of motility in the esophagus, gastric acid and peptic activity are deemed pivotal to the initiation and continuation of the esophageal damage and the development of symptoms. Acid exposure in the esophagus is normally less than 4 percent of the 24 hours with a pH below 4. An increase over 4 percent of the time with a pH less than 4 is considered pathological. Hence, antisecretory drugs have become the principle approach to the treatment of reflux symptoms and esophagitis since they reduce the acidity, of gastric juice and the activity of pepsin. Importantly, they also reduce the volume of gastric juice available for reflux into the esophagus. There is a clear relationship between the degree and duration of acid suppression and the relief of heartburn and healing of esophagitis. Pharmacodynamic studies with different dose regimens of the H2-receptor antagonists and the proton pump inhibitors show a difference in the degree and duration of the antisecretory effect, and this correlates closely with the results of clinical trials with respect to the healing of esophagitis and the relief of symptoms. Proton pump inhibitors achieve healing rates by week four, which are not achieved by H2-receptor antagonists even after 12 weeks of treatment. The advantage of proton pump inhibitors over H2-receptor antagonists is due to the greater degree, longer duration of effect and more complete inhibition of acid secretion that maintains intragastric pH above 4 for a maximal duration. Although there is no significant difference between proton pump inhibitors with respect to healing of esophagitis, symptom relief occurs earlier with lansoprazole than omeprazole, and this is probably due to the greater oral bioavailability and faster onset of action of lansoprazole when compared to omeprazole.
PMCID: PMC2579003  PMID: 10780580
5.  Mucus degradation by pepsin: comparison of mucolytic activity of human pepsin 1 and pepsin 3: implications in peptic ulceration. 
Gut  1986;27(3):243-248.
The ability to digest mucus, mucolytic activity of isolated pepsins and samples of human gastric juice has been assayed by measuring the fall in viscosity when incubated with purified pig gastric mucus glycoprotein. Pure human pepsin 1, the peptic ulcer associated pepsin, digested gastric mucus glycoprotein at a faster rate than did pure human pepsin 3 (the principal human pepsin), or the equivalent pig pepsin (pepsin A). At pH 2.0 pepsin 1 had twice the mucolytic activity of pepsin 3. Above pH 3.8 this difference became more marked and whereas pepsin 1 caused substantial mucolysis up to and including pH 5.1, pepsin 3 had minimal activity. At pH 4.0 pepsin 1 had six times the mucolytic activity of pepsin 3. Gastric juices from patients with duodenal ulcer each exhibited substantial mucolytic activity between pH 2 to 5, similar to that of pepsin 1. In contrast, gastric juice from non-symptomatic volunteers exhibited little mucolytic activity above pH 4. Analysis of the mucus glycoprotein by gel filtration showed that an increase in lower molecular weight, pepsin degraded, glycoprotein was associated with the fall in mucus viscosity for all enzyme preparations. These results showed that pepsin 1 can digest the mucus more effectively than pepsin 3 and at higher pH values. The raised concentrations of pepsin 1 in the juice of peptic ulcer patients may thus promote the ulcerative process by increased erosion of the mucus barrier under conditions likely to pertain in the duodenal bulb as well as the stomach.
PMCID: PMC1433406  PMID: 3084340
6.  The evaluation of anti-ulcerogenic effect of rhizome starch of two source plants of Tugaksheeree (Curcuma angustifolia Roxb. and Maranta arundinacea Linn.) on pyloric ligated rats 
Ayu  2014;35(2):191-197.
Background:
In the present era, because of the life-style, the disorders such as hyperacidity and gastric ulcers are found very frequently. Satwa (starch) obtained from the rhizomes of two plants namely Curcuma angustifolia Roxb. and Maranta arundinacea Linn. are used in folklore practice for the treatment of above complaints under the name Tugaksheeree.
Aim:
To compare the anti-ulcerogenic activity of the above two drugs in pyloric ligation induced gastric ulcer in albino rats.
Materials and Methods:
A total of 18 Wistar strain albino rats of both sexes grouped into three groups. Group C served as pyloric ligated control group, Group I received starch of C. angustifolia suspension and Group II received starch of M. arundinacea for seven days. On 8th day pylorus was ligated. After ligation the animals were deprived of food and water and sacrificed at the end of 14 h. The collected gastric contents were used for biochemical estimation and ulcer index was calculated from excised stomach.
