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.

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.

Gastroprotective mechanisms of Citrus lemon (Rutaceae) essential oil and its majority compounds limonene and beta-pinene: Involvement of heat-shock protein-70, vasoactive intestinal peptide, glutathione, sulfhydryl compounds, nitric oxide and prostaglandin E-2

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

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

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

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

Ethnopharmacological relevance: Virola surinamensis (Myristicaceae), popularly known as mucuiba, ucuuba or ucuuba do igapo is a large tree that grows abundantly in Varzea 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. (C) Published by Elsevier B.V.

Morphologic and Pharmacological Investigations in the Epicatechin Gastroprotective Effect

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Angiotensin II, progesterone, and prostaglandins are sequential steps in the pathway to bovine oocyte nuclear maturation

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Paracoccidioides brasiliensis Uses Endogenous and Exogenous Arachidonic Acid for PGE(x) Production

Paracoccidioides brasiliensis is the agent of paracoccidioidomycosis, the most prevalent deep mycosis in Latin America. Production of eicosanoids during fungal infections plays a critical role on fungal biology as well as on host immune response modulation. The purpose of our study was to assess whether P. brasiliensis strains with different degree of virulence (Pb18, Pb265, Bt79, Pb192) produce prostaglandin E-x (PGE(x)). Moreover, we asked if P. brasiliensis could use exogenous sources of arachidonic acid (AA), as well as metabolic pathways dependent on cyclooxygenase (COX) enzyme, as reported for mammalian cells. A possible association between this prostanoid and fungus viability was also assessed. Our results showed that all strains, independently of their virulence, produce high PGE(x) levels on 4 h culture that were reduced after 8 h. However, in both culture times, higher prostanoid levels were detected after supplementation of medium with exogenous AA. Treatment with indomethacin, a COX inhibitor, induced a reduction on PGEx, as well as in fungus viability. The data provide evidence that P. brasiliensis produces prostaglandin-like molecules by metabolizing either endogenous or exogenous AA. Moreover, the results suggest the involvement of these mediators on fungal viability.

Hyperalgesic and edematogenic effects of peptides isolated from the venoms of honeybee (Apis mellifera) and neotropical social wasps (Polybia paulista and Protonectarina sylveirae)

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

Indole ring oxidation by activated leukocytes prevents the production of hypochlorous acid

Hypochlorous acid (HOCl) released by activated leukocytes has been implicated in the tissue damage that characterizes chronic inflammatory diseases. In this investigation, 14 indole derivatives, including metabolites such as melatonin, tryptophan and indole-3-acetic acid, were screened for their ability to inhibit the generation of this endogenous oxidant by stimulated leukocytes. The release of HOCl was measured by the production of taurine-chloramine when the leukocytes (2 x 10(6) cells/mL) were incubated at 37ºC in 10 mM phosphate-buffered saline, pH 7.4, for 30 min with 5 mM taurine and stimulated with 100 nM phorbol-12-myristate acetate. Irrespective of the group substituted in the indole ring, all the compounds tested including indole, 2-methylindole, 3-methylindole, 2,3-dimethylindole, 2,5-dimethylindole, 2-phenylindole, 5-methoxyindole, 6-methoxyindole, 5-methoxy-2-methylindole, melatonin, tryptophan, indole-3-acetic acid, 5-methoxy-2-methyl-3-indole-acetic acid, and indomethacin (10 µM) inhibited the chlorinating activity of myeloperoxidase (MPO) in the 23-72% range. The compounds 3-methylindole and indole-3-acetic acid were chosen as representative of indole derivatives in a dose-response study using purified MPO. The IC50 obtained were 0.10 ± 0.03 and 5.0 ± 1.0 µM (N = 13), respectively. These compounds did not affect the peroxidation activity of MPO or the production of superoxide anion by stimulated leukocytes. By following the spectral change of MPO during the enzyme turnover, the inhibition of HOCl production can be explained on the basis of the accumulation of the redox form compound-II (MPO-II), which is an inactive chlorinating species. These results show that indole derivatives are effective and selective inhibitors of MPO-chlorinating activity.

