The antiulcer action of sophora and the active constituent in Sophora. II. The antiulcer action of vexibinol

The inhibitory effect of vexibinol, one of the flavanols found in Sophora, on gastric ulcers induced by HCl-ethanol has been reported previously. In the present study, the effect of vexibinol was examined in various experimental ulcer models in order to determine the mechanism of its antiulcer action. The results indicated that the oral administration of vexibinol at 25-50 mg/kg significantly inhibited the development of ulcers induced by HCl-ethanol, 0.6 N HCl 0.2 N NaOH, absolute ethanol and 1% NH3. In addition, an intraduodenal administration of vexibinol at 300 mg/kg significantly inhibited Shay's ulcer. Further, intraduodenal administration at 300 mg/kg significantly inhibited acid secretion caused by 2-deoxy-D-glucose. These results suggest that vexibinol has not only gastric mucosal protective action but also an inhibitory effect on the secretion of gastric acids.     

Anti-ulcer effects of Trichosanthes fruits

Anti-ulcer activities of fruits of Trichosanthes kirilowii Maximowicz var. japonica Kitamura (50% ethanolic extract, TKE) were investigated in rats. TKE, at doses of 100-1000 mg/kg, showed potent protection against experimental gastric lesions, namely, those induced by water-immersion, histamine, serotonin, HCl.ethanol, 0.6 N HCl, 0.2 N NaOH, 35% NaCl, and Shay' ulcer and acetic acid-induced gastric ulcer. At doses of 500-1000 mg/kg, TKE decreased the gastric secretion and acid output in pylorus-ligation (for 7 h), but 100 mg/kg of TKE had no influence on the gastric secretion. On the other hand, TKE exerted inhibition on the contractile responses of the isolated ileum of mouse to acetylcholine. These results suggested that TKE has an anti-ulcer effect.     

Synthesis and antiulcer activity of 4-substituted 8-[(2-benzimidazolyl)sulfinylmethyl]-1,2,3,4-tetrahydroquinoli nes and related compounds

A series of 4-substituted 8-[(2-benzimidazolyl)sulfinylmethyl]-1,2,3,4-tetrahydroquinolin es was synthesized and examined for their (H+ + K+)adenosine triphosphatase (ATPase)-inhibitory and antisecretory activities against histamine-induced gastric acid secretion in rats. Many compounds tested were potent inhibitors of (H+ + K+)ATPase. Most compounds showed antisecretory activity. The antiulcer activity against water-immersion stress-induced gastric ulcer, aspirin-induced gastric ulcer and gastric necrosis induced by hydrochloric acid also were tested in the rat. Some of these compounds, in particular, 4-(N-allyl-N-methylamino)-1-ethyl-8-[(5-fluoro-6-methoxy-2-benzimidazoly l) sulfinylmethyl]-1-ethyl-1,2,3,4-tetrahydroquinoline (XVIIx) were found to have potent activity. The structure-activity relationships are discussed.     

Effects of 2-(E-2-decenoylamino)ethyl 2-(cyclohexylethyl) sulfide on various ulcer models in rats.

The effects of 2-(E-2-decenoylamino)ethyl 2-(cyclohexylethyl) sulfide (compd. III-1a) on various experimental ulcers were investigated. The oral administration of compd. III-1a at doses ranging from 30 to 300 mg/kg inhibited the acute gastric ulcerations induced by ethanol, HCl.aspirin and indomethacin in rats. Compound III-1a significantly inhibited the water immersion stress-induced gastric ulcer at doses of 3 mg/kg, p.o. The anti-ulcer activity of plaunotol as a reference drug was equivalent on an ethanol-induced ulcer to that of compd. III-1a, but weaker on HCl.aspirin, indomethacin and stress-induced ulcers than that of compd. III-1a. On indomethacin-produced gastric antral ulcer, compd. III-1a showed the same significant inhibitory activity as spizofurone did at a dose of 100 mg/kg, p.o. Compound III-1a also inhibited hemorrhagic shock-, diethyldithiocarbamic acid (DDC)-and platelet activating factor (PAF)-induced ulcers dose-dependently. Plaunotol only showed significant inhibitory activity on PAF-induced ulcer in these three ucler models. The consecutive administration of compd. III-1a (100 mg/kg, p.o.) twice a day significantly accelerated the healing of an acetic acid-induced ulcer and that of plaunotol (200 mg/kg, p.o.) showed the same activity. Moreover, orally administered compd. III-1a at a dose of 100 mg/kg decreased the gastric acid secretion in pylorus-ligated rats. The results in the present study suggest that compd. III-1a has the dual action on ulcer formation.     