Results:
Both the test drugs showed statistically significant decrease in the volume, increase in the pH, reduced the free acidity of gastric juice and decreased the peptic activity. The starch of C. angustifolia reduced a total acidity non-significantly while M. arundinacea reduced it significantly. Among the two drugs the M. arundinacea has effectively reduced the peptic activity, which is statistically significant. M. arundinacea shown statistically significant increase of total carbohydrates.
Conclusion:
Both the test drugs proved anti-ulcer activity and prevents the chance of gastric ulcer. Among these two M. arundinacea is more effective.
doi:10.4103/0974-8520.146251
PMCID: PMC4279328  PMID: 25558167
Curcuma angustifolia; gastric ulcer; Maranta arundinacea; pyloric ligation; starch; Tugaksheeree
7.  Clinical trial of a new carbenoxolone analogue (BX24), zinc sulphate, and vitamin A in the treatment of gastric ulcer 
Gut  1972;13(6):459-463.
The effects of a new carbenoxolone analogue (BX24), zinc sulphate, and vitamin A on the healing of gastric ulcer have been assessed in a multifactorial clinical trial conducted in out-patients treated for four weeks.
Forty-eight patients completed the trial. Three groups of eight patients were given respectively 300, 600, and 1 200 mg of BX24 daily and were compared with 24 patients who were given 300 mg of carbenoxolone sodium daily. The size of the ulcer niche was reduced on average by 14·6% in the eight patients given BX24 300 mg daily, by 47·6% in the patients given 600 mg daily, and by 51·0% in the patients given 1 200 mg daily. In the patients given carbenoxolone the size of the niche was reduced by 68·9%. These results were compared with those obtained previously with carbenoxolone and inert tablets and it was concluded that BX24 is without clinically useful effect in the doses used.
Eleven of the 24 patients (46%) treated with carbenoxolone sodium developed side effects due to fluid retention and electrolyte disturbances. None of the patients given BX24 experienced such effects.
In addition to carbenoxolone or BX24, 24 patients were given zinc sulphate, 660 mg daily, and in 24 patients these tablets were withheld. Among the patients given carbenoxolone the reduction in the size of the niche was much the same irrespective of whether or not the patients received zinc sulphate. Among the 12 patients given BX24 with zinc sulphate the ulcer healed completely in four and, on average, the size of the niche was reduced by 53·5%, compared with 21·9% in the 12 patients given BX24 alone. This difference is not statistically significant but the possibility of a beneficial effect from zinc is not excluded. No side effects attributable to zinc were observed.
Twenty-four patients were also given vitamin A, 50 000 units daily, and in 24 patients the vitamin was withheld. No evidence was obtained to suggest that vitamin A had any beneficial effect on the healing of gastric ulcer.
PMCID: PMC1412200  PMID: 4557308
8.  Metabolic Studies, Aldosterone Secretion Rate, and Plasma Renin after Carbenoxolone Sodium 
British Medical Journal  1969;2(5660):793-795.
A formal metabolic study of carbenoxolone sodium (Biogastrone) 300 mg./day has been performed for 17 days on a woman with gastric ulcer who in a previous 21-day trial, on a 52-mEq sodium diet, showed weight gain, retention, and rise in plasma sodium and chloride concentrations, as well as hypokalaemia without change in potassium balance. In the present trial sodium intake was restricted to 26 mEq/day; while plasma electrolyte changes of lesser degree still occurred, there was no retention of water, sodium, or chloride. Aldosterone secretion in the control period was 202 μg./24 hours, and fell to 74 μg./24 hours after carbenoxolone, but plasma renin was unchanged.
These results suggest that the mineralocorticoid effects of carbenoxolone (and presumably of liquorice and its other derivatives) are due to an intrinsic aldosterone-like action, and that, with sodium deprivation, aldosterone secretion is suppressed by a mechanism which is not renin-mediated—possibly hypokalaemia.
PMCID: PMC1983758  PMID: 5784614
9.  Gastric epithelial cell turnover, mucus production, and healing of gastric ulcers with carbenoxolone. 
Gut  1977;18(10):817-820.
