Gastroprotective effect of cardamom, Elettaria cardamomum Maton. fruits in rats

Cardamom, the fruits of Elettaria cardamomum Maton. (Zingiberaceae) commonly known as "Heel khurd" is used in Unani system of medicine to treat gastrointestinal disorders. A crude methanolic extract (TM), essential oil (EO), petroleum ether soluble (PS) and insoluble (PI) fractions of methanolic extract, were studied in rats at doses of 100-500, 12.5-50, 12.5-150 and 450 mg/kg, respectively for their ability to inhibit the gastric lesions induced by aspirin, ethanol and pylorous ligature. In addition their effects on wall mucus and gastric acid output were recorded. All fractions (TM, EO, PS, PI) significantly inhibited gastric lesions induced by ethanol and aspirin but not those induced by pylorus ligation. TM proved to be active reducing lesions by about 70% in the EtOH-induced ulcer model at 500 mg/kg. The PS fraction reduced the lesions by 50% at 50 and 100mg/kg (no dose response was observed) with similar effect than the PI fraction at 450 mg/kg. In the aspirin-induced gastric ulcer, the best gastroprotective effect was found in the PS fraction, which inhibited lesions by nearly 100% at 12.5mg/kg. In our experimental conditions, the PS extract at doses >or=12.5mg/kg proved to be more active than ranitidine at 50mg/kg.     

Antiulcerogenic activity of Zizyphus lotus (L.) extracts

Oral administration of aqueous extracts of Zizyphus lotus root barks (50-200 mg/kg) leaves (50-200 mg/kg) and fruits (200-400 mg/kg) produced a significant (p<0.01) and dose dependent inhibition to the acute ulcer induced by HCl/ethanol solution. The methanolic (MeOH), ethyl acetate (EtOAc) and chloroformic (CHCl(3)) leaves extracts when administered orally at the dose of 200 mg/kg, exhibited a significant (p<0.01) inhibition of gastric lesions by 45%, 76% and 33%, respectively. Indeed, methanolic and ethyl acetate root barks extracts significantly reduced the gastric lesions by 47% and 41%, respectively. While the chloroformic root barks extract had no significant activity (19%). The effect of all extracts was compared with cimetidine (100 mg/kg, 62%) and omeprazole (30 mg/kg, 93%). Volume, pH and acidity of gastric juice were studied in pylorus-ligated rats. Root barks (200 mg/kg, p<0.01), leaves (200 mg/kg, p<0.01) and fruits (400 mg/kg, p<0.05) aqueous extracts showed significant reduction of gastric juice secretion in pylorus ligated rats, whereas the other extracts did not show any significance. Thus, Zizyphus lotus extracts act essentially as cytoprotective agents, which support the antiulcer effect of this plant in the traditional medicine.     

Gastric antisecretory and antiulcer activities of an ethanolic extract of Bidens pilosa L. var. radiata Schult. Bip

Bidens pilosa var. radiata Schult. Bip. is used in folk medicine to treat stomach disorders including peptic ulcers. The ethanolic extract (0.5-2 g/kg) decreased the gastric juice volume, acid secretion, as well as pepsin secretion in pylorus ligated rats. B. pilosa extract showed antiulcer activity against indomethacin-induced gastric lesions. The extract effectively inhibited gastric haemorrhagic lesions induced by ethanol, and with an effective dose of 2 g/kg being more potent than sucralfate (400 mg/kg). In contrast, ranitidine (50 mg/kg) failed to reduce these lesions. These results indicate that B. pilosa ethanolic extract exerts a cytoprotective effect in addition to its gastric antisecretory activity that could be due, partly at least, to the presence of flavonoids of which quercetin was identified by HPLC.     

