Constituents and antiulcer effect of Alchornea glandulosa: Activation of cell proliferation in gastric mucosa during the healing process

Alchornea glandulosa (Euphorbiaceae) is a plant used in folk medicine as an antiulcer agent. Rats pretreated with methanolic extract obtained from the leaves of A. glandulosa (AG) showed a dose-dependent effect and significant reduction of gastric ulcers induced by absolute ethanol at the doses of 500 (57%) and 1000 mg/kg (35%) in relation to the control group. Pretreatment of mice with AG (500, 1000 mg/kg, p.o.) showed dose-dependent activity and significantly decreased the severity of lesions caused by HCl/ethanol and by non steroidal anti inflammatory drug-induced gastric lesions. Pretreatment with AG also induced antisecretory action via local and systemic routes and a significant decrease in the total gastric acid content. The gastroprotective effects of AG involved the participation of nitric oxide and increased levels of endogenous sulfhydryl compounds, which are defensive mechanisms of the gastrointestinal mucosa against aggressive factors. The ability of AG to heal gastric ulcers was evaluated after 14 consecutive days of treatment. The results showed that single oral administrations of AG (250 mg/kg/once daily) potently stimulates gastric epithelial cell proliferation that contributes to the accelerated healing of gastric ulcers induced by acetic acid. In addition, no subacute toxicity (body weight gain, vital organs, and serum biochemical parameters) was observed during treatment with AG. Phytochemical investigation of AG led to the isolation of myricetin-3-O-alpha-L-rhamnopyranoside, quercetin-3-O-alpha-L-arabinopyranoside, quercetin-3-O-beta-D-galactopyranoside, quercetin, amentoflavone, methyl gallate, gallic acid, and pterogynidine. We also established the phytochemical profile of AG with the quantification of total phenolic compounds. These compounds may contribute to the observed antiulcerogenic effects of AG.

The antiulcer effect of Croton cajucara Benth in normoproteic and malnourished rats

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Preliminary studies of Mammea americana L. (Guttiferae) bark/latex extract point to an effective antiulcer effect on gastric ulcer models in mice

Plant extracts are some of the most attractive sources of new drugs and have shown promising results for the treatment of gastric ulcers. Several folk medicinal plants and herbs have been used to treat gastrointestinal disorders, including gastric ulcers. Mammea americana L. (Guttiferae) fruit is very common in the diet of the population of northern South America. Our research interest in this plant arose because of its potential medicinal value as a tonic and against stomachache, as used in folk medicine. In this paper we evaluated three different extracts (ethanolic/EtOH, methanolic/MeOH and dichloromethane/DCM) obtained from M. americana L., for their ability to protect the gastric mucosa against injuries caused by necrotizing agents (0.3 M HCI/60% EtOH), hypothermic restraint stress, nonsteroidal anti-inflammatory drugs (NSAID, indomethacin) and pylorus ligation. In the HCI/EtOH-induced gastriculcer model, EtOH and DCM extracts demonstrated significant inhibition of the ulcerative lesion index by 54% (12.0 +/- 2.6 mm) and 86% (3.7 +/- 1.8 mm), respectively, in relation to the control value (26.0 +/- 1.4 mm) (p < 0.000 1). In the NSAID/cholinomimetic-induced lesion model, both EtOH and DCM extracts showed antiulcerogenic effects with significant reduction in the damage to these gastric lesions of 36% (8.3 +/- 2.0 mm) and 42% (7.5 +/- 1.4 mm), respectively, as compared to the control group (13.0 +/- 0.9 mm) (p < 0.0001). In the gastric ulcer induced by hypothermic-restraint stress, both extracts also showed significant activity, and inhibited the gastric lesion index by 58% and 75%, respectively. The EtOH and DCM extracts also changed gastric juice parameters as well as those of cimetidine, decreased gastric acid secretion significantly (p < 0.0001), increased pH values and promoted reduced acid output (p < 0.0001). In all gastric-ulcer-induced models, MeOH extract did not show any significant antiulcerogenic activity, nor did it change gastric-juice parameters (p > 0.05). The results suggest that EtOH and DCM extracts obtained from M. americana possess excellent antisecretory and/or gastrotective effect in all gastric ulcer models. These results suggest that the antiulcerogenic compound(s) present in M. americana may be clustered in the apolar fraction, which will be investigated by our group for the probable mechanisms of action. (c) 2004 Elsevier GmbH. All rights reserved.

