Antiulcerogenic activity of Lantana camara leaves on gastric and duodenal ulcers in experimental rats

Ethnopharmacological relevance

Lantana camara L. (Verbenaceae), a widely growing shrub has been used in the traditional medicine for treating many ailments. The objective of the present study was to evaluate the effects of methanolic extract of Lantana camara leaves on gastric and duodenal ulcers.

Materials and methods

The antiulcerogenic effect of methanolic extract of Lantana camara was evaluated in aspirin induced gastric ulcerogenesis in pyloric ligated rats, ethanol induced gastric ulcer, and cysteamine induced duodenal ulcer models. The extract was administered orally at two different doses of 250 mg/kg and 500 mg/kg. The lipid peroxidation, reduced glutathione levels of ethanol induced gastric ulcer model and inhibition zone in diameter against Helicobacter pylori also determined.

Results

The L. camara extract significantly (P < 0.01) reduced ulcer index, total acidity and significantly (P < 0.01) increased the gastric pH of aspirin + pylorus-ligation induced ulcerogenesis and ethanol induced gastric ulcer models. The extract also significantly (P < 0.01) reduced the ulcer index of cysteamine induced duodenal ulcer. The L. camara showed significant (P < 0.01) reduction in lipid peroxidation and increase in reduced glutathione levels. The inhibition zone in diameter of extract against H. pylori was 20 mm.

Conclusion

The methanolic extract of Lantana camara leaves shown healing of gastric ulcers and also prevents development of duodenal ulcers in rats.     

Byrsonima intermedia A. Juss.: gastric and duodenal anti-ulcer, antimicrobial and antidiarrheal effects in experimental rodent models

Ethnopharmacological relevance

An ethnopharmacological survey indicated that the leaves of Byrsonima intermedia A. Juss. (Malpighiaceae), a medicinal species commonly found in the Brazilian Cerrado, can be used against gastroduodenal disorders, such as gastric ulcers and diarrhea.

Aim of the study

The objective of this study was to evaluate the effects of a methanolic extract of Byrsonima intermedia (MBI) leaves on gastric and duodenal ulcers and to assess the antimicrobial and antidiarrheal effects of this extract.

Material and methods

The anti-ulcerogenic effect of MBI was investigated with different ulcerogenic agents in rodents (mice and rats), including non-steroidal anti-inflammatory drug (NSAID), HCl/ethanol, pyloric ligature, absolute ethanol, cysteamine and ischemia–reperfusion. The gastroprotective effect of MBI was assessed by analysing the volume of gastric juice, pH, total acidity, mucus, NO, sulfhydryl compound, vanilloid receptor, glutathione (GSH) levels, and myeloperoxidase (MPO) activity in the gastric and duodenal mucosa. The gastric and duodenal healing effects of MBI were also evaluated during 7 or 14 days of treatment. The antidiarrheal action (measured by intestinal motility and diarrhea induced by castor oil) and anti-bacterial action of MBI against Staphylococcus aureus, Escherichia coli and Helicobacter pylori were also evaluated by microdilution methods.

Results

The phytochemical profile from MBI indicated the presence of phenolic acids, flavan-3-ols, oligomeric proanthocyanidins, and flavonoids. MBI (500 mg/kg, p.o.) significantly inhibited totally gastric and duodenal lesions (69%) and healed gastric (49% on 14 days) and duodenal lesions (45% on 7 and 14 days). The MBI exert gastroprotective action by participation of endogenous sulfhydryl compounds, vanilloid receptors and increase in GSH level to effective gastric and duodenal protection. MBI also displayed curative (42%) and preventive (49%) antidiarrheal effects by involvement of opiate receptors and also antimicrobial effects in vitro.

Conclusions

Byrsonima intermedia leaves present gastroprotective, healing and antidiarrheal activities, supporting previous claims that its traditional use can treat gastrointestinal disorders.     

Hymenaea stigonocarpa Mart. ex Hayne: A Brazilian medicinal plant with gastric and duodenal anti-ulcer and antidiarrheal effects in experimental rodent models

Ethnopharmacological relevance

Hymenaea stigonocarpa Mart. ex Hayne (Fabaceae) is a medicinal species commonly found in the Brazilian savannah. The stem bark of this medicinal plant, popularly known as “jatobá-do-cerrado”, is widely used in tea form to treat gastric pain, ulcers, diarrhoea and inflammation, whereas its fruits pulp is edible.

Aim of the study

The aim of this study was to investigate the antidiarrheal and anti-ulcer effects of a methanolic extract derived from the stem bark (MHs) and diet with fruit pulp of H. stigonocarpa.