A novel class of antiulcer agents. 4-Phenyl-2-(1-piperazinyl)quinolines

The synthesis of a novel class of antiulcer agents, the substituted 4-phenyl-2-(1-piperazinyl)quinolines, and their pharmacological activities (inhibitory effects on hypothermia induced by reserpine and on gastric ulcers induced by stress or ethanol) are described. These compounds can be classified into three groups (a group predominantly effective on the stress-induced ulcer, one effective on both the stress- and ethanol-induced ulcers, and one selectively effective on the ethanol-induced ulcer), with regard to antiulcer activity. The inhibitory effect on stress-induced ulcer was found to be in close relation to the antagonism of hypothermia. The structure-activity relationships in these compounds are described. Among the compounds, 2-(4-ethyl-1-piperazinyl)-4-phenylquinoline dimaleate (9, AS-2646) showed a potent inhibition of stress-induced ulcer and gastric acid secretion, possively through action on the central nervous system, and it was selected for clinical evaluation.     

Secondary metabolites for antiulcer activity

Peptic ulcers are open sores or erosions in the lining of either the duodenum (duodenal ulcers) or the stomach (gastric ulcers). Peptic ulcer, which is mainly caused by bacterial attack or excess of acid secretion, can be cured effectively by these isolated plant compounds. In this present scenario, demand for herbal medicines are increasing due to easy availability in surrounding place at low cost. This review article is all about such isolated plant compounds such as alkaloids, flavonoids and terpenoids. Various plants have been used as folk medicine by the people of rural area, which shows significant effect against peptic ulcer. Further study should be conducted upon these herbal plants because there is possibility for minimising the adverse effect caused by the present antiulcer drugs.     

慢性胃炎、溃疡病患者血清、胃液和胃组织微量元素的测定及其临床意义

对慢性胃炎、溃疡病患者血清、胃液、胃组织中多种微量元素采用高频等离子体发射光谱法测定．结果：胃溃疡血清、胃组织钼低，Ｐ均＜０．０５；胃组织钙低，Ｐ＜０．０１．十二指肠溃疡血清、胃组织钼低，Ｐ均＜０．０５；胃组织钙高于对照组，Ｐ＜０．０１．并对健康人血清、胃液、胃组织微量元素进行测定，为科研提供了血清、胃液、胃组织微量元素的正常值。     

Pepsinogen secretion from cultured rat gastric mucosal cells

Rat gastric mucosal cells were isolated with the aid of 0.1% collagenase and Dispase. Pepsinogen secretion from these cells was stimulated by carbachol, cholecystokinin octapeptide (CCK(S)-8) and pentagastrin, but not by histamine. Attempts to obtain a sufficient number of cells using a higher concentration of Dispase resulted in disappearance of the responses to secretagogues. However, when gastric mucosal cells thus prepared were cultured for 24 h in a CO2 incubator, they were found to respond not only to carbachol, CCK(S)-8 and pentagastrin, but also to histamine, resulting in an increase in pepsinogen secretion. The secretagogue-induced pepsinogen secretion was inhibited by its antagonist in a dose-dependent manner. These results suggest that the receptor present in chief cells for pepsinogen secretion was destroyed during the isolation procedure and regenerated during culture.     