Qualea grandiflora, a Brazilian Cerrado medicinal plant presents an important antiulcer activity

Qualea grandiflora is one of the species widely used in folk medicine to treat gastric ulcers in Cerrado of the central region of Brazil. The hydroalcoholic extract of bark (HE) of Qualea grandiflora was investigated for their ability to prevent and heal lesions in the gastric mucosa. The oral administration of HE exhibited antiulcer activity decreasing the ulcerative index induced by HCl/ethanol solution, indomethacin/bethanechol and stress. In the Shay model, results showed that HE (p.o.) only reduced the severity of gastric lesions without effects on pH, gastric acidity or volume. When given by intraduodenal route, HE changed the pH, but did not modify the other parameters of the gastric juice. These data were in accordance with those obtained when HE was administered orally for 14 days after gastric ulcers were induced by acetic acid in rats. HE presented healing process in subacute gastric ulcer induced by acetic acid in rats. Moreover, histological examinations showed the simple columnar epithelium, lamina propria with simple branched tubular glandules with dilated lumen and large amounts of mucus secretion. Phytochemical investigation of HE led to the detection of terpenes, steroids, saponins, phenolic compounds and tannins in this extract, which may be involved in the observed activity. (c) 2005 Elsevier B.V.. All rights reserved.

New steroidal saponins and antiulcer activity from Solanum paniculatum L.

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Antiulcerogenic activity of Terminalia chebula fruit in experimentally induced ulcer in rats

Objective: The present study is to evaluate the antiulcer effect of hydroalcoholic (70%) extract of Terminalia chebula fruit. Materials and methods: Aspirin, ethanol and cold restraint stress-induced ulcer methods in rats were used for the study. The effects of the extract on gastric secretions, pH, total and free acidity using pylorus ligated methods were also evaluated. Results: Animals pretreated with doses of 200 and 500 mg/kg hydroalcoholic extract showed significant reduction in lesion index, total affected area and percentage of lesion in comparison with control group (P < 0.05 and P < 0.01) in the aspirin, ethanol and cold restraint stress-induced ulcer models. Similarly extracts increased mucus production in aspirin and ethanol-induced ulcer models. At doses of 200 and 500 mg/kg of T. chebula extract showed antisecretory activity in pylorus ligated model, which lead to a reduction in the gastric juice volume, free acidity, total acidity, and significantly increased gastric pH. Discussion and conclusion: These findings indicate that hydroalcoholic extract of the fruit T. chebula displays potential antiulcerogenic activity. This activity thus lends pharmacological credence to the suggested use of the plant as a natural remedy in the treatment or management of ulcer.

Studies on the Antiulcerogenic and Antihepatotoxic Potential of Chitosan and Glucosamine in Experimental Rats

The present study examined the antiulcer effect of glucosamine on mucosal antioxidant defense system in ibuprofen-induced peptic ulcer in male albino rats. The results of the present study indicate that the pre-oral administration of chitosan and glucosamine maintain near to the normal status the activities of the mucosal antioxidant enzymes and the level of GSH (Glutathione), which protect mucosa against oxidative damage by decreasing the lipid peroxidation and strengthening the mucosal barrier, and which are the first line of defense against exogenous ulcerogenic agents. In this study indicate that the oral pre-treatment of chitosan and glucosamine can prevent ibuprofen-induced peptic ulcer in rats.This study can be concluded that co-administration of chitsosan and glucosamine can effectively prevent the isonized and rifampicin induced hepatotoxicity in rats.Comparatively, chitosan was found to have better results than glucosamine in alleviating the hepatic disorders.