Antiulcerogenic effect and acute toxicity of a hydroethanolic extract from the cashew (Anacardium occidentale L.) leaves

The antiulcerogenic effect of a hydroethanolic extract of Anacardium occidentale L. leaves was investigated. The extract inhibited gastric lesions induced by HCl/ethanol in female rats. A dose-response effect study showed that the ED50 was 150 mg/kgb.w. Extract doses higher than 100 mg/kgb.w. were more effective than 30 mg/kg of lansoprazol in inhibiting gastric lesions. A methanolic fraction (257.12 mg/kg) which reduced gastric lesion at 88.20% is likely to contain the active principle of the antiulcer effect. No signs of acute toxicity were observed when mice were treated with extract dose up to 2000 mg/kgb.w. A chemical analysis of the extract allowed the identification of phenolic compounds as the major components. Glycosylated quercetin, amentoflavone derivate and a tetramer of proanthocyanidin were identified by liquid chromatography coupled to mass spectrometry. The level of total phenolics in the extract was evaluated at 35.5% and flavonoid content was 2.58%.     

Effects of Azadirachta indica extract on gastric ulceration and acid secretion in rats

The effect of Azadirachta indica extract on gastric ulceration was studied in albino rats. Azadirachta indica extract (100-800 mg/kg p.o., 100-25 mg/kg i.p.) significantly inhibited gastric ulceration induced by indomethacin (40 mg/kg). Administration of 800 mg/kg p.o. and 250 mg/kg i.p. caused 100% cytoprotection against indomethacin (40mg/kg, i.p.)-induced gastric ulceration. This action was accompanied by a dose-dependent decrease in total gastric acidity. In order to investigate the probable mechanism of Azadirachta indica antiulcer activity, the effect of the extract alone and in combination with histamine (1mg/kg) and cimetidine (0.12 mg/kg) on gastric acid secretion in situ was studied. Azadirachta indica (250 mg/kg) significantly inhibited the basal and histamine-induced gastric acid secretion. Cimetidine seemed to augment Azadirachta indica inhibition of gastric acid secretion.The results suggest that the stem bark extract of Azadirachta indica possesses antiulcer agents, which probably act via histamine H(2) receptor.     

Pharmacological assay of Cordia verbenacea. III: Oral and topical antiinflammatory activity and gastrotoxicity of a crude leaf extract

The antiinflammatory effects and gastrotoxicity of a lyophilized 70% ethanol extract of the leaves of Cordia verbenacea were investigated through experimental models in rats and mice. The oral administration of 1.24 mg/kg of the extract significantly inhibited nystatin-induced oedema. Topical application of the extract at a dose of 0.09 mg/ear in mice was clearly more effective than 1.0 mg/ear of naproxen in the reduction of the ear oedema induced by corton oil. At antiinflammatory doses, the extract showed an important protective effect on the gastric mucosa, reducing significantly the number of gastric lesions.     

Gastric cytoprotective anti-ulcer effects of the leaf methanol extract of Ocimum suave (Lamiaceae) in rats

The anti-ulcerogenic potential of the leaf methanol extract of Ocimum suave (Lamiaceae) was investigated using four methods of gastric lesion induction in experimental Wistar rats (150-200 g): (1) HCl/ethanol-induced gastric lesions, (2) Absolute ethanol-induced gastric lesions, (3) Indomethacin-HCl/ethanol-induced gastric lesions, (4) Pylorus ligation-induced gastric lesions. Administration of the extract of O. suave to the rats by oral route (75-500 mg/kg) dose-dependently prevented the formation of acute gastric lesions induced using the four experimental techniques. The dose-dependent reduction of lesion formation was in all cases accompanied by significant increases in gastric mucus production. At the dose of 250 mg/kg there was complete inhibition of gastric lesions induced using the HCl/ethanol solution. Pre-treatment, by intraperitoneal route, with indomethacin significantly reduced the ability of the extract to inhibit the formation of HCl/ethanol-induced lesions. When the rats were subjected to pylorus ligation, the dose of 500 mg/kg completely inhibited lesion formation but did not have any effect on gastric acid secretion compared with the controls. The mucus secretion promoting effect of the extract was most significant when the gastric environment was highly acidic. These results suggest that a new anti-ulcer therapy regimen may be formulated which does not require the use of antacids and anti-secretory agents.     