Anti-inflammatory and analgesic potential of hydrolyzed extract of Agave sisalana Perrine ex Engelm., Asparagaceae

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

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.

EFFECTS OF ENDOTOXIN, INTERLEUKIN-1-BETA AND PROSTAGLANDIN INJECTIONS ON FEVER RESPONSE IN BROILERS

1. The effect of endotoxin, interleukin-1 beta and prostaglandin on fever response was studied in 80 broilers (Hubbard strain). Endotoxin (E. coli, LPS) was injected iv (1.5 mu g/kg) and icv (1.5 mu g/bird); interleukin-1 (human recombinant IL-1 beta, 80 pg/bird) and prostaglandin E(2) (5 mu g/bird) were injected icv. Indomethacin (10 mg/kg, iv) pretreatment was also used before iv endotoxin injection. 2. The results showed that indomethacin was able to block the fever response induced by iv endotoxin injection, and IL-1 beta and PGE(2) were both effective in producing fever when injected icv. These data suggest a prostaglandin-mediated fever response by broilers, and also a strong evidence of the involvement of endogenous pyrogen (interleukin-1) in fever response in birds.

Pharmacological modulation of allergic inflammation in the rat airways and association with mast cell heterogeneity

Administration of ovalbumin by aerosol to sensitised rats produced a rapid (15 min) protein exudation in different airway tissues, as determined by Evans blue staining. This was associated with marked mast cell degranulation determined by histological examination, with there being no difference between mucosal and connective tissue mast cells. A 5-day administration regimen with compound 48/80 selectively depleted connective tissue mast cell (Positive to berberine staining) without modifying ovalbumin-induced plasma protein extravasation. Treatment of rats with dexamethasone (1 mg/kg, - 12 h) or nor-dihydroguaiaretic acid (30 mg/kg i.p., - 30 min) significantly reduced ovalbumin-induced protein extravasation and preserved mucosal mast cell morphology. Indomethacin (4 mg/kg i.v., - 30 min) exerted no effect on either parameter. In conclusion, we propose the mucosal mast cell as a target cell responsible at least partly for the inhibitory actions of known anti-inflammatory drugs. We suggest an involvement of endogenous leukotriene(s), but not prostanoid(s), in mucosal mast cell activation/degranulation. (C) 2001 Published by Elsevier B.V. B.V.

Effects of tea from Turnera ulmifolia L. on mouse gastric mucosa support the Turneraceae as a new source of antiulcerogenic drugs

Turnera ulmifolia is a plant belonging to the family Turneraceae, popularly known in Brazil as chanana. This species is distributed from Guyana to southern Brazil where it is considered a weed. The plant occurs in tropical rain forest, fields, and gardens. Chanana tea is used in Brazilian folk medicine for the treatment of diseases related mainly to gastric dysfunction including gastric and duodenal ulcers. In this study, the ability of a lyophilized infusion, as an aqueous fraction (AqF) of the aerial parts of T. ulmifolia, was investigated for its ability to prevent ulceration of the gastric and duodenal mucosa was examined in mice and rats, respectively. The AqF significantly reduced the formation of lesions associated with HCl/ethanol administration by 39% and 46%, respectively, at doses of 500 mg/kg and 1000 mg/kg, p.o. The AqF also significantly reduced the incidence of gastric lesions induced by a combination of indomethacin and bethanechol by 58% and 72% at doses of 500 mg/kg and 1000 mg/kg, respectively. In stress-induced gastric ulcer, the inhibition by the AqF was 48%, 57%, and 58% at doses of 250 mg/kg, 500 mg/kg, and 1000 mg/kg, respectively (p<0.05). A pyloric ligature experiment showed that the highest dose of the AqF significantly affected the gastric juice parameters by increasing the pH from 2.5 (control) to 5.3 and decreasing the acid output from 11.3 (control) to 3.7 mEq/ml/4 h. The AqF had no significant effect on duodenal ulcers induced by cysteamine. Preliminary phytochemical screening confirmed that flavonoids were the major constituents of the AqF of T. ulmifolia. These results indicate that this extract has a significant antiulcerogenic effect, as popularly believed.