Relapse of acetic acid-induced gastric ulcer and gastric mucosal prostaglandin I2 level in rats

The healing process of acetic acid-induced gastric ulcer in rats was observed with an endoscope for 365 d after ulcer induction. The ulcers were induced by acetic acid solutions of various concentrations (2.5 (I), 5.0 (II), 10 (III) and 20% (IV); 0.05 ml). On day 3, a positive correlation was observed between the ulcer index (UI) and the concentration of acetic acid solution. On day 365, cumulative healing rates in groups I, II, III and IV amounted to 100, 100, 58.3 and 51.7%, respectively. The cumulative relapse rates in groups I, II, III and IV were 0, 13.6, 66.7 and 58.6%, respectively. Significant correlations were observed between initial UI values and cumulative healing or cumulative relapse rate. On day 365, rats were divided into two groups, a healed group and non-healed group, and the gastric mucosal prostaglandin I2 (PGI2) level was measured by bioassay. The PGI2 level around ulcers in ulcer-induced rats was higher than in normal rats, and it was higher in non-healed rats than in healed rats. Moreover, the PGI2 level was higher in those groups which showed a higher cumulative relapse rates. The above results indicated that the initial ulcer size and the PGI2 level around the ulcer might correlate to ulcer healing or exacerbation.     

Natural products in treatment of ulcerative colitis and peptic ulcer

Ulcerative colitis is an inflammatory chronic disease that affects the mucosa and submucosa of the colon and rectum. Several types of drugs are available such as aminosalicylates. Peptic ulcer disease (PUD) is a common disorder that affects millions of individuals worldwide and it can be considered one of the most important common diseases in the world. Treatment of peptic ulcers depends on using a number of synthetic drugs that reduce the rate of stomach acid secretion (Antiacids), protect the mucous tissues that line the stomach and upper portion of the small intestine (Demulcents) or to eliminate Helicobacter pylori (H. pylori). In most cases, incidence of relapses and adverse reactions is seen in the following synthetic antiulcer therapy. Accordingly, the main concern of the current article is to introduce a safe drug (or more) of natural origin, to be used for the management of gastric ulcers without side effects.A widespread search has been launched to identify new anti-ulcer therapies from natural sources. Herbs, medicinal plants, spices, vegetables and crude drug substances are considered to be a potential source to control various diseases including gastric ulcer and ulcerative colitis. In the scientific literature, a large number of medicinal plants and their secondary metabolites with potential anti-ulcer (anti-peptic ulcer and antiulcerative colitis) activities have been reported. Treatment with natural products produces promising results and fewer side effects. Our goal is to collect the published data in the last 24 years and reviews the natural products reported in the treatment of these diseases and their mechanism of action.     

Antiulcerogenic activity of borneol derivatives

Antiulcerogenic activity of borneol and its N-heterocyclic esters was investigated using indomethacin-induced gastric ulcer model. A considerable antiulcerogenic effect comparable to that shown by Omeprazole and Famotidine was found for two investigated compounds in the indomethacin-induced gastric ulcer model. Bornyl 2-piperazinoacetate, with a non-substituted piperazine moiety, showed maximum antiulcerogenic activity in the indomethacininduced gastric ulcer model and demonstrated a significant gastroprotective effect in the ethanol-induced gastric ulcer model comparable to the effect of Omeprazole.

     

Direct inhibition of pepsinogen secretion from rat gastric chief cells by somatostatin

Effects of somatostatin on pepsinogen secretion was investigated in the rat in vivo and in vitro. In the perfused rat stomach, somatostatin inhibited secretagogue-induced acid secretion in dose-dependent manner. However, effects of somatostatin on secretagogue-induced pepsinogen secretion were obscure. To clarify the effects of somatostatin on the chief cells, gastric mucosal cells were isolated by a proteolytic enzyme. Somatostatin inhibited carbachol- and cholecystokinin octapeptide-induced pepsinogen secretion from dispersed gastric mucosal cells in a dose-dependent manner. Histamine-induced pepsinogen secretion, which was recovered by culturing, was also inhibited by somatostatin. These results suggest that somatostatin inhibits secretagogue-induced pepsinogen secretion directly.     

Role of Daucus carota in Enhancing Antiulcer Profile of Pantoprazole in Experimental Animals