Antiulcerogenic activity of ethanol extract of Solanum variabile (false "jurubeba")

The ethanol extract (EE) of the aerial parts of Solanum variabile Mart. (Solanaceae) was investigated for its ability to prevent ulceration of the gastric and duodenal mucosa at different doses. Its ability to heal chronic ulcer processes was also evaluated. When the HCl/ethanol solution was used to induce gastric ulcer, the EE produced a significant dose-dependent reduction of lesion formation of 51, 74 and 89%, at doses of 250, 500 and 1000 mg/kg, respectively. The 100 mg/kg dose had no significant activity. The EE also significantly reduced the gastric lesions induced by the combination of indomethacin and bethanechol (60 and 72%) at doses of 500 and 1000 mg/kg and also reduced stress-induced gastric ulcer (41%) but only at the doses of 1000 mg/g (P < 0.05). The pylorus-ligature experiment demonstrated that the highest EE dose affected significantly the gastric juice parameters by increasing pH values from 4.08 (negative control) to 5.42 and decreasing acid output from 7.16 (negative control) to 4.26 mEq.mL, 4h. A decrease of gastric contents from 370 mg (negative control) to 240 mg was also observed. The results obtained in the chronic gastric ulcer model indicated that a single oral dose of Solanum variabile (1000 mg/kg) administered for 14 consecutive days accelerated the ulcer healing by 46% compared to a 55% effect of cimetidine. Also, at the dose of 1000 mg/kg, the EE inhibited the onset of duodenal lesions by 64%. The data suggest that the EE of Solanum variabile has a significant preventive, curative and duodenal anti-ulcer effect.     

Evaluation of the antiulcerogenic activity of Maytenus robusta (Celastraceae) in different experimental ulcer models

Maytenus robusta (Celastraceae) is used in folk medicine for the treatment of stomach ulcers and is very well adapted to the South of Brazil. Maytenus ilicifolia is the main species of the Celastraceae family, and is used in the treatment of gastric ulcers. However, Maytenus ilicifolia is presently at the stage of extinction, due to indiscriminate use in Brazil. Thus, the use of Maytenus robusta in phytotherapeutic preparations, instead of Maytenus ilicifolia, is suggested. However, there have been no reports regarding the antiulcer activity of Maytenus robusta extract. Therefore, this study was carried out to evaluate the antiulcerogenic property of the hydroalcoholic extract of aerial parts of Maytenus robusta. The antiulcer assays were performed using the following protocols: nonsteroidal anti-inflammatory drug (NSAID)-induced ulcer, ethanol-induced ulcer, and stress-induced ulcer. The effects of the extract on gastric content volume, pH and total acidity, using the pylorus ligated model, were also evaluated. In the ethanol-induced ulcer model, it was observed that the treatment with Maytenus robusta extract significantly reduced the lesion index in 75.1 +/- 8.6, 85.0 +/- 9.2, 86.6 +/- 7.4 and 75.5 +/- 5.3 for the groups treated with 50, 250 and 500 mg/kg of Maytenus robusta and positive control (omeprazole 30 mg/kg), respectively. Also were observed significant inhibition in lesion index in the indomethacin-induced ulcer model, being the decrease of the 62.5 +/- 7.1, 62.5 +/- 6.1, 63.6 +/- 5.5 and 96.2 +/- 3.6 for groups treated with 50, 250 and 500 mg/kg of Maytenus robusta and positive control (cimetidine 100 mg/kg), respectively. Results similar were observed in the stress-induced ulcer model, where the inhibition of ulcer lesions were 71.3 +/- 5.5, 72.7 +/- 6.3, 76.5 +/- 7.1 and 92.3 +/- 7.5 for the groups treated with 50, 250 and 500 mg/kg of Maytenus robusta and positive control (cimetidine 100 mg/kg), respectively. Regarding the model of gastric secretion, a reduction in the volume of gastric juice volume and total acidity was observed, as well as an increase in gastric pH. The results of the present study showed that Maytenus robusta hydroalcoholic extract displays gastroprotective activity. These results were similar to those obtained in studies carried out with Maytenus ilicifolia, which indicate that this species could be used in phytotherapeutic preparations as a substitute for Maytenus ilicifolia. This work also corroborates the traditional indication of Maytenus robusta, contributing to its pharmacological validation.     