Materials and methods

The antidiarrheal action of MHs was measured against the intestinal motility and diarrhoea induced by castor oil in mice. The preventive action of MHs (50, 100, 150 and 200 mg/Kg, by oral route (p.o.)) against peptic ulcers was evaluated in experimental rodent models challenged with absolute ethanol, non-steroidal anti-inflammatory drugs (NSAIDs), ischemia–reperfusion (I/R) (200 mg/Kg, p.o.) and cysteamine (200 mg/Kg, p.o.). The main anti-ulcer mechanisms of action of MHs were analysed as follows: evaluation of the gastric juice parameters, assessment of mucus adherence to the gastric wall, determination of the role of nitric oxide (NO) and sulfhydryl compounds (SH), glutathione (GSH) levels and myeloperoxidase (MPO) activity. The healing effects from MHs (200 mg/Kg) and diet with fruit pulp (10%) against gastric and duodenal ulcers induced by acetic acid were also evaluated by treating rats over 7 or 14 consecutive days of treatment.

Results

The phytochemical profile of MHs and fruit pulp indicated the presence of phenolic compounds (mainly flavonoids and condensed tannins). MHs (200 mg/Kg, p.o.) displayed an antidiarrheal effect and were able to protect gastric mucosa against absolute ethanol (68% protection) and also against the injurious effect of NSAIDs (86% protection) when compared to the group treated with vehicle. These results were accompanied by the prevention of GSH depletion and an inhibition of MPO activity when compared to animals treated with vehicle (P<0.05). MHs markedly protected duodenal mucosa against injuries caused by cysteamine (98%) and also against I/R induced gastric ulceration (80%) when compared to the group treated with vehicle. Furthermore, MHs also prevented the GSH depletion of gastric mucosa relative to the control group treated with vehicle. NO appeared to be involved in this gastroprotective effect. MHs and diet with fruit pulp clearly demonstrated gastric healing actions after treatment for 7 (MHs – 53% inhibition) or 14 days (MHs – 60% inhibition and fruit pulp – 61% inhibition). Treatment with diet with fruit pulp for 7 days demonstrates a significant duodenal healing effect (71% inhibition) without any signs of toxicity.

Conclusions

MHs clearly demonstrate antidiarrheal, gastroprotective and cicatrising effects in experimental gastric and duodenal ulcers, and the diet with fruit pulp displays duodenal healing effects. The observed effects may be associated with the antioxidant effect, which may be due the presence of condensed tannins and flavonoids in the bark and fruit of H. stigonocarpa.     

Evaluation of antiulcer activity of chromanone fraction from Calophyllum brasiliesnse Camb

Ethnopharmacological relevance

Calophyllum brasiliense Camb. (Clusiaceae), popularly known as ‘guanandi’, is found in the tropical areas and swampy lands. The latex exuding from its bark is used in the treatment of gastric ulcer in folk medicine. Several active compounds have been isolated from its stem bark among them, are the chromanone acids. Therefore, this study aimed to evaluate antiulcer activity and probable mechanism(s) of action of a fraction containing a mixture of chromanone acids (BI), derived by column chromatography fractionation of the hexane extract of the stem bark of Calophyllum brasiliense (HECb), using experimental in vitro and in vivo models.

Materials and methods

Ulcer was induced by oral administration of ethanol (75%, v/v) and indomethacin (50 mg/kg). Malondialdehyde, reduced glutathione and catalase activity was measured in stomach tissue after ethanol induced ulcer. In order to evaluate the effect of BI on nitric oxide, ulcer was induced by ethanol in l-NAME pretreated animals. Anti-Helicobacter pylori activity was verified in disk diffusion and broth microdilution in vitro assays, using cagA+ and vacA+ Helicobacter pylori strains.

Results

BI prevented the gastric ulceration caused by ethanol and indomethacin treatments. Its gastroprotective mechanism in ethanol-induced ulcer was partly due to reduction of MDA and CAT levels in the gastric tissue. BI did not affect the GSH levels and its gastroprotective effect was not reversed by pretreatment with l-NAME. BI showed anti-Helicobacter pylori in the both assays.

Conclusion

The results indicate that BI is partly responsible for the HECb antiulcer and anti-Helicobacter pylori effects.     

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.     

Fruit extracts of Momordica charantia potentiate glucose uptake and up-regulate Glut-4, PPARγ and PI3K

Ethnopharmacological relevance

Momordica charantia fruit is a widely used traditional medicinal herb as, anti-diabetic, anti-HIV, anti-ulcer, anti-inflammatory, anti-leukemic, anti-microbial, and anti-tumor.