Nineteen healthy subjects were studied and 17 patients with gastric ulcer before and after ulcer healing with carbenoxolone. Gastric deoxytibonucleic acid (DNA) loss was measured as an index of epithelial cell turnover, and N-acetylneuraminic acid (NANA) content of gastric juice as an index of mucus secretion. In normal subjects there was a negative correlation (p less that 0-025) between gastric DNA loss and NANA secretion; the lower the cell turnover the higher the NANA production. In gastric ulcer patients DNA loss or turnover was significantly (p less than 0-01) higher than normal, and fell significantly (p less than 0-01) after four weeks' treatment with carbenoxolone when 16 of the 17 ulcers had healed. At the same time NANA output increased significantly (p less than 0-01). It is suggested that patients with gastric ulcer lose cells at a high rate, a state of affairs which is returned towards normal by carbenoxolone, thus allowing the epithelial cells to mature within the mucosa and produce more mucus.
PMCID: PMC1411689  PMID: 590840
10.  Gastroprotective and Ulcer Healing Effects of Essential Oil of Hyptis martiusii Benth. (Lamiaceae) 
PLoS ONE  2014;9(1):e84400.
Hyptis martiusii Benth. is an aromatic plant found in abundance in northeastern Brazil that is used in ethnomedicine to treat gastric disorders. The aim of this study was to elucidate the mechanisms of action involved in the gastroprotection of the essential oil of Hyptis martiusii (EOHM) and to evaluate its healing capacity. Wistar rats were exposed to different protocols and subsequently were treated with 1% Tween-80 aqueous solution (negative control), pantoprazole, carbenoxolone, N-acetylcysteine (depending on the specificity of each model) or EOHM. The antisecretory activity (basal or stimulated) was determined using the pyloric ligature method. The gastroprotective action of nitric oxide and sulphydryl groups (–SH groups), as well as the quantification of adherent mucus and the levels of malondialdehyde and –SH groups in gastric mucosa, were evaluated using ethanol-induced gastric ulcer model. The healing ability was evaluated using the acetic acid-induced gastric ulcer model and histological and immunohistochemical analysis (HE, PAS and PCNA). EOHM (400 mg/kg) reduced the volume and acidity of gastric secretion stimulated by histamine and pentagastrin. The gastroprotective effect of EOHM involves the participation of endogenous sulfhydryl groups. EOHM increased mucus production (54.8%), reduced levels of MDA (72.5%) and prevented the depletion of –SH groups (73.8%) in the gastric mucosa. The treatment with EOHM reduced in 70.3% the gastric lesion area, promoting significant regeneration of the gastric mucosa, as confirmed by histological analysis and analysis of proliferating cell nuclear antigen. The results show that gastroprotective effect of EOHM is mediated by cytoprotective and antioxidant mechanisms and by their antisecretory activity, and suggest that the essential oil of Hyptis martiusii is a promising candidate for the treatment of gastric ulcers.
doi:10.1371/journal.pone.0084400
PMCID: PMC3893125  PMID: 24454726
11.  Pepsin 1 secretion in chronic peptic ulceration. 
Gut  1980;21(9):766-771.
In patients with peptic ulceration, both vagal stimulation by insulin hypoglycaemia and stimulation by pentagastrin cause pepsin 1 to be secreted into gastric juice. There is a secretory threshold for pepsin 1, below which only pepsins 3 and 5 are secreted. Pepsin 1 accounts for an increasing proportion of the total peptic activity/ml of gastric juice as the total activity increases. Higher concentrations of pepsin 1 in the basal gastric secretion occurred significantly more frequently in patients with duodenal ulcer than with gastric ulcer. In these patients there may be an increased 'background' secretory drive.
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PMCID: PMC1419519  PMID: 6776016
12.  Pepsin 5 in gastric juice: determination and relationship to the alkali-stable peptic activity. 
Gut  1979;20(11):977-982.