The carrot plant (Daucus carota) and its components are traditionally reported for the management of gastric ulcers. This study was performed to evaluate the role of carrot when administered concurrently with a conventional antiulcer treatment, pantoprazole, in alleviating gastric and duodenal ulcers in female experimental animals. The study involved standard animal models to determine the ulcer preventive effect using pylorus ligation, ethanol, and stress induced acute gastric ulcer models and duodenal ulcer models involving cysteamine. Acetic acid-induced chronic gastric ulcer and indomethacin-induced gastric ulcer models were used to evaluate the ulcer healing effect. Carrot fruit (500 mg/kg) and its co-administration with pantoprazole produced significant protection in an ethanol- and stress-induced acute gastric ulcer and cysteamine-induced duodenal ulcer. The healing of the acetic acid-induced chronic gastric ulcer was also augmented with this combination. Both total proteins and mucin contents were significantly increased in indomethacin-induced gastric ulcers. Similarly, in pylorus ligation, the pepsin content of gastric juice, total acidity, and free acidity were reduced. Overall, both ulcer preventive effects and ulcer healing properties of the pantoprazole were significantly enhanced in animals who received the co-administration of carrot fruit (500 mg/kg).     

Effect of extracts of Zingiberaceae herbs on gastric secretion in rabbits

Some of the Zingiberaceae herbs are known to be useful as stomachics. Water extracts and methanol extracts of eight such herbs were examined in intact unanesthetized rabbits for their effect on gastric secretion. Oral administration of either water extracts or methanol extracts caused a significant decrease in gastric secretion. A significant effect of these extracts appeared at 3 h after administration. The effect of water extracts on gastric secretion was very similar to that of cimetidine, with a significant decrease in acid output. The effect of the methanol extracts was primarily observed as decreased pepsin output.     

Cytoprotective Effect of Benzyl <em>N'</em>-(5-Chloro-indol-3-yl-methylidene)-hydrazinecarbodithioate Against Ethanol-Induced Gastric Mucosal Injury in Rats

Indolic compounds have attracted a lot of attention due to their interesting biological properties. The present study was performed to evaluate the subacute toxicity and anti-ulcer activity of BClHC against ethanol-induced gastric ulcers. Experimental animal groups were orally pre-treated with different doses of BClHC (50, 100, 200 and 400 mg/kg) in 10% Tween 20 solution (vehicle). Blank and ulcer control groups were pre-treated with vehicle. The positive group was orally pretreated with 20 mg/kg omeprazole. After one hour, all groups received absolute ethanol (5 mL/kg) to generate gastric mucosal injury except the blank control group which was administered the vehicle solution. After an additional hour, all rats were sacrificed, and the ulcer areas of the gastric walls determined. Grossly, the ulcer control group exhibited severe mucosal injury, whereas pre-treatment with either derivative or omeprazole resulted in significant protection of gastric mucosal injury. Flattening of gastric mucosal folds was also observed in rats pretreated with BClHC. Histological studies of the gastric wall of ulcer control group revealed severe damage of gastric mucosa, along with edema and leucocytes infiltration of the submucosal layer compared to rats pre-treated with either BClHC or omeprazole where there were marked gastric protection along with reduction or absence of edema and leucocytes infiltration of the submucosal layer. Subacute toxicity study with a higher dose of derivative (5 g/kg) did not manifest any toxicological signs in rats. In conclusions, the present finding suggests that benzyl N'-(5-chloroindol-3-ylmethylidene)hydrazinecarbodithioate promotes ulcer protection as ascertained by the comparative decreases in ulcer areas, reduction of edema and leucocytes infiltration of the submucosal layer.     

Gastroprotective Effects of Inulae Flos on HCl/Ethanol-Induced Gastric Ulcers in Rats

Inulae Flos, the flower of Inula britannica L., is used as a dietary supplement, beverage, and medicine in East Asia. In this study, we evaluated the gastroprotective effects of Inulae Flos extract (IFE) against gastric mucosal lesions induced by hydrochloric acid (HCl)/ethanol in rats and explored its potential mechanisms by measuring antioxidant enzyme activity, mucus secretion, and prostaglandin E₂ (PGE₂) levels. Pretreatment with IFE at doses of 100 and 300 mg/kg significantly inhibited gastric lesions in HCl/ethanol-treated rats. IFE increased the activities of superoxide dismutase and catalase and the levels of glutathione and PGE₂ in gastric tissues. The administration of IFE also significantly increased the gastric wall mucus contents in HCl/ethanol-induced gastric lesions. These findings suggest that IFE has gastroprotective effects against HCl/ethanol-induced gastric lesions and exerts these effects through increased antioxidant levels and gastric mucus secretion. Inulae Flos may be a promising agent for the prevention and treatment of gastritis and gastric ulcers.     