Gastroprotective activity of Pradosia huberi on experimentally induced gastric lesions in rodents: role of endogenous sulphydryls and nitric oxide

Pradosia huberi is a medicinal plant very common in the Amazonian forest population. The research interest in this plant is justifiable because of its potential medicinal value in gastritis and gastric ulcer mentioned in local folk medicine. In this paper, we evaluated the acute toxicity and antiulcerogenic effect of a hydroalcoholic extract (HAE) obtained from Pradosia huberi barks in rodents. No acute toxicological sign or symptom was observed in animals treated with the highest dose (5000 mg/kg, p.o.) of Pradosia huberi. In the HCl/EtOH-induced gastric ulcer model, HAE demonstrated significant inhibition of the ulcerative lesion index by 73% (500 mg/kg) and 88% (1000 mg/kg), respectively, in relation to the control value (p<0.05). The gastric damage induced by absolute ethanol in rats was effectively reduced by 84, 88 and 81% (250, 500 and 1000 mg/kg) when compared with the control group (p<0.01). In the NSAID-induced lesion model, HAE also showed antiulcerogenic effect with decrease in gastric lesions of 56% (250 mg/kg), 57% (500 mg/kg) and 67 % (1000 mg/kg) when compared with animals treated with vehicle (p<0.05). In the gastric ulcer induced by pylorus ligature model, the administration of HAE by oral and intraduodenal routes inhibited the gastric lesion index by 79 and 52% (500 mg/kg), respectively. HAE administered orally or intraduodenally was able to change gastric juice parameters (pH, volume and acid output) as well as those treated with cimetidine. The treatment with HAE (p.o.) significantly increased gastric volume, the pH values and promoted reduced acid output (p<0.01). By comparative effect (intraduodenal and oral route), we observed that HAE was better for local activity in gastric mucosa than in systemic action. HAE also has a non-specific activity when found to be the inhibitor of intestinal motility (p>0.01). The mechanism of action of HAE did not seem to be related to the NO-inhibitor but showed the participation of endogenous sulphydryl group in the gastroprotective action.     

Antiulcerogenic effect of Croton urucurana Baillon bark

Ethnopharmacological relevance

Croton urucurana (Euphorbiaceae) bark is used to treat gastric ulcers. However, to our knowledge, no study has been conducted to confirm this therapeutic property.

Aim of the study

To evaluate the antiulcerogenic effect and any possible toxic effects of Croton urucurana bark in an induced gastric ulcer model in rats.

Materials and methods

The preventive and healing properties of Croton urucurana bark methanol extract (CUE) were evaluated in experimental models of acute (ethanol and indomethacin) and chronic (acetic acid) gastric ulcers. The gastric juice and mucous were evaluated using the pylorus ligation model, while the gastroprotective action of sulphydryl compounds and nitric oxide were analysed using the ethanol model. The toxicity was evaluated with acute and subacute toxicity tests.

Results

No signs of toxicity were observed in the parameters analysed. All of the CUE doses tested (50, 100 and 250 mg/kg) significantly reduced the gastric lesions by 70.25, 95.40 and 98.71%, respectively. Treatment with 30 mg/kg lansoprazole (positive control) inhibited 82.58% of the gastric lesions. In the indomethacin model, the 50, 100 and 250 mg/kg doses of CUE significantly reduced gastric damage by 67.85, 82.50 and 71.01%, respectively, and the positive control, cimetidine (200 mg/kg), reduced gastric damage by 91.02%. The CUE (100 mg/kg) and cimetidine (200 mg/kg) treatments significantly reduced the ulcerative pathology induced by acetic acid, promoting 81.55 and 72.62% healing, respectively. Nitric oxide did not change the cytoprotection generated by CUE. However, the antiulcerogenic activity of CUE appears to involve sulphydryl compounds because CUE activity was inhibited in animals receiving a sulphydryl compound blocker. In addition, CUE exhibited systemic effects, increasing mucous production and decreasing gastric acidity.

Conclusions

The present study shows that Croton urucurana bark exerts gastroprotective activity in rats without causing toxicity. This effect appears to involve sulphydryl compounds, increasing mucus production and reducing gastric acidity.     