Studies om the Antiulcerogenic and Antihepatotoxic Potential of Chitosan and Glucosamine in Eeperimental Rats

The present study examined the antiulcer effect of glucosamine on mucosal antioxidant defense system in ibuprofen-induced peptic ulcer in male albino rats. The results of the present study indicate that the pre-oral administration of chitosan and glucosamine maintain near to the normal status the activities of the mucosal antioxidant enzymes and the level of GSH (Glutathione), which protect mucosa against oxidative damage by decreasing the lipid peroxidation and strengthening the mucosal barrier, and which are the first line of defense against exogenous ulcerogenic agents. In this study indicate that the oral pre-treatment of chitosan and glucosamine can prevent ibuprofen-induced peptic ulcer in rats.This study can be concluded that co-administration of chitsosan and glucosamine can effectively prevent the isonized and rifampicin induced hepatotoxicity in rats.Comparatively, chitosan was found to have better results than glucosamine in alleviating the hepatic disorders

Antiulcerogenic activity and toxicity of bauhinia holophylla hydroalcoholic extract

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Evaluation of antiulcer activity of the main phenolic acids found in Brazilian Green Propolis

Aim of the study: In a previous study, our group described the gastric protective effect of the hydroalcoholic extract of Brazilian green propolis. The main compounds found in Brazilian green propolis include phenolic acids, such as: caffeic, ferulic, p-coumaric and cinnamic acids. This study was therefore carried out to evaluate the antiulcerogenic property of the main phenolic acids found in Brazilian Green Propolis.Material and methods: The anti-ulcer assays were performed using the following protocols: nonsteroidal-antinflammatory drug (NSAID)-induced ulcer, ethanol-induced ulcer, and stress-induced ulcer. The effects of the phenolic acids on gastric content volume, pH and total acidity, using the pylorus ligated model, were also evaluated.Results: It was observed that treatment using doses of 50 and 250 mg/kg of caffeic, ferulic, p-coumaric and cinnamic acids and positive controls (omeprazol or cimetidine) significantly diminished the lesion index, the total area of the lesion and the percentage of lesion in comparison with the negative control groups. In addition, the percentage of ulcer inhibition was significantly higher in the groups treated with the different phenolic acids, cimetidine or omeprazol, in all the protocols used, compared with the negative control groups. In the model to determine gastric secretion, using ligated pylorus, treatment with phenolic acids and cimetidine reduced the volume of gastricjuice and total acidity and significantly increased the gastric pH (p < 0.05), compared with the control group, with the exception of the group treated with 50 mg/kg of p-coumaric acid, in which no significant difference was observed, compared with the control. In relation to the acute toxicity, none sign of toxicity was observed when phenolic acids, used in this study, were administered for rats in dose of 2000 mg/kg.Conclusions: In conclusion, the results of this study show that caffeic, ferulic, p-coumaric and cinnamic acids display antiulcer activity. (c) 2008 Elsevier B.V. All rights reserved.

Can a Strychnos species be used as antiulcer agent? Ulcer healing action from alkaloid fraction of Strychnos pseudoquina St. Hil. (Loganiaceae)

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Can the aqueous decoction of mango flowers be used as an antiulcer agent?

