Healing, antioxidant and cytoprotective properties of Indigofera truxillensis in different models of gastric ulcer in rats.

The present study evaluated the antiulcerogenic activity and mechanisms of the aqueous (AqF 100 mg/kg) and ethyl acetate (AcF 50 mg/kg) fractions from Indigofera truxillensis leaves. This dose was selected to assess its activity on ulcer healing and its action on gastric acid and mucus secretion, prostaglandin production and antioxidant enzyme activity (superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and glutathione reductase (GSH-Rd)). Gastric ulcer was induced by absolute ethanol. Antisecretory action, mucus and prostaglandin production, healing and antioxidant enzyme activities were evaluated for both fractions. AqF and AcF significantly inhibited the gastric mucosal damage caused by ethanol. This effect was statistically significant at 100 and 50 mg/kg compared with the vehicle. Neither fraction interfered with gastric secretion. AcF increased the PGE(2) production, and both fractions increased mucus production. l-NAME did not alter the gastroprotection exerted by the fractions, but N-ethylmaleimide attenuated only AcF. In the ischemia/reperfusion model both fractions inhibited the mucosal damage. AcF increased SOD, GSH-Px and GSH-Rd activity, but AqF increased only SOD and GSH-Px. In the acetic acid-induced ulcer model AcF only accelerated ulcer healing. These results showed that Indigofera truxillensis acted as a gastroprotective agent, stimulating protective factors and antioxidants enzymes.

Indigofera suffruticosa Mill as new source of healing agent: involvement of prostaglandin and mucus and heat shock proteins.

ETHNOPHARMACOLOGICAL RELEVANCE: Indigofera suffruticosa is specie typical of the "Cerrado" or Brazilian savannah; it is a member of the Fabaceae family - in folkmedicine is used for gastric disorders, infection and inflammation. AIM OF THE STUDY: Ethyl acetate fraction (AcF) and aqueous fraction (AqF) of the methanolic extract of I. suffruticosa leaves were evaluated against acute gastric ulcer. The AcF fraction was selected to assess its activity in ulcer healing and its gastroprotective effects via mucus and gastric secretion. MATERIALS AND METHODS: The gastroprotective action of AcF and AqF fractions were evaluated in a rodent experimental model. The action mechanisms, involvements of the antisecretory action, mucus and prostaglandin production, toxicological and healing activity of the AcF (100mg/kg, p.o.) were evaluated. We also used histological analysis (HE and PAS) and immunohistochemical (PCNA and HSP-70) assays to evaluate the effects of I. suffruticosa. RESULTS: AcF significantly inhibited the gastric mucosal damage caused by ethanol. This effect was statistically significant in 100mg/kg group compared vehicle. AcF did not interfered with gastric secretion, significantly increased the PGE(2) and mucus production (validated in PAS technique). The gastroprotection was attenuated by pretreatment with N-ethylmaleimide, but not L-NAME. In acid-acetic-induced ulcer model AcF accelerated ulcer healing. Immunohistochemistry analysis showed induction of proliferating cell (PCNA) and heat shock protein (HSP 70). CONCLUSIONS: These results showed that AcF acted as gastroprotective agent stimulating prostaglandin, mucus and HSP70.

Mechanisms of the gastric antiulcerogenic activity of Anacardium humile St. Hil on ethanol-induced acute gastric mucosal injury in rats.

Leaves and bark infusions Anacardium humile St. Hil. (Anacardiaceae), known as in Brazil as "cajuzinho do cerrado", have been used in folk medicine as an alternative treatment for ulcers and gastritis. This study evaluated the gastroprotective activity of an ethyl acetate extract of the leaves of A. humile (AcF) and the mechanism involved in this gastroprotection. Pretreatment concentrations (50, 100, 200 mg x kg⁻¹) were administered by gavage. Following a 60 min. period, all the rats were orally administered 1 mL of absolute ethanol. One hour after the administration of ethanol, all groups were sacrificed, and the gastric ulcer index was calculated. Prostaglandin PGE2 concentration, gastric adherent mucous, and the participation of nitric oxide (NO) and sulfhydryl compounds in the gastroprotection process were also analyzed using the most effective tested dose (50 mg x kg⁻¹). A histological study of the glandular stomach for the evaluation of the epithelial damage and mucus content was also performed. AcF significantly reduced the gastric damage produced by ethanol. This effect was statistically significant for the 50 mg x kg⁻¹ group compared to control. Also, it significantly increased the PGE2 (by 10-fold) and mucous production, while pretreatment with NG-nitro-L-arginine methyl ester (L-NAME) or N-ethylmaleimide (NEM) completely abolished the gastroprotection. AcF has a protective effect against ethanol, and this effect, might be due to the augmentation of the protective mechanisms of mucosa.