Pure human pepsins 1 and 3 are inactivated by incubation at pH 7.1-7.3 for 30 minutes, losing 90% or more of activity. Pepsin 5 is alkali-stable, retaining 100% of activity. Mixtures of pure pepsins 1 and/or 3 with pepsin 5 were found to have greater alkali-stable activity than predicted. Two published methods for determining the alkali-stable fraction of the peptic activity of gastric juice gave, respectively, in our hands values of 45.4-80.0% and 27.5-43.9% of the total activity. These values seemed too high to be attributable only to pepsin 5 in gastric juice, as agar gel electrophoresis shows pepsin 3 to have the principal activity. Electrophoretograms of alkaline incubated gastric juice revealed that large amounts of pepsin 3 retained activity as well as pepsin 5, and a proteolytic zone "4" appeared between them. Alkali inactivation thus does not allow the estimation of pepsin 5 individually in gastric juice. Pepstatin, at a final concentration of 100 to 170 pmol/ml, may be used to estimate pepsin 5 in gastric juice and gave values of 18.0 to 27.6% of the total peptic activity. Pepsin 5, in gastric juice and in mixtures of pepsins, appears to protect pepsin 3 from alkaline-inactivation, and to a lesser extent from pepstatin inhibition.
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PMCID: PMC1412680  PMID: 43273
13.  A potential of some medicinal plants as an antiulcer agents 
Pharmacognosy Reviews  2010;4(8):136-146.
Peptic ulcers are a broad term that includes ulcers of digestive tract in the stomach or the duodenum. The formation of peptic ulcers depends on the presence of acid and peptic activity in gastric juice plus a breakdown in mucosal defenses. There are two major factors that can disrupt the mucosal resistance to injury: non-steroidal antiinflammatory drugs (NSAIDs) example, aspirin and Helicobacter pylori infection. Numerous natural products have been evaluated as therapeutics for the treatment of a variety of diseases, including peptic ulcer. There has been considerable pharmacological investigation into the antiulcer activity of some compounds. In this work, we shall review the literature on different medicinal plant and alkaloids with antiulcer activity. This article reviews the antiacid/anti-peptic, gastroprotective and/or antiulcer properties of the most commonly employed herbal medicines and their identified active constituents. The experimental parameters used for antiulcer activity were cold restraint stress-induced ulcer model, Diclofenac-induced ulcer model in rats, (HCl–ethanol)-induced ulcer in mice and water immersion stress-induced ulcer in rats. The ideal aims of treatment of peptic ulcer disease are to relieve pain, heal the ulcer and delay ulcer recurrence. About 70% of patients with peptic ulcer disease are infected by Helicobacter pylori and eradication of this microorganism seems to be curative for this disease. This article reviews drugs derived from medicinal plant more commonly used in the world for peptic ulcer and, if reported, the antiulcer activity. This article will be concerned only with the antiulcer and gastro-protective effects.
doi:10.4103/0973-7847.70906
PMCID: PMC3249913  PMID: 22228953
Alkaloids; antiulcer activity; flavonoids; peptic ulcer; saponin; tannins
14.  Comparative Study of Proton Pump Inhibitors on Dexamethasone Plus Pylorus Ligation Induced Ulcer Model in Rats 
The present study was designed to compare ulcer protective effect of proton pump inhibitors viz. omeprazole, rabeprazole and lansoprazole against dexamethasone plus pylorus ligation induced ulcer model. Dexamethasone (5 mg/kg) was used as an ulcerogen. Dexamethasone suspended in 1% CMC in water was given orally to all the rats 15 min after the pylorus ligation. Omeprazole (20 mg/kg), rabeprazole (20 mg/kg), and lansoprazole (20 mg/kg) were administered by oral route 30 min prior to ligation was used for ulcer protective studies, gastric secretion and mucosal studies. Effects of proton pump inhibitors were determined by the evaluation of various biochemical parameters such as ulcer index, free and total acidity, gastric pH, mucin, pepsin and total proteins. Oral administration of proton pump inhibitors showed significant reduction in gastric acid secretion and ulcer protective activity against dexamethasone plus pylorus ligation induced ulcer model. The % protection of omeprazole, rabeprazole and lansoprazole was 84.04, 89.36 and 79.78, respectively. Rabeprazole significantly inhibited the acid-pepsin secretion and increased the gastric mucin secretion. The observations made in the present study suggest that rabeprazole is the most effective gastric antisecretory and ulcer healing agent as compared to omeprazole and lansoprazole.