Aims of study

The present study is undertaken to investigate the possible mode of action of fruit extracts derived from Momordica charantia (MC) and study its pharmacological effects for controlling diabetic mellitus. Effects of aqueous and chloroform extracts of Momordica charantia fruit on glucose uptake and up-regulation of glucose transporter (Glut-4), peroxisome proliferator activator receptor gamma (PPARγ) and phosphatidylinositol-3 kinase (PI3K), were investigated to show its efficacy as a hypoglycaemic agent.

Materials and methods

Dose dependent glucose uptake assay was performed on L6 myotubes using 2-deoxy-d-[1-³H] glucose. Up-regulatory effects of the extracts on the mRNA expression level of Glut-4, PPARγ and PI3K have been studied.

Results

The association of Momordica charantia with the aqueous and chloroform extracts of Momordica charantia fruit at 6 μg/ml has shown significant up-regulatory effect, respectively, by 3.6-, 2.8- and 3.8-fold on the battery of targets Glut-4, PPARγ and PI3K involved in glucose transport. The up-regulation of glucose uptake was comparable with insulin and rosiglitazone which was approximately 2-fold over the control. Moreover, the inhibitory effect of the cyclohexamide on Momordica charantia fruit extract mediated glucose uptake suggested the requirement of new protein synthesis for the enhanced glucose uptake.

Conclusion

This study demonstrated the significance of Glut-4, PPARγ and PI3K up-regulation by Momordica charantia in augmenting the glucose uptake and homeostasis.     

Evaluation of antiulcer activity and mechanism of action of methanol stem bark extract of Lafoensia pacari A. St.-Hil. (Lytraceae) in experimental animals

Ethnopharmacological relevance

Lafoensia pacari St.-Hil. is a tree native to the Brazilian Cerrado. Its bark macerate is popularly used in Brazilian folk medicine for the treatment of peptic ulcer, wound healing and inflammation.

Aim of the study

To evaluate the antiulcer activities of the methanol extract of Lafoensia pacari (MELP) and possible mechanisms of actions involved.

Materials and methods

The stem bark of Lafoensia pacari was macerated in methanol to obtain the crude methanol extract of Lafoensia pacari (MELP). The gastroprotective and ulcer healing of MELP were evaluated using ethanol, indomethacin, cold-restraint stress-induced (acute) and acetic acid (chronic) ulcer models. The probable mode of action of MELP was also evaluated by determining intestinal transit, involvement of non-protein sulfhyhydryls (NP-SH), gastric mucus secretion, gastric secretory parameters and pro-inflammatory cytokines, tumor necrosis factor-α (TNF-α) and interleukin-17 (IL-17). Phytochemical analysis was carried out using classical methods and ellagic acid, one of the most important pharmacological active compounds was confirmed by HPLC.

Results

The results of the pharmacological studies on MELP demonstrated potent and effective gastroprotection against ethanol, indomethacin and cold stress-induced acute ulcers and ulcer healing in acetic acid induced chronic ulcer. MELP had no significant effect on the intestinal motility and it is also independent of mucus production but rather have a mucolytic effect. In pylorus-ligated rats the extract showed anti-secretory activity by decreasing total gastric juice volume and gastric acidity while increasing the gastric pH. The gastroprotection against ethanol is partially attributed to effective attenuation in the decrease in NP-SH levels, inhibition of the increases in the pro-inflammatory cytokines, TNF-α and IL-17. Phytochemical analysis of MELP revealed the presence of pyrrogalic tannins, saponins, steroids, triterpenoids and simple phenols, with ellagic acid being the major components.

Conclusion

The results of this study showed that MELP possesses preventive and curative effects against gastric ulcer in experimental animals. These effects are partly dependent on its anti-oxidant, anti-secretory properties and inhibition of pro-inflammatory cytokines and independent of gastric/intestinal motility and mucus secretion. Ellagic acid, a compound of proven antiulcer activity, was found in MELP as the major component. These results confirmed the traditional use of MELP in Brazilian popular medicine for the treatment of gastric ulcers and shed some light on some of its mechanisms of action.     

Protective effect of Calotropis procera latex extracts on experimentally induced gastric ulcers in rat

Aim of the study

Calotropis procera is a wild growing plant with multifarious medicinal properties. The present study was carried out to evaluate the effect of dried latex (DL) of Calotropis procera and its methanol extract (MeDL) against gastric ulcers induced in rats.