Gastroprotective activity of ferruginol in mice and rats: effects on gastric secretion, endogenous prostaglandins and non-protein sulfhydryls.

The gastroprotective mechanism of the natural diterpene ferruginol was assessed in mice and rats. The involvement of gastric prostaglandins (PGE(2)), reduced glutathione, nitric oxide or capsaicin receptors was evaluated in mice either treated or untreated with indometacin, N-ethylmaleimide (NEM), N-nitro-L-arginine methyl ester (L-NAME) or ruthenium red, respectively, and then orally treated with ferruginol or vehicle. Gastric lesions were induced by oral administration of ethanol. The effects of ferruginol on the parameters of gastric secretion were assessed in pylorus-ligated rats. Gastric PGE(2) content was determined in rats treated with ferruginol and/or indometacin. The reduction of gastric glutathione (GSH) content was determined in rats treated with ethanol after oral administration of ferruginol, lansoprazole or vehicle. Finally, the acute oral toxicity was assessed in mice. Indometacin reversed the gastroprotective effect of ferruginol (25 mg kg(-1)) but not NEM, ruthenium red or L-NAME. The diterpene (25 mg kg(-1)) increased the gastric juice volume and its pH value, and reduced the titrable acidity but was devoid of effect on the gastric mucus content. Ferruginol (25, 50 mg kg(-1)) increased gastric PGE(2) content in a dose-dependent manner and prevented the reduction in GSH observed due to ethanol-induced gastric lesions in rats. Single oral doses up to 3 g kg(-1) ferruginol did not elicit mortality or acute toxic effects in mice. Our results showed that ferruginol acted as a gastroprotective agent stimulating the gastric PGE(2) synthesis, reducing the gastric acid output and improving the antioxidant capacity of the gastric mucosa by maintaining the GSH levels.

Should Anacardium humile St. Hil be used as an antiulcer agent? A scientific approach to the traditional knowledge.

The crude methanolic extract (ME) obtained from the leaves of Anacardium humile was evaluated orally at doses of 250-500-1000 mg/kg on gastric lesion on ethanol and piroxicam induced gastric lesions in rodents. All the tested doses significantly inhibited gastric lesions by 56 to 100%. These results seems to support the traditional use of this species in the treatment of gastric diseases.

Antioxidant activity of indigo and its preventive effect against ethanol-induced DNA damage in rat gastric mucosa.

Ethanol-induced oxidative damage is commonly associated with the generation of reactive oxygen molecules, leading to oxidative stress. Considering that antioxidant activity is an important mechanism of action involved in cytoprotection, the aim of this work was to evaluate the antioxidant properties of the alkaloid indigo (1) (2 mg/kg, P. O.), obtained from the leaves of Indigofera truxillensis Kunth (Fabaceae), on rat gastric mucosa submitted to ethanol-induced (100%, 1 mL, P. O.) gastric ulcer. Enzymatic assays and DNA fragmentation analysis were performed. When ethanol was administered to the control group, the sulfhydryl content (SH) and the glutathione peroxidase (GPx) activity decreased by 41% and 50%, respectively; in contrast, superoxide dismutase (SOD) and glutathione reductase (GR) activities increased by 56% and 67%, respectively. Additionally, myeloperoxidase (MPO) activity, a marker for free radical generation caused by polymorphonuclear neutrophil (PMN) tissue infiltration, also increased 4.5-fold after ethanol treatment. Rat gastric mucosa exposed to ethanol showed DNA fragmentation. Indigo alkaloid pretreatment protected rats from ethanol-induced gastric lesions. This effect was determined by the ulcerative lesion area (ULA), indicating an inhibition of around 80% at 2 mg/kg. This alkaloid also diminished GPx activity, which was higher than that observed with ethanol alone. However, this effect was counterbalanced by increased GR activity. Indigo was unable to restore alterations in SOD activity promoted by ethanol. After indigo pretreatment, SH levels and MPO activity remained normal and gastric mucosa DNA damage caused by ethanol was also partially prevented by indigo. These results suggest that the gastroprotective mechanisms of indigo include non-enzymatic antioxidant effects and the inhibition of PMN infiltration which, in combination, partially protect the gastric mucosa against ethanol-induced DNA damage.