doi:10.4103/0250-474X.70486
PMCID: PMC3003173  PMID: 21188049
Dexamethasone; PPIs; mucosal offensive and defense factors
15.  Evaluation on the Pharmacological Effect of Traditional Chinese Medicine SiJunZiTang on Stress-Induced Peptic Ulcers 
Purpose. To explore the effects of SiJunZiTang (SJZT) on central neurotransmitters and the inhibition of HCl hypersecretion, along with the role of the vagus nerve. From this, the effects of SJZT and its constituent ingredients on inhibiting stress-induced peptic ulcers will be determined. Methods. Methods used to determine SJZT's effectiveness included (1) measuring the antipeptic ulcer effects of varying combinations of the constituents of SJZT; (2) evaluations of monoamine (MA) level in the brain; and (3) measuring the effects of longer-term SJZT treatment. Results. Comparing the control and experimental groups where the rats' vagus nerves were not cut after taking SJZT orally (500 mg/kg and 1000 mg/kg), the volume of enterogastric juice, free HCl and total acidity all reduce dose-dependently. The group administered SJZT at 1000 mg/kg showed significant reductions (P < 0.05). For the experimental groups where the vagus nerves were cut, a comparison with the control group suggests that the group receiving SJZT (500 mg/kg) orally for 21 days demonstrated a cure rate of 34.53%. Conclusion. The results display a correlation between the therapeutic effects of SJZT on stress-induced peptic ulcers and central neurotransmitter levels. Further to this, SJZT can inhibit the hypersecretion of HCl in the stomach, thus inhibiting stress-induced peptic ulcers.
doi:10.1155/2013/186076
PMCID: PMC3694386  PMID: 23840247
16.  Effect of Helicobacter pylori and its eradication on gastric juice ascorbic acid. 
Gut  1994;35(3):317-322.
The presence of ascorbic acid in gastric juice may protect against gastric carcinoma and peptic ulceration. This study examined the effect of Helicobacter pylori (H pylori) on the secretion of ascorbic acid into gastric juice by measuring fasting plasma and gastric juice ascorbic acid concentrations in patients with and without the infection and also before and after its eradication. Gastric juice ascorbic acid concentrations in 19 H pylori positive patients were significantly lower (median 2.8, range 0-28.8 micrograms/ml) than those in 10 H pylori negative controls (median 17.8, range 5.6-155.4 micrograms/ml) (p < 0.0005) despite similar plasma ascorbic acid concentrations in both groups. The median gastric juice:plasma ascorbic acid ratio in the H pylori positive patients was only 1.16 (range 0.02-6.67), compared with a median ratio of 4.87 (range 0.76-21.33) in H pylori negative controls (p < 0.01). In the patients with H pylori infection there was a significant negative correlation between the severity of the antral polymorphonuclear infiltrate and gastric juice ascorbic acid concentrations (correlation coefficient -0.52, p = 0.02). After eradication of H pylori in 11 patients, gastric juice ascorbic acid concentrations rose from 2.4 (0-12.8 micrograms/ml) to 11.2 (0-50 micrograms/ml) (p = 0.01). The median gastric juice: plasma ascorbic acid ratio also increased from 1.33 (0.05-6.67) to 2.89 (0.01-166) (p = 0.01). In conclusion, the high gastric juice:plasma ascorbic acid ratio in H pylori negative subjects shows active secretion of ascorbic acid into gastric juice. Secondly, H pylori infection causes a reversible lowering of gastric juice ascorbic acid concentrations, which may predispose to gastric carcinoma and peptic ulceration.
PMCID: PMC1374582  PMID: 8150339
17.  Gastroprotective Effect of Oxalis corniculata (Whole Plant) on Experimentally Induced Gastric Ulceration in Wistar Rats 
The objective of the present study was to investigate the antiulcer activity of methanol extract of Oxalis corniculata (whole plant) using pylorus ligation and indomethacin-induced gastric ulceration in Wistar rats. The extract was preliminary evaluated for acute oral toxicity test using Organisation for Economic Co-operation and Development guidelines 423. Further, it was studied for antiulcer potential at the dose levels of 125, 250 and 500 mg/kg. Ranitidine was used as a standard drug (100 mg/kg). Acid secretory parameters like gastric volume, pH, total acidity and free acidity were measured in pylorus ligation model, whereas numbers of ulcers, ulcers score and ulcer index was measured in pylorus ligated and indomethacin treated rats. Pretreatment of test extract significantly (p<0.05) decreased the gastric volume, total acidity, free acidity and increase in the pH of the gastric fluid in pylorus-ligated rats. It also showed significant (p<0.05) decrease in number of ulcers, ulcers score and ulcer index in pylorus ligated and indomethacin treated rats. Results of the study suggest that, the methanol extract of Oxalis corniculata possesses significant antisecretory and antiulcer effects and justify the traditional usage of this herb to treat peptic ulcers.