Materials and methods

Aqueous suspension of DL (20 and 100 mg/kg) and MeDL (10 and 50 mg/kg) were given orally to 36 h fasted rats and ulcers were induced by ethanol, pyloric ligation and aspirin. Parameters like ulcer score and levels of oxidative stress markers were measured in all the models. The effect on gastric hemorrhage and tissue histology was studied in ethanol model and on acidity, pH and volume of gastric secretion was evaluated in pyloric ligation model. The protective effect of DL and MeDL was compared with that of standard anti-ulcer drug famotidine (20 mg/kg).

Results

DL and MeDL produced 85–95% inhibition of gastric mucosal damage in ethanol model and 70–80% inhibition in aspirin model. The protective effect of these extracts was associated with marked reduction in gastric hemorrhage, maintenance of tissue integrity and normalization of levels of oxidative stress markers like glutathione, thiobarbituric acid reactive substances and superoxide dismutase. Like famotidine, DL and MeDL decreased the gastric acidity from 376.17 ± 21.47 mequiv./l to 163.88 ± 6.86 and 201.48 ± 8.86 mequiv./l respectively in pyloric ligation model. These extracts increased the gastric pH without affording any protection to gastric mucosa in this model.

Conclusion

The latex of Calotropis procera has the therapeutic potential to relieve gastric hyperacidity and to prevent gastric ulceration induced by necrotizing agents.     

Evaluation of the antiulcerogenic activity profile of a flavonol diglucoside from Equisetum palustre L.

Ethnopharmacological relevance

The aerial parts of Equisetum palustre L. are used to treat peptic ulcer disease in Turkey. In a previous study, a flavonol diglucoside i.e., kaempferol 3-O-1″-β-d-glucopyranosyl-3-O-1″′-β-d-glucopyranoside (KGG) was isolated as the major antiulcerogenic constituent from the plant.

Aim of the study

The present study was undertaken to evaluate the antiulcer activity profile of KGG using various in vivo experimental ulcer models as well as by assessing gastric biochemical parameters.

Material and methods

KGG was obtained from the ethanol extract of the aerial parts of the plant by successive chromatographical methods. The activity profile of the compound was investigated using several ulcerogenesis models such as indomethacin-, indomethacin plus HCl/EtOH-, cysteamine-, serotonin-, N^G-nitro-l-arginine methyl ester plus EtOH-, diethyldithiocarbamate-, N-ethylmaleimide plus EtOH-, water immersion and restraint stress-, pyloric ligation-induced ulcers. In addition, effects of KGG on the biochemical parameters of gastric juice; i.e., inhibition of titratable gastric acidity, acid output, gastric pH, gastric secretion volume and peptic activity were studied.

Results

KGG exerted statistically significant gastroprotective activity against indomethacin-, indomethacin plus HCl/EtOH- and N-ethylmaleimide plus EtOH-induced ulcerogenesis. Moreover, KGG demonstrated weak activity against N^G-nitro-l-arginine methyl ester plus EtOH, water immersion and immobilization-induced stress, pyloric ligation-induced and diethyldithiocarbamate-induced gastric ulcer models, and also it was ineffective in the prevention of ulcers induced by serotonin and cysteamine. On the other hand, among the gastric biochemical parameters studied, KGG was only found to increase the gastric acid pH from 2.03 to 3.35.

Conclusion

Results of this investigation have clearly demonstrated that KGG was found to improve the cytoprotective mechanisms of the gastric mucosa. On the other hand, a weak activity profile was observed on the parameters affecting the gastric acidity (water immersion and restraint-induced-, pyloric ligation-induced-ulcerogenesis and titratable acidity).     

Gastroprotective effects of the essential oil of Hyptis crenata Pohl ex Benth. on gastric ulcer models

Ethnopharmacological relevance

Hyptis crenata Pohl ex Benth (Lamiaceae), popularly known as “hortelã-brava” or “hortelã do campo”, is widely distributed in the northeast of Brazil. In Brazil, the leaves of this plant have been used in traditional medicine for the treatment of gastrointestinal disturbances, including gastric ulcers. In an attempt to experimentally validate this claimed antiulcerogenic activity, the gastroprotective effects of the essential oil extracted from the leaves of the Hyptis crenata Pohl ex Benth (EOHc) were evaluated in recognized gastric ulcer models in mice.

Materials and methods

EOHc was obtained by hydrodistillation and analyzed using gas chromatography–mass spectrometry (GC–MS). Swiss male mice (25–30 g) were used for the studies. The gastric ulcers were induced by oral administration of absolute ethanol or indomethacin 45 min after oral pretreatment with EOHc, vehicle and positive control drugs. One hour after the ulcerative challenges, the stomachs were removed and the area of the lesions was measured. The volume, pH and total acidity of the gastric secretions were determined using the pylorus ligature model. The gastrointestinal motility was measured using gastric emptying and intestinal transit. The ethanol-induced gastric mucus depletion and lipid peroxidation were also analyzed.