This study was designed to determine the effect of Mangifera indica flowers decoction, on the acute and subacute models of induced ulcer in mice and rats. A single oral administration of the aqueous decoction (AD) from M. indica up to a dose of 5 g/kg, p.o. did not produce any signs or symptom of toxicity in the treated animals. The oral pre-treatment with AD (250, 500 and 1000 mg/kg) in rats with gastric lesions induced by ethanol, decreased the gastric lesions from 89.0 +/- 6.71 (control group) to 9.25 +/- 2.75, 4.50 +/- 3.30 and 0, respectively. Pretreatment with AD (250, 500 and 1000 mg/kg) to mice with HCl/ethanol- or stress-induced gastric lesions resulted in a dose-dependent significant decrease of lesion index. In the piroxicam-induced gastric lesions, the gastroprotective effect of AD was reducing with the increase of the AD dose. In the pylorus-ligature, AD (p.o.) significantly decreased the acid output indicating the antisecretory property involved in the gastroprotective effect of M. indica. Treatment with AD during 14 consecutive days significantly accelerated the healing process in subacute gastric ulcer induced by acetic acid in rats. Pretreatment with N-nitro-L-arginine methyl ester (L-NAME), an inhibitor of NO-synthase, did not abolish the gastroprotective effects (99% with saline versus 80% With L-NAME) of AD against ethanol-induced gastric lesions. Pretreatment with N-ethylmaleimide (NEM), a blocker of endogenous sulphydryl group, significantly abolished the protective effects of AD against ethanol-induced gastric ulcers (95% with saline versus 47% with NEM). Phytochemical screening showed the presence of steroids, triterpenes, phenolic compounds and flavonoids. Estimation of the global polyphenol content in the AD was performed by Folin-Ciocalteu method and showed approximately 53% of total phenolic on this extract. These findings indicate the potential gastroprotective and ulcer-healing properties of aqueous decoction of M. indica flowers and further support its popular use in gastrointestinal disorders in Caribbean. (c) 2005 Elsevier B.V.. All rights reserved.

The gastroprotective effect of the essential oil of Croton cajucara is different in normal rats than in malnourished rats

It has been shown previously that malnourished rats are resistant to acute gastric lesions but not to subchronic gastric ulceration. It also has been demonstrated that the essential oil obtained from the bark of Croton cajucara (Sacaca) has antiulcer properties. In the present study, the ability of this essential oil to prevent the formation of gastric ulcers in rats fed a diet with 17 % protein (normoproteic rats) or 6 % protein (malnourished rats) was investigated. At a dose of 100 mg/kg body weight, orally, the essential oil significantly reduced the gastric injury caused by indomethacin (25 % after 2 h and 70 % after 4 h) only in normoproteic rats. In the pylorus ligature model, the essential oil increased the pH and gastric volume, but decreased the total acid concentration in both groups when compared to the respective control group. The essential oil significantly increased prostaglandin E2 production in glandular cells by 50 % compared to the controls in both groups of rats. In addition, the amount of gastric mucus was two-fold higher in malnourished rats than in normoproteic rats. The present results show that the enhanced protective effect of essential oil in malnourished rats involved an increase in prostaglandin E2 production and mucus secretion, which are both factors that protect the gastric mucosa against damage. In agreement with this, malnourished rats always had a lower number of acute gastric ulcers.