doi:10.4103/0250-474X.102543
PMCID: PMC3507345  PMID: 23204622
Antiulcer; indomethacin; Oxalis corniculata; pylorus ligation; ranitidine
18.  Clot lysis by gastric juice: an in vitro study. 
Gut  1989;30(12):1704-1707.
Gastric juice from patients with peptic ulcer disease and from patients with no upper gastrointestinal abnormality was studied in order to assess its effect on a formed fibrin clot. In both groups of patients gastric juice caused a marked increase in fibrinolysis as evidenced by a shortening of the euglobulin clot lysis time. This plasmin mediated fibrinolytic activity was found to be heat labile and only present in an acid environment. Addition of tranexamic acid or sucralfate to gastric juice almost completely reversed this effect, whereas pepstatin was only partially effective. It is probable that acid dependent proteases other than pepsin are responsible for the marked fibrinolysis. The ulcer healing agent sucralfate might be useful in those patients at risk of bleeding or rebleeding from active peptic ulcer disease.
PMCID: PMC1434462  PMID: 2612985
19.  RAPID HEALING OF PEPTIC ULCERS IN PATIENTS RECEIVING FRESH CABBAGE JUICE 
California Medicine  1949;70(1):10-15.
Thirteen patients with peptic ulcer were treated with fresh cabbage juice, which, experiments have indicated, contains an antipeptic ulcer factor. This factor (vitamin U) prevents the development of histamin-induced peptic ulcers in guinea pigs.
The average crater healing time for seven of these patients who had duodenal ulcer was only 10.4 days, while the average time as reported in the literature, in 62 patients treated by standard therapy, was 37 days.
The average crater healing time for six patients with gastric ulcer treated with cabbage juice was only 7.3 days, compared with 42 days, as reported in the literature, for six patients treated by standard therapy.
The rapid healing of peptic ulcers observed radiologically and gastroscopically in 13 patients treated with fresh cabbage juice indicates that the anti-peptic ulcer dietary factor may play an important role in the genesis of peptic ulcer in man.
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PMCID: PMC1643665  PMID: 18104715
20.  Cigarette smoking, chronic peptic ulceration, and pepsin 1 secretion. 
Gut  1979;20(11):971-976.
The relationship between the secretion of pepsin 1 (the most electronegative of the pepsins), and the smoking habits of 219 patients has been investigated. Significantly more cigarette smokers with peptic ulceration (72.5%) secreted pepsin 1 in greater than trace amounts after pentagastrin or histamine than did non-smokers with ulceration (51.2%). Differences of a similar order were found for men with duodenal ulcer, women with duodenal ulcer, and all patients with gastric ulcer, but the difference was statistically significant only for men with duodenal ulcer. Significantly more patients with peptic ulcer smoking six to 15 cigarettes/day secreted moderate or high concentrations of pepsin 1 than did heavier smokers or non-smokers. There was no significant association between cigarette smoking and pepsin 1 secretion among 74 patients without ulceration. Maximal acid output was not significantly related to smoking in any group studied. The findings add to the increasing body of evidence linking pepsins and pepsin 1 with the pathogenesis of peptic ulceration.
PMCID: PMC1412681  PMID: 118897
21.  The Gastroprotective Role of Acanthus ilicifolius – A Study to Unravel the Underlying Mechanism of Anti-Ulcer Activity 
Scientia Pharmaceutica  2012;80(3):701-717.