Results

Our findings are as follows: A significant inhibition of gastric lesions induced by absolute ethanol was observed in the mice pre-treated with EOHc, at a dose of 30 and 100 and 300 mg/kg (5.56±1.51, 2.88±0.82 and 1.71±0.54 mm², respectively) compared to control group (118.03±35.4 mm²). Also, EOHc (300 mg/kg) produced a gastroprotective effect against the gastric lesions induced by indomethacin (16.07±4.68 mm²) compared to control group (38.64±6.1 mm²). EOHc pretreatment produced a reduction in the ethanol-induced lipid peroxidation from 3.9±0.22 to 2.4±0.1 μmol/mg tissue (EOHc-300 mg/kg and control group, respectively). We also observed that EOHc pretreatment decreased the gastric emptying, but did not alter the intestinal transit ratio, ethanol-induced depletion of the gastric wall mucus or secretion parameters (volume, pH and [H⁺]).

Conclusion

Our data indicate that EOHc exerts a gastroprotective effect, indicated by its significant inhibition of gastric lesions in ethanol- and indomethacin-induced ulcer models, which may be associated with its accelerating effect on gastric emptying and reduction in oxidative damages. Our data suggest a potential therapeutic application for EOHc in the treatment of gastric ulcers.     

Contribution to the ethnopharmacological and anti-Helicobacter pylori knowledge of Cyrtocarpa procera Kunth (Anacardiaceae)

Ethnopharmacological relevance

Cyrtocarpa procera Kunth (Anacardiaceae) is a Mexican endemic tree; its bark has been traditionally employed in Mexico since prehispanic times to relieve digestive disorders.

Aim of the study

To perform an acute evaluation of the toxicity, gastroprotective, and anti-inflammatory properties, as well as the anti-Helicobacter pylori action of C. procera bark extracts, in order to determine polypharmalcological activities.

Materials and methods

Five different polarity extracts (hexanic, CH₂Cl₂, CH₂Cl₂-MeOH, methanolic, and aqueous) were prepared. Each of them was evaluated in the following acute mice models: toxicity Lorke test, ethanol-induced gastric ulcer, TPA-induced ear edema; and the in vitro anti-H. pylori activity with a broth dilution method.

Results

None of the extracts were toxic under acute administration. The methanolic, hexanic, and aqueous extracts possess remarkable gastroprotective activity. All the extracts inhibit H. pylori growth, being the hexanic the most active, and only this one showed significant anti-inflammatory effect.

Conclusions

This work demonstrates that C. procera bark has polypharmacological activities; which makes it a promising asset to the development of an integral treatment for gastritis or peptic ulcer related or not to H. pylori. Our findings contribute to the ethnopharmacological knowledge about this species.     

Gastric antisecretory and antiulcer activities of Cyclea peltata (Lam.) Hook. f. & Thoms. in rats

Ethnopharmacological relevance

Cyclea peltata (Lam.) Hook. f. &; Thoms. (Menispermaceae), locally called ‘Padathaali/Padakizhangu’ is used in Ayurvedic medicine to treat peptic ulcer.

Aim of the study

To evaluate the gastric antisecretory and antiulcer activity of Cyclea peltata.

Materials and methods

The ethanolic extract of Cyclea peltata root was used to evaluate its gastric antisecretory and antiulcer effect in the pylorus-ligated rat model and gastric lesions induced by ethanol or ethanol and indomethacin respectively in rats. The levels of gastric wall mucus, non-protein sulfhydryl groups (NP-SH), malondialdehyde, protein and catalase activity in the stomach samples of Cyclea peltata treated and control groups of rats were also quantified.

Results

The ethanolic extract of Cyclea peltata roots showed significant antisecretory activity as evidenced by decreased pepsin secretion, gastric juice volume and acid output in pylorus-ligated rats. Pretreatment with Cyclea peltata extract provided significant protection against the peptic ulceration caused by ethanol administered individually, or in combination with indomethacin. Our studies also revealed that pretreatment with Cyclea peltata significantly increased the gastric protein and catalase concentration of ethanol treated rats. Further, it showed significant gastroprotective effects on the stomach wall of ethanol or ethanol and indomethacin treated rats by decreasing malondialdehyde level, increasing the gastric wall mucus and non-protein sulfhydryl groups.