Inhibition of experimental gastric lesion and inflammation by Phyllanthus amarus extract

Methanolic extract of Phyllanthus amarus Shum & Thonn (Euphorbiaceae) 50, 200, and 1000 mg/kg body weight significantly inhibited gastric lesions, induced by intragastric administration of absolute ethanol (8 ml/kg). Mortality, increased stomach weight, ulcer index, and intraluminal bleeding were reduced significantly by Phyllanthus amarus. Biochemical analysis indicated that reduced glutathione (GSH) of gastric mucosa produced by ethanol administration was significantly elevated by treatment with Phyllanthus amarus extract. Aqueous and methanol extracts of Phyllanthus amarus produced an inhibition of rat paw edema up to 42% compared to control in 3h and continued up to 8h. Anti-oxidant activity of the extract as well as presence of tannins in the extract may be responsible for these observed activities.     

The antiinflammatory, gastroprotective and antioxidant activities of Hieracium gymnocephalum extract

The present study investigated the antiinflammatory, gastroprotective and antioxidant activities of a CH(2)Cl(2) extract of western Balkan endemic Hieracium gymnocephalum Griseb. ex Pant. (Compositae). The carrageenan-induced rat paw oedema test was used as an experimental model for screening the antiinflammatory activity. The extract was administrated p.o. in doses of 25, 50, 100 and 200 mg/kg to rats and its effects compared with indomethacin, used p.o. as a reference drug. The results showed that the investigated extract reduced the oedema in a concentration-dependent manner. The obtained antiinflammatory effect was 5.9%, 11.7%, 31.2% and 44.1% at doses of 25, 50, 100 and 200 mg/kg, respectively, being statistically significant at a dose of 100 mg/kg. Indomethacin had a strong antiinflammatory effect of 73.4% at a dose of 8 mg/kg, but caused large gastric lesions. When the plant extract in the highest tested dose (200 mg/kg) was concomitantly given with indomethacin, the antiinflammatory effect was slightly enhanced, but the gastric lesions were significantly reduced. The antioxidant activity of the H. gymnocephalum extract, investigated using DPPH radical assay, OH-radical assay and TBA-test, was not substantial.     

Anti-ulcer actions of the bark methanol extract of Voacanga africana in different experimental ulcer models in rats

The antiulcerogenic effects of the bark methanol extract of Voacanga africana were studied using various experimental ulcer models in rats. The effects of the extract on the volume of gastric juice, gastric pH, acid output, mucus production and peptic activity were recorded, as well as the preventive action against lesions caused by HCl/ethanol and indomethacin. Oral administration of the extract (500-750 mg/kg) inhibited the formation of gastric lesions induced by HCl/ethanol (40-63% inhibition). The inhibitory effect against HCl/ethanol was significantly (P<0.01) suppressed by pre-treatment of the rats with indomethacin (30 mg/kg, i.p.). The extract significantly reduced gastric lesion formation in pylorus ligated rats, but this was not associated with an increase in gastric mucus production or with a reduction in acid content, volume of gastric secretion or pepsin activity of the gastric juice.     

Anti-ulcer, anti-inflammatory and antioxidant activities of the n-butanol fraction from Pteleopsis suberosa stem bark

Pteleopsis suberosa Engl. et Diels (Combretaceae) is a tree distributed in many African countries. The decoction from the stem bark is orally administered for the treatment of gastric ulcers in traditional medicine. Previous pharmacological studies reported the anti-ulcer activity of extracts from P. suberosa stem bark. In the present study, the anti-ulcer and anti-inflammatory effects of the n-butanol fraction (RBuOH) obtained from a methanol extract of P. suberosa bark were investigated on ethanol-induced gastric ulcers in rats and carrageenan-induced paw oedema in mice. Misoprostol (0.50 mg/kg, p.o.) and indomethacin (8.00 mg/kg, p.o.) were used as positive controls for anti-ulcer and anti-inflammatory activities, respectively. Results showed that RBuOH treatment significantly reduced the incidence of gastric lesions (50 mg/kg, P<0.05; 100 and 200 mg/kg, P<0.01) and restored the decreased levels of total sulfhydryl groups (T-SH) and non-protein sulfhydryl groups (NP-SH) (50, 100 mg/kg, P<0.05; 200 mg/kg, P<0.01) in the stomach homogenate. Moreover, RBuOH treatment attenuated MDA levels as index of lipid peroxidation in gastric mucosa. Administration of RBuOH at the same dosage (50, 100 and 200 mg/kg) reduced significantly (P<0.01) carrageenan-induced paw oedema in dose-dependent manner (from 42.81% to 87.81% inhibition, 5h after carrageenan injection). The anti-inflammatory effect of RBuOH at 200 mg/kg was comparable with that of indomethacin. Finally, RBuOH proved to possess elevated free radical scavenger capacity on 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay (IC(50) 23.48 microg/ml) which may contribute to the observed anti-ulcer and anti-inflammatory activities.     