Gastric antiulcer activity of Syngonanthus arthrotrichus SILVEIRA

Syngonanthus arthrotrichus SILVEIRA, popularly known as sempre-vivas mini-saia, is found in mountains of the Espinhaco range in the Brazilian states of Bahia and Minas Gerais. Extracts of this species contain several constituents, including flavonoids which may have antiulcerogenic activity. An ethanolic extract (EEOH), and flavonoid-rich (FRF) and flavonoid-deficient (FDF) fractions obtained from the scapes of S. arthrotrichus were investigated for their ability to prevent ulceration of the gastric mucosa in mice and rats. In the ethanol/HCl-induced ulcer model, lansoprazole (30 mg/kg), EEOH (50, 100, 250 mg/kg) given orally protected the gastric mucosal against injury in mice by 79%, 78%, 73%, and 64% respectively. In the ethanol-induced gastric ulcer model in rats, the lansoprazole (30 mg/kg), FRF and FDF (100 mg/kg) significantly protected the gastric mucosal of rats by 65%, 38% and 25% respectively when compared with the negative control group. In indomethacin/ bethanechol-induced gastric ulcers, cimetidine (100 mg/kg) and the EEOH (100, 250 mg/kg) inhibited gastric ulcer formation by 73%, 55% and 32% respectively. In this exactly model other treatments as cimetidine, FRF and FDF (100 mg/kg) each caused 54%, 36% and 45% inhibition, respectively. In the stress-induced gastric ulcer model, cimetidine (100 mg/kg) and the EEOH (50, 100, 250 mg/kg), inhibited gastric ulcer formation by 63%, 73%, 68% and 69% respectively. In the same model, cimetidine, FRF and FDF (100 mg/kg) significantly protected the gastric mucosal of the mice by 60%, 51% and 47% when compared to the control group. In pylorus-ligated mice, cimetidine (positive control) and FRF significantly decreased gastric acid secretion, increased gastric pH and reduced the acid output when compared to the negative control. FDF had no significant effect on these parameters. The protection provided by FRF probably involved an antisecretory mechanism mediated by flavonoids which were absent in FDF. The amount of adherent mucous in the stomach contents was also evaluated with the treatments carbenoxolone (200 mg/kg), FRF and FDF (100 mg/kg) treatment. Each treatments significantly increased the amount of adherent mucous in the gastric juice (8.67 +/- 1.73, 3.35 +/- 1.59, 2.1 +/- 0.41 mg/g of wet tissue, respectively) compared to the control group, indicating a cytoprotective action on the gastric mucosa. Treatment with FRF plus indomethacin and FDF plus indomethacin reduced the prostaglandin biosyntesis (13.6 +/- 6.5, 27 +/- 5.5 pg/well) by the mucosa, indicating that the cytoprotective action on the gastric mucosa was not related to the level of prostaglandins. Only FDF (38 +/- 17 pg/well) maintained the level of prostaglandins and guaranteed the integrity of the mucosa. The results indicate that the EEOH, FRF and FDF have antisecretory and cytoprotective actions, that may be related to the presence of luteoline in the extract and active fractions.

Nerolidol, an antiulcer constituent from the essential oil of Baccharis dracunculifolia DC (Asteraceae)

In this study, the antiulcerogenic effect of essential oil from Baccharis dracunculifolia was evaluated using the model of acute gastric lesions induced by ethanol. The ulcerative lesion index (ULI) was significantly reduced by oral administration of the essential oil of B. dracunculifolia at doses of 50, 250 and 500 mg/kg which reduced the lesions by 42.79, 45.70 and 61.61%, respectively. The analysis of the chemical composition of the essential oil from B. dracunculifolia by GC showed that this was composed mainly of mono- and sesquiterpenes and the majority compound was nerolidol. Therefore, antiulcerogenic activity of nerolidol (50, 250 and 500 mg/kg) was investigated using ethanol-, indomethacin- and stress-induced ulcer models in rat. In the stress-induced ulcer model, a significant reduction of the ULI in animals treated with nerolidol (50, 250 and 500 mg/kg) and cimetidine (100 mg/kg) was observed, compared to the control group (p < 0.05). The percentage of inhibition of ulcer was 41.22, 51.31, 56.57 and 53.50% in groups treated with 50, 250, 500 mg/kg of nerolidol and 100 mg/kg of cimetidine (positive control), respectively. Regarding ethanol- and indomethacin-induced ulcer models, it was observed that the treatment with nerolidol (250 and 500 mg/kg) significantly reduced the ULI in comparison with the control group (p < 0.05). The dose of 50 mg/kg reduced the parameters analyzed but this was not statistically significant. In the ethanol-induced model percentage of inhibition of ulcer was 34.20, 52.63, 87.63 and 50.87% in groups treated with 50, 250, 500 mg/kg of nerolidol and 30 mg/kg of omeprazol (positive control), respectively. In indomethacin-ulcer the percentage of inhibition of ulcer was 34.69, 40.80, 51.02 and 46.93% in groups treated with 50, 250, 500 mg/kg of nerolidol and 100 mg/kg of cimetidine (positive control), respectively. The results of this study show that nerolidol displays antiulcer activity, as it significantly inhibited the formation of ulcers induced in different animal models. However, further pharmacological and toxicological investigations, to delineate the mechanism(s) of action and the toxic effects, are required to allow the use of nerolidol for the treatment of gastric ulcer. © 2007 Verlag der Zeitschrift für Naturforschung.