Effect of hydroalcoholic extract of Zingiber officinalis rhizomes on LPS-induced rat airway hyperreactivity and lung inflammation.

Ginger, the rhizome of Zingiber officinalis Roscoe (Zingiberaceae), is a common constituent of diets around the world and its extracts have been reported to exhibit several pharmacological activities. We investigated the effect of crude hydroalcoholic extract of ginger on the rat trachea hyperreactivity (RTHR) and lung inflammation induced by lipopolysaccharide (LPS). Our results demonstrate that ginger extract and celecoxib attenuated RTHR 90 min and 48 h after LPS. Ginger and celecoxib reduced the serum level of prostaglandin (PGE2) and thromboxane (TXA2) 90 min after LPS. Celecoxib and ginger also reduced myeloperoxidase activity and the number of cells in rat bronchoalveolar lavage 48 h post-LPS. On lung parenchyma, ginger and celecoxib reduced the release of PGE2 and TXA2 48 h post-LPS. These results suggest that ginger exerts an anti-inflammatory effect on lung attenuating RTHR and COX metabolites seem to be involved in these processes.

Characterization of trace elements in Casearia medicinal plant by neutron activation analysis.

Leaves of Casearia sylvestris, Casearia decandra and Casearia obliqua plant species, collected at the Atlantic Forest in Brazil, were analyzed by using instrumental neutron activation analysis (INAA). Short and long irradiations using thermal neutron flux of the IEA-R1 nuclear reactor were carried out for these analyses. Concentrations of Ca, K and Mg were found in these samples at the percentage levels, Br, Cl, Fe, Mn, Na, Rb and Zn at the microg g(-1) levels and Co, Cr, Cs, La, and Sc at the microg kg(-1) levels. Comparisons were made among the element concentrations obtained in these three Casearia species and significant differences were found for the elements Cl, Co, Cs, Cr, La, Mn, Na and Sc. The precision and the accuracy of the results were evaluated by analyzing the certified reference materials NIST-1515 Apple Leaves and NIST-1573a Tomato Leaves.

Pharmacological assay of Cordia verbenacea V: oral and topical anti-inflammatory activity, analgesic effect and fetus toxicity of a crude leaf extract.

Cordia verbenacea D.C. (Borraginaceae) is a perennial bush plant that grows widely along the southeastern coast of Brazil. Its leaves have been used in folk medicine for their anti-ulcer, anti-inflammatory and cicatrizing activities. We have already described the anti-inflammatory properties of C. verbenacea and its low toxicity in different acute animal models. In the present study, we investigated the anti-inflammatory activity in sub-chronic animal models of a crude leaf lyophilized extract when administered by oral route or topically applied, and concomitantly, its analgesic potency and toxicity to the fetus. Topical administration of the extract inhibited nystatin-induced edema proportionally to the doses used, and this effect at a dose of 4.56 mg/kg body wt. was similar to that observed with 6.0 mg/kg body wt. of naproxen. In miconazole-induced edema, the leaf extract at a dose of 1.24 mg/kg body wt., orally administered, has a very similar effect as compared to nimezulide (2.5 mg/kg body wt.) and dexamethasone (0.2 mg/kg body wt.). At an oral dose of 2.48 mg/kg body wt. the extract showed a very low analgesic effect, and total absence of fetus toxicity at doses of less than 7.44 mg/kg body wt.

Anti-inflammatory effect of the hydralcoholic extract of Zingiber officinale rhizomes on rat paw and skin edema.

Plant extracts have been used for centuries as a popular mode of treatment for several health disorders. Over the last ten years, the study of those extracts has attracted attention in different fields of the biological sciences. Ginger, the rhizome of Zingiber officinale Roscoe (Zingiberaceae), is a commom constituent of diet worldwide and it has been reported that its extracts present some pharmacological activities. Here we investigate the effects of the crude hydralcoholic extract of ginger rhizomes on the classical models of rat paw and skin edema. The carrageenan-, compound 48/80- or serotonin-induced rat paw edema were inhibited significantly by the intraperitoneal administration of alcoholic ginger extract. Ginger extract was also effective in inhibiting 48/80-induced rat skin edema at doses of 0.6 and 1.8 mg/site. Rat skin edema induced by substance P or bradikinin was not affected by treatment with Z. officinalle extract. The intraperitoneal administration of ginger extract (186 mg/kg(-1) body wt.) 1 h prior to serotonin injections, reduced significantly the serotonin-induced rat skin edema. Our results demonstrated that crude extract of Zingiber officinale was able to reduce rat paw and skin edema induced by carrageenan, 48/80 compound and serotonin. The antiedematogenic activity seems to be related, at least partially, to an antagonism of the serotonin receptor.

The anti-inflammatory and analgesic effects of a crude extract of Petiveria alliacea L. (Phytolaccaceae).

Petiveria alliacea L (Phytolaccaceae) is a perennial bush plant that grows widely in Brazil. The roots and leaves of P. alliacea have been used in folk medicine for their antispasmodic, sedative, diuretic and antihelminthic actions. We recently described the anti-inflammatory properties of P. alliacea administered topically and orally in different animal models. In the present study, we investigated the anti-inflammatory activity of a crude lyophilized extract of P. alliacea roots administered to rats with pleurisy. The oral administration of P. alliacea root extract did not significantly reduce the total number of leukocytes at the doses tested. By contrast, the highest dose of extract tested (43.9 mg/kg body wt.) significantly reduced the number of migrating neutrophils, mononuclear cells and eosinophils; the dose of 31.4 mg/kg body wt. also reduced mononuclear cell migration. The P. alliacea root extract also showed a significant analgesic effect in the experimental model used. The results of this study provide a basis for the use of P. alliacea extracts in popular folk medicine, but further studies are necessary to elucidate the mechanism of its anti-inflammatory and analgesic actions.

Antiulcer action of the hydroalcoholic extract and fractions of Davilla rugosa Poiret in the rat.

Davilla rugosa Poiret ("Cipó- Caboclo") is commonly used in Brazilian folk medicine. The hydroalcoholic extract of the stems (HE) was fractionated with chloroform (CF), chloroform/ethyl acetate (CAF), ethyl acetate (AF), ethyl acetate/ethanol (AEF), ethanol (EF), and ethanol/water (EWF). The hydroalcoholic extract (HE) and fractions of the stems of D. rugosa Poiret were investigated for possible anti gastric ulcer properties. These extracts were shown to protect rats from developing gastric ulcers induced by two acute models: HCl/ethanol (400 