Antiulcer action of Microgramma squamulosa (Kaulf.) Sota.

Microgramma squamulosa (Kaulf.) Sota (Polypodiaceae) is commonly used as an antiulcer agent in the state of São Paulo, mainly in the upper land. The present work aims to study the antiulcer action of the crude extract of the plant rhizome and its toxicity. The effective dose was determined through acute ulcer induction test by stress. Using a determined dose, we performed a test against ulcer through acute induction by ethanol and hydrochloric acid, using cimetidine and misoprostol as reference drugs in both tests. The same extract, its ethanol and ethanol+water (1:1) fractions and the reference drug cimetidine were tested through subchronic induction test with acetic acid. The subchronic toxicity test was performed using a dose of 800 mg/kg of the crude extract, orally administered for 30 days. Finally the extracts and fractions were analysed in order to determine the main chemical groups of substances.     

The anti-ulcer effect in rats of ginger constituents

The effects of ginger, a pungent stomachic natural medicine, on HCl/ethanol-induced gastric lesions in rats, were examined. The orally administered acetone extract at 1000 mg/kg and zingiberene, the main terpenoid from acetone extract, at 100 mg/kg significantly inhibited gastric lesions by 97.5 and 53.6%, respectively. 6-Gingerol, the pungent principle, at 100 mg/kg significantly inhibited gastric lesions by 54.5%. These results suggest that zingiberene, the terpenoid and 6-gingerol are important constituents in stomachic medications containing ginger.     

Reversal of cisplatin-induced delay in gastric emptying in rats by ginger (Zingiber officinale)

Cisplatin causes nausea, vomiting and inhibition of gastric emptying. We have demonstrated the antiemetic effect of the acetone and ethanolic extract of ginger (Zingiber officinale, Roscoe, Zingiberacae) against cisplatin-induced emesis in dogs. In the present study, the acetone and 50% ethanolic extract of ginger in the doses of 100, 200 and 500 mg/kg (p.o.) and ginger juice, in the doses of 2 and 4 ml/kg, were investigated against cisplatin effect on gastric emptying in rats. All three ginger preparations significantly reversed cisplatin-induced delay in gastric emptying. The ginger juice and acetone extract were more effective than the 50% ethanolic extract. The reversal produced by the ginger acetone extract was similar to that caused by the 5-HT₃ receptor antagonist ondansetron; however, ginger juice produced better reversal than ondansetron. Therefore, ginger, an antiemetic for cancer chemotherapy, may also be useful in improving the gastrointestinal side effects of cancer chemotherapy.     

吴茱萸水提物对乙醇造成的大鼠胃损伤的保护作用

目的：研究吴茱萸水提物对乙醇造成的大鼠急性胃损伤的保护作用及其可能的机制。方法：大鼠经腹腔注射424.8,141.6,47.6 mg·kg^-1 3种不同剂量的吴茱萸水提物后,用ex-vivo chamber法测定50%乙醇造成胃损伤前后的胃电压（PD）变化；另外,经在体胃内插管收集灌流液后,采用硝酸还原酶法测定灌流液中一氧化氮的代谢产物（NO_x）的含量,并通过形态测量法测定胃损伤程度。结果：与对照组比较,不同剂量的吴茱萸水提物对促进PD的恢复和降低损伤指数均有显著作用（P<0.05）,并呈现出剂量依赖性。吴茱萸水提物能剂量依赖性地升高胃损伤前后灌流液中NO_x的水平；尤其当剂量为424.8 mg·kg^-1时,与对照组比较,灌流液NO_x的含量显著增加（P<0.01）。结论：吴茱萸水提物对50%乙醇造成的大鼠急性损伤具有较好的保护作用；其机制与增强胃黏膜屏障功能,促进胃黏膜内源性NO合成有关。