Conclusion

The present findings demonstrate that Cyclea peltata ethanolic extract has potent antisecretory and antiulcer effects and justify the traditional/ethnic usage of this herb to treat peptic ulcers and consequent stomach ache.     

Antiulcerogenic action of ethanolic extract of the resin from Virola surinamensis Warb. (Myristicaceae)

Ethnopharmacological relevance

Virola surinamensis (Myristicaceae), popularly known as “mucuíba”, “ucuuba” or “ucuúba do igapó” is a large tree that grows abundantly in “Várzea” forest and on river banks in the Brazilian states of Amazonas and Tocantins. The resin obtained by cuts on the stem bark is a reputed folk remedy in its natural form for the treatment of ulcer, gastritis, inflammation and cancer.

Aim of the study

The present work evaluated the pharmacological activity of the resin obtained from bark of V. surinamensis as antiulcerogenic in experimental in vivo model in order to observe whether its traditional use is justified.

Materials and methods

The preventive action of ethanolic extract of V. surinamensis was evaluated in experimental in vivo models in rodents that simulated this disease in human gastric mucosa.

Results

Oral administration of acidified ethanol solution produced severe hemorrhagic lesions in glandular mucosa with ulcerative lesion of 50 ± 11.5 mm. In animals pretreated with V. surinamensis (500 mg/kg, p.o.) a significant inhibition of mucosal injury of 2.40 ± 0.56 mm (95% inhibition) was detected. The V. surinamensis, at the same dose, also reduced significantly (p < 0.05) the formation of gastric lesions induced by indomethacin (39%), stress (45%) and by pylorus ligature in mice (31%) when compared to animals treated with vehicle. The extract from V. surinamensis exerts gastroprotective action only when this extract contacts gastric mucosa (oral route) with increased pH values and reduced H⁺ concentration of gastric contents. The ethanolic extract of V. surinamensis resin was analyzed by TLC and spectrometric methods (NMR and ES-MS) and the main constituent of this extract was epicatechin.

Conclusions

We suggest that the epicatechin present in V. surinamensis resin may be among active principles responsible for the antiulcer activity shown by the tested resin but their used suggest carefulness because toxicological symptoms mentioned by population.     

Hyptis suaveolens (L.) Poit (Lamiaceae), a medicinal plant protects the stomach against several gastric ulcer models

Ethnopharmacological relevance

Hyptis suaveolens is used by the traditional population in several parts of the world to treat inflammation, gastric ulcer and infection and is used as a crude drug to relieve symptoms related with gastric ulcer or gastritis in northeaster and central region of Brazil.

Materials and methods

the standardized ethanolic extract (Hs-EtOHE) and hexanic fraction (Hs-HexF) of Hyptis suaveolens (62,5, 125, 250 and 500 mg/kg) was evaluated in several models of acute gastric ulcers. The participation of NO was evaluated by pretreatment with L-NAME and non-protein sulfyhydryls by NEM in the gastroprotective effect.

Results

Hs-EtOHE and Hs-HexF markedly reduced the gastric lesions induced by all ulcerogenic agents (HCl/ethanol, ethanol, NSAIDs and hypothermic restraint-stress). Gastric ulcerations were exacerbated by administration of NEM suggesting that the gastroprotective mechanism of action of Hs-EtOHE and Hs-HexF involves sulfhydryl groups.

Conclusion

Ours results show that an extract of Hyptis suaveolens, administered orally to rodents, present gastro protective activity in different models of acute of gastric ulcer and give some support to the reported claims on the use of this plant as a gastro protective agent.     

Antiulcer principle from Zingiber montanum

Ethnopharmacological relevance

Rhizome of Zingiber montanum has been extensively used as a folk medicine to ameliorate peptic ulcer at northern part of Bangladesh.

Aim of the study

To identify the antiulcer principle of the MeOH extract of the rhizome of Zingiber montanum by an ex vivo bioassay guided chromatographic separation and purification, and structure elucidation of the purified compound by spectroscopic methods.

Materials and methods

Dried powder of Zingiber montanum rhizomes was extracted with MeOH. The antiulcer activity of the crude extract and its chromatographic fractions were evaluated by the inhibition of 1 N HCl induced gastric lesions in Swiss albino mice. The pure compound was purified from the active fraction by crystallization with hexanes. Structure of the pure compound was elucidated by spectroscopic methods. The antiulcer activity of the pure compound was evaluated by the inhibition of 1 N HCl, 95% ethanol and indomethacin induced gastric lesions in mice.