Acanthus ilicifolius (Acanthaceae), a mangrove medicinal plant, is widely used by the local inhabitants of the Sundarbans (India) to treat a variety of diseases. As a part of our continued search for novel bioactive products from mangrove medicinal plants, we were able to document the anti-inflammatory effects of this plant. In the present study, we have performed a detailed evaluation of the gastroprotective activity of the methanolic extract of Acanthus ilicifolius using different models of gastric ulceration. Unlike the conventional non-steroidal anti-inflammatory drugs, a methanolic extract of Acanthus ilicifolius leaves (MEAL) possessing significant anti-inflammatory properties, as revealed from our previous studies displayed in rats in dosages of 200 mg and 400 mg/kg BW after intraperitoneal administration, showed significant protective activity (anti-ulcer activity) against the gastric lesions induced by aspirin, indomethacin, stress, ethanol, and pylorus ligation. In pylorus-ligated rats, administration of Methanolic extract of Acanthus ilicifolius leaves (MEAL) significantly decreased gastric volume, acidity, and peptic activity. Moreover, pre-treatment with MEAL significantly restored the levels of reduced glutathione (GSH) and the antioxidant enzyme superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPX), along with significant inhibition of both lipid peroxidation and myeloperoxidase (MPO) activity in pylorus-ligated animals. Ulceration induced with ethanol was significantly inhibited with MEAL, and the extract also resulted in the reduction of both lipid peroxidation and myeloperoxidase activity. Furthermore, in this experimental model, administration of MEAL improved the activities of SOD, CAT, GSH, and GPX. A similar pattern of action was also noticed in cold-restraint stress-induced (CRS) ulceration, where MEAL pre-treatment inhibited CRS-induced ulceration, improved the status of antioxidant enzymes, and also reduced the level of lipid peroxides. These results suggest that extracts of the leaves of Acanthus ilicifolius may exhibit anti-ulcer activities additional to the anti-inflammatory properties.
doi:10.3797/scipharm.1108-11
PMCID: PMC3447604  PMID: 23008816
Acanthus ilicifolius; Sundarban mangroves; Ulcer protection; Dual inhibitor
22.  Seasonal changes in gastric mucosal factors associated with peptic ulcer bleeding 
A close association has been established between climate and peptic ulcer bleeding (PUB). The incidence of PUB in cold climates is significantly higher than that in hot climates. In this study, gastric mucosal damage and its barrier function (through associated barrier factors) in extreme climate conditions were examined to investigate the pathogenesis of PUB in extreme cold climates. Gastric juice and biopsy specimens were collected from 176 patients with peptic ulcer. Conventional hematoxylin and eosin staining was used to exclude malignant ulcers. Helicobacter pylori infections were detected by modified Giemsa staining. pH values of the gastric juice samples were obtained on-site by precise pH dipstick readings. The protein expression levels of heat shock protein (HSP) 70, occludin, nitric oxide synthase (NOS), epidermal growth factor (EGF) and EGF receptor (EGFR) in the gastric mucosa were detected by immunohistochemistry. No significant differences were identified between the high and low bleeding risk groups in the rates of H. pylori infection and the pH values of the gastric juices in the extreme hot or cold climates. Furthermore, no statistically significant differences were identified in the protein expression levels of occludin, NOS, EGF and EGFR between the high and low bleeding risk groups. In the extreme cold climate, the expression of HSP70 and the mucus thickness of the gastric antrum in the high bleeding risk group were significantly lower than those in the low bleeding risk group. The protein expression levels of occludin, HSP70, NOS and EGFR in the extreme cold climate were significantly lower than those in the extreme hot climate, whereas the gastric acid secretion was significantly higher in the extreme cold climate than that in the extreme hot climate. In conclusion, low expression of HSP70 in the gastric mucosa and reduced gastric mucus thickness may play key roles in the mechanism of PUB in extreme cold climates. The significant decrease in barrier factors and increase in damage in extreme cold climates may be associated with the seasonal pattern of peptic ulcers.
doi:10.3892/etm.2014.2080
PMCID: PMC4247295  PMID: 25452787
peptic ulcer bleeding; pathogenesis; climate
23.  Assay of gastricsin and individual pepsins in human gastric juice. 
Journal of Clinical Pathology  1993;46(3):254-258.
AIMS: To develop and validate an analytical procedure for the quantitation of pepsins and gastricsin in human gastric juice and to assess its potential in a controlled gastric secretory study. METHODS: High performance ion-exchange chromatography was used to separate human pepsin 1, 3a, 3b, 3c and gastricsin from gastric juice. Computed chromatographic areas for each enzyme were quantified by relation to a known amount of a secondary standard porcine pepsin. The assay procedure was validated by recovery and analytical precision studies. Gastric secretions after pentagastrin and insulin stimulation from 10 patients with portal hypertension were used to assess the potential of the analytical procedure. RESULTS: The assay precision varied from 1.5 to 9.0% within batch and 7.5 to 18.1% between batch, with about 100% recoveries of porcine pepsin A from human gastric juice over the assay range 0.025-0.5 mg/ml. A fourfold increase in combined pepsin and gastricsin concentration was observed following pentagastrin and insulin stimulation. The mean percentage content of pepsins 3a, 3b, 3c, and 1 in non-stimulated gastric juice were 4%, 72%, 12% and 1.4%, respectively, and did not change significantly after gastric stimulation. An approximate doubling of the percentage of gastricsin (10% to 20%) relative to the pepsins was observed, however, after both insulin and pentagastrin stimulation. CONCLUSIONS: This procedure for quantifying individual human pepsins and gastricsin in gastric juice is simple and reliable. It may be of considerable importance in determining the mechanisms involved in the control and secretion of these digestive enzymes in man, including the effect of anti-ulcer drugs and our understanding of the pathophysiology of peptic ulcer disease.
PMCID: PMC501181  PMID: 8463419
24.  A Review on Antiulcer Activity of Few Indian Medicinal Plants 
Ulcer is a common gastrointestinal disorder which is seen among many people. It is basically an inflamed break in the skin or the mucus membrane lining the alimentary tract. Ulceration occurs when there is a disturbance of the normal equilibrium caused by either enhanced aggression or diminished mucosal resistance. It may be due to the regular usage of drugs, irregular food habits, stress, and so forth. Peptic ulcers are a broad term that includes ulcers of digestive tract in the stomach or the duodenum. The formation of peptic ulcers depends on the presence of acid and peptic activity in gastric juice plus a breakdown in mucosal defenses. A number of synthetic drugs are available to treat ulcers. But these drugs are expensive and are likely to produce more side effects when compared to herbal medicines. The literature revealed that many medicinal plants and polyherbal formulations are used for the treatment of ulcer by various ayurvedic doctors and traditional medicinal practitioners. The ideal aims of treatment of peptic ulcer disease are to relieve pain, heal the ulcer, and delay ulcer recurrence. In this review attempts have been made to know about some medicinal plants which may be used in ayurvedic as well as modern science for the treatment or prevention of peptic ulcer.
doi:10.1155/2014/519590
PMCID: PMC4058214  PMID: 24971094
25.  PA01.46. Gastro protective effect of normacid powder, an herbal formulation on experimental induced ulcer in mices 
Ancient Science of Life  2012;32(Suppl 1):S96.
Purpose:
Present study was carried out to investigate antiulcer activity of Normacid powder in diclofenac and pylorus ligated induced ulceration in the albino mices.
Method:
Preliminary normacid powder was subjected to the acute oral toxicity study according to the OECD guideline no. 425. Based on which, two dose levels i.e. 250 and 500 mg/kg were selected for the further study. Various parameters were studied viz. gastric juice volume, pH, total acidity, free acidity, ulcer index, percentage inhibition, anti oxidants parameter, mucin level and mucosal nitrate level of ulceration was determined for diclofenac and pylorus induced ulcer model. Ranitidine at 20 mg/kg was used as the standard drug.
Result:
Pre-treatment of normacid powder showed significant (P<0.001) decrease in the gastric volume, total acidity and free acidity. However, pH of the gastric juice was significantly (P<0.001) increased only at higher dose, 500 mg/kg. It showed also significant (P<0.001) decrease in number of ulcers and ulcer score index in diclofenac and pylorus ligation induced ulceration models. The increase in the level of superoxide dismutase, catalase, reduced glutathione and decrease in lipid peroxidation in both the models showed the antioxidant activity of the formulation. Also increase in mucin and mucosal nitrate level in both models showed the cytoprotective activity of the formulation. Normacid powder possesses significant antiulcer properties in a dose dependent manner.
Conclusion:
In conclusion the antiulcer properties of the normacid powder may be due to the modulation of defensive factors, improvement in gastric cytoprotection and due to antioxidant property.
PMCID: PMC3800979

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