Vernonia polyanthes as a new source of antiulcer drugs.

Methanolic (VPME) and chloroformic (VPCL) extracts, obtained from the aerial parts of Vernonia polyanthes, were investigated for its antiulcerogenic properties. Administration of VPME (250 mg/kg) and VPCL (50 mg/kg) significantly inhibited the gastric mucosa damage (64% and 90%, respectively) caused by absolute ethanol (p.o.). Otherwise, in NSAID-induced gastric damage, their gastroprotective effects have decreased. Since the VPCL extract resulted to be more effective than the VPME we focused our efforts over VPCL action mechanism of action.

Antiulcerogenic activity of Indigofera truxillensis Kunth / Atividade altiulcerogênica de Indigofera truxillensis Kunth

The genus Indigofera (Fabaceae) is used in folk medicine to treat gastrointestinal pain. In this study, we investigated the antiulcerogenic properties of Indigofera truxillensis Kunth. Oral administration of MeOH extract did not produce any signals of acute toxicity. The antiulcerogenic activity was assessed in different models of acute gastric ulcers (100 percent ethanol, piroxicam 30 mg.kg-1, hypothermic restraint stress and pylorus ligature) in mice and rats. The animals were treated with the drugs lanzoprazole (30 mg.kg-1) or cimetidine (100 mg.kg-1) as positive controls depending on the performed model. In another experiment with ethanol-induced ulcers in rats, N-ethylmaleimide (NEM), a sulfhydryl group blocker, was also used. The MeOH extract, at doses of 250, 500 and 1000 mg.kg-1, inhibited the gastric lesions in all experiments: a) by 62 percent, 69 percent and 32 percent, respectively, in piroxicam-induced lesions, b) by 43 percent, 71 percent and 98 percent, in ethanol-induced lesions, c) by 69 percent, 64 and 89 percent, in hypothermic-restraint stress-induced lesions, d) by 73 percent, 82 percent and 84 percent, in pylorus ligature lesions. Significant changes in the total gastric acid levels were also found after intraduodenal administration of the MeOH extract in the ligated pylorus model. Pre treatment with NEM reduced partially the antiulcerogenic activity of the MeOH extract in ethanol-induced gastric lesions. This result indicates an increase in the levels of non-protein sulfhydryl groups by MeOH extract in the gastric mucosa. These results indicate that the MeOH extract has antisecretory and citoprotective effects that may be related to the presence of flavonoids detected by phytochemical analysis.

O gênero Indigofera (Fabaceae) é utilizado na medicina tradicional para distúrbios gastrintestinais. Em nosso trabalho foi investigada a propriedade antiulcerogênica da Indigofera truxillensis Kunth. A administração oral do extrato metanólico (MeOH) não produziu efeitos tóxicos. A atividade antiulcerogênica foi avaliada em diferentes modelos agudos de úlcera gástrica (etanol 100 por cento, piroxicam 30 mg.kg-1, estresse por retenção e frio e ligadura do piloro) em camundongos e ratos. Os animais foram tratados com lansoprazol (30 mg.kg-1) ou cimetidina (100 mg.kg-1), que foram utilizados como controle positivo dependendo do modelo testado. Em outro experimento com úlcera induzida por etanol em ratos, N-etilmaleimida (NEM), um bloqueador dos compostos sulfidríla, também foi utilizado. O extrato metanólico, nas doses de 250, 500 e 1000 mg.kg-1, inibiu significativamente as lesões gástricas em todos os experimentos: a) 62 por cento, 69 por cento e 32 por cento, respectivamente, nas lesões gástricas induzidas por piroxicam, b) 43 por cento, 71 por cento e 98 por cento, nas lesões gástricas induzidas por etanol, c) 69 por cento, 64 por cento e 89 por cento, nas lesões gástricas induzidas por estresse por contenção e frio, d) 73 por cento, 82 por cento e 84 por cento, nas lesões gástricas induzidas por ligadura de piloro. Alterações significativas foram observadas na concentração total de ácido gástrico após a administração via intraduodenal do extrato MeOH no modelo de ligadura do piloro. Pré-tratamento com NEM reduziu parcialmente a atividade antiulcerogênica do extrato MeOH na úlcera induzida por etanol, o que sugere um aumento nos níveis de compostos sulfidríla pelo extrato MeOH na mucosa gástrica. Os resultados indicam que o extrato MeOH possui um efeito antisecretor e citoprotetor, e que tais efeitos podem estar relacionados com a presença de flavonóides detectados por análise fitoquímica no extrato MeOH.