Results

The MeOH extract of Zingiber montanum showed 61.97% and 83.10% inhibition of the 1 N HCl induced gastric lesions at doses of 200 mg/kg and 400 mg/kg, respectively, in mice. Chromatographic separation on silica gel of the extract was yielded seven fractions and the fraction 2 was found to have most potent antiulcer activity in mice. This fraction showed 77.46% inhibition of the 1 N HCl induced gastric lesions at a dose of 40 mg/kg in mice. Crystallization of the fraction yielded 1 (zerumbone, 180 mg). It showed statistically 45.77% and 92.25% inhibition of 1 N HCl induced gastric lesions in mice at doses of 20 mg/kg and 40 mg/kg, respectively. It also showed 29.07% and 45.35% inhibition of 95% ethanol induced gastric mucosal damage, and 64.76% and 72.38% inhibition of indomethacin induced gastric lesions in mice at doses of 20 mg/kg and 40 mg/kg, respectively.

Conclusion

Zerumbone (1) showed potent cytoprotective effect against necrotizing agent (HCl) and non-steroidal anti-inflammatory drug (indomethacin) induced gastric ulceration. It also exhibited moderate cytoprotective effect against noxious agent (EtOH) induced gastric lesions. It can be considered as a promising new antiulcer natural drug lead.     

Hancornia speciosa: indications of gastroprotective, healing and anti-Helicobacter pylori actions

Ethnopharmacological relevance

Mangaba (Hancornia speciosa Gomez) is a medicinal plant frequently cited in ethnopharmacological inventories of the central region of Brazil against gastrointestinal disorders such as diarrhoea, ulcer, gastritis and stomachache.

Aim of the study

The hydroalcoholic extract (HE) and infusion (BI) of Hancornia speciosa bark were investigated for their ability to prevent and heal rodent gastric ulcer.

Materials and methods

The preventive and healing action of both preparations of Hancornia speciosa were evaluated in experimental models in rodents that simulated this disease in human gastric mucosa.

Results

BI did not exert gastroprotective effect, in contrast to HE (500 mg/kg, p.o.) that decreased (p < 0.05) the severity of gastric damage induced by HCl/ethanol (52%), indomethacin/bethanechol (51%), stress (52%) or pylorus ligature experiments (54%). HE increased (p < 0.05) the pH and decreased acid output of gastric juice. This extract promoted increase of mucus amount (3.62 mg/wt. tissue vs. 5.81 mg/wt. tissue), healing action (67%) and displayed anti-Helicobacter pylori effect.

Conclusions

The antiulcer action of Hancornia speciosa resulted in increase of gastric mucus formation and antioxidant properties of polymeric proanthocyanidins present in the bark composition of this medicinal plant.     

Antioxidative action of methanolic extract and buthanolic fraction of Vochysia tucanorum Mart. in the gastroprotection

Aim of the study

Vochysia tucanorum is an important medicinal plant used in the Cerrado of Brazil against gastric disorders and this study reveals the pharmacological action of this traditional medicine use.

Materials and methods

The methanolic extract (E-MeOH) and buthanolic fraction (Fr-Bu) obtained from V. tucanorum were challenged by different necrotizing agents in rodents. NO-synthase inhibitor (L-NAME) and SH blocker (NEM) were used to evaluate the participation of cytoprotective factors in E-MeOH and Fr-Bu gastroprotection. Antiulcerogenic action of V. tucanorum was evaluated in rats and mice at doses 250, 500 or 1000 mg/kg (E-MeOH) and 37.5, 75 or 150 mg/kg (Fr-Bu).

Results

Both E-MeOH and Fr-Bu present elevated gastroprotective action in all in vivo experimental models, without signs of acute toxicity. The mechanisms involved in the gastroprotective action of E-MeOH and Fr-Bu are related to the antioxidant activity and protection to gastric mucosa NO levels. Phytochemical investigations of Fr-Bu identified different pentacyclic triterpenoids such as betulinic acid, erythrodiol, epi-betulinic acid and mixtures of ursolic acid and oleanolic acid derivatives as the major constituents. The presence of such triterpenoids in Fr-Bu is probably related to the potent gastroprotective action of this medicinal plant species.

Conclusion

Effectiveness in gastroprotection and the absence of acute toxicity indicate this species as a promising herbal drug that is in accordance with ethnopharmacological use against gastric disorders.     

Qualea parviflora Mart.: An integrative study to validate the gastroprotective,antidiarrheal, antihemorragic and mutagenic action

Ethnopharmacological relevance

Qualea parviflora Mart. is a medicinal species commonly found in the Brazilian Cerrado biome.