Antioxidant and Gastroprotective Activity of Suaeda fruticosa Forssk. Ex J.F.Gmel

Suaeda fruticosa Forssk. Ex J.F.Gmel is traditionally used for inflammatory and digestive disorders, as a carminative, and for diarrhea. This plant is widely distributed in Asia, Africa, and the Mediterranean region. Aqueous methanolic extract of S. fruticosa (Sf.Cr) was prepared and screened for phytoconstituents through qualitative and GC-MS analysis. Quantification of total phenolic and flavonoid contents was performed, while antioxidant capacity was determined by DPPH, CUPRAC, FRAP, and ABTS assays. The gastroprotective activity was assessed in an ethanol-induced ulcer model. Gastric secretory parameters and macroscopic ulcerated lesions were analyzed and scored for ulcer severity. After scoring, histopathology was performed, and gastric mucus contents were determined. Oral pre-treatment of Sf.Cr demonstrated significant gastroprotection. The gastric ulcer severity score and ulcer index were reduced while the %-inhibition of ulcer was increased dose-dependently. The Sf.Cr significantly elevated the pH of gastric juice, while a decrease in total acidity and gastric juice volume was observed. Histopathology demonstrated less oedema and neutrophil infiltration in gastric mucosa of rats pre-treated with the Sf.Cr in comparison to ethanol-intoxicated animals. Furthermore, the gastric mucus contents were increased as determined by alcian blue binding. Sf.Cr showed marked gastroprotective activity, which can be attributed to antioxidant, antisecretory, and cytoprotective effects.     

Effects of Pithecellobium jiringa ethanol extract against ethanol-induced gastric mucosal injuries in Sprague-Dawley rats

Current anti-gastric ulcer agents have side effects, despite the progression and expansion of advances in treatment. This study aimed to investigate the gastroprotective mechanisms of Pithecellobium jiringa ethanol extract against ethanol-induced gastric mucosal ulcers in rats. For this purpose, Sprague Dawley rats were randomly divided into five groups: Group 1 (normal control) rats were orally administered with vehicle (carboxymethyl cellulose), Group 2 (ulcer control) rats were also orally administered with vehicle. Group 3 (positive control) rats were orally administered with 20 mg/kg omeprazole, Groups 4 and 5 (experimental groups) received ethanol extract of Pithecellobium jiringa ethanol extract at a concentration of 250 and 500 mg/kg, 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-induced gastric 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-induced gastric 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.     

Studies on gastric antiulcer active agents. II. Synthesis of tetrazole alkanamides and related compounds

A series of tetrazole alkanamides was synthesized and tested for antiulcer activity against acetic acid-induced gastric ulcer in rats. These compounds were prepared by the reaction of tetrazole alkanoic acids and various amines by the mixed anhydride method or acid chloride method. Among them, 3-[(1-ethyl-5-tetrazolyl)methylthio]propionamide (IIn) was found to have the most potent activity. The structure-activity relationships are discussed.     

Potentiated effect of vagal stimulation and hormonal agents on pancreatic exocrine secretion in dogs

Chronic experiments were made on eighteen dogs with Thomas pancreatic fistula and gastric fistula. Both in chronic and acute experiments the degenerated right cervical vagus nerve was stimulated by electrical shock and the endogenous secretin and CCK was released by means of duodenal acidification (D. A.). The exogenous secretin, atropine and lidocaine were infused to analyse the interrelationship of neurohormones in the pancreatic exocrine secretion. The results were as follows. In chronic experiments the pancreatic secretory latency was shorter and volume larger than that in acute experiments induced by D. A. The difference is very significant (P less than 0.001). Both vagotomy and atropine significantly inhibited pancreatic secretion induced by D. A. (P less than 0.01). Lidocaine infused into duodenum inhibited pancreatic secretion induced by D. A. as well. When vagal stimulation was combined with D. A., either simultaneously or successively, the pancreatic secretion was increased more than the additive sum obtained by separate action of vagal stimulation and D. A. or secretin. In view of the above-mentioned facts, the author suggests that vagal impulses combined with D. A. or secretin act on the pancreatic exocrine secretion, and that the interaction of nerve and hormones appear to be mutually potentiated.