Aim of the study

Based on ethnopharmacological data, methanolic extract from Qualea parviflora (QP) bark was evaluated for its antiulcer, analgesic, anti-hemorrhagic, mutagenic and anti-Helicobacter pylori activities.

Material and methods

The gastroprotective action of the extract was evaluated in rodent experimental models (HCl/ethanol, ethanol or NSAID). We also evaluated mutagenic effect (Ames assay), anti-Helicobacter pylori, anti-hemorrhagic action, analgesic and inflammatory effects (hot-plate test and carrageenin-induced hind paw edema) of methanolic extract from Qualea parviflora.

Results

QP (500 mg/kg, p.o.) was able to protect gastric mucosa against HCl/ethanol solution (77%), absolute ethanol (97%), and also against injurious effect of NSAID (36%). When QP was challenged with sulfhydryl depletor compound, the gastroprotective action of extract was abolished. QP treatment was able to maintain the GSH level and show a concentration-dependent inhibition effect on the lipid peroxidation. QP present anti-Helicobacter pylori effect (MIC = 75 μg/mL), anti-hemorrhagic and antidiarrheal action but not present analgesic or anti-inflammatory effect.

Conclusion

methanolic extract from Qualea parviflora had gastroprotective effect related to the increase of gastric mucosa defensive factors such PGE₂ levels and maintain the basal gastric glutathione levels. The methanolic extract also showed anti-Helicobacter pylori activity, anti-hemorrhagic effect and antioxidant action, but absence of analgesic, mutagenic and toxic effects, a profile that adds safety to its use.     

Protective effects of Croton campestris A. St-Hill in different ulcer models in rodents: Evidence for the involvement of nitric oxide and prostaglandins

Ethnopharmacological relevance

Croton campestris A. St.-Hill., popularly known as “velame do campo”, is a species native from savannah area of Northeast Brazil, which is used by traditional communities in folk medicine for a variety of health problems, especially detoxification, inflammation and gastritis. The present study investigates the possible gastric antiulcer activity of Croton campestris root extract (CCRE) and mechanisms of action underlying this effect.

Materials and methods

Gastric lesions were induced in mice by ethanol, acidified ethanol and indomethacin. CCRE was previously administered orally in doses ranging from 50 to 750 mg/kg. Stomach lesions were measured. The involvement of Nitric Oxide (NO), prostaglandins (PGEs), ATP-dependent K+ channel and adrenergic receptor was investigated through specific inhibitors.

Results

CCRE produced significant antiulcer activity against absolute ethanol, acidified ethanol and indomethacin induced gastric lesions. The pretreatment with L-NAME (10 mg/kg, p.o.), an inhibitor of nitric oxide synthesis and indomethacin (10 mg/kg, s.c.), an inhibitor of prostaglandin production, reversed the antiulcer action of CCRE.

Conclusion

Taking together, these results suggest that the antiulcer activity of CCRE is dependent of NO and prostaglandin pathways possibly due to its ability to stimulate the synthesis of NO, and activation of endogenous prostaglandin production. Therefore, the use of CCRE in traditional Brazilian medicine against gastric disorders has a scientific basis.     

Effect of Mouriri pusa tannins and flavonoids on prevention and treatment against experimental gastric ulcer

Aim of the study

Mouriri pusa, popularly known as “manapuçá” or “jaboticaba do mato”, is a plant from Brazilian cerrado that has been found to be commonly used in the treatment of gastrointestinal disturbs in its native region. The present work was carried out to investigate the effect of tannins (TF) and flavonoids (FF) fractions from Mouriri pusa leaves methanolic extract on the prevention and cicatrisation process of gastric ulcers, and also evaluate possible toxic effects.

Materials and methods

The following protocols were taken in rats: acute assay, in which ulcers were induced by oral ethanol after pre-treatment with the fractions; and 14 days treatment assay, in which ulcers were treated for 14 days after induction by local injection of acetic acid.

Results

In the acute model, treatment with either, TF (25 mg/kg) or FF (50 mg/kg), was able to reduce lesion area, showing gastroprotective effect. In addition, FF proved itself anti-inflammatory by reducing COX-2 levels. In acetic acid model, both fractions exhibited larger ulcers’ regenerative mucosa, indicating cicatrisation enhancement. FF group also showed augmented cell proliferation, anti-inflammatory action and enhanced angiogenesis as well as increased mucus secretion. Moreover, concerning the toxicity parameters analyzed, no alteration in the fractions groups was observed.

Conclusions

Tannins and flavonoids from Mouriri pusa provide beneficial effects against gastric ulcers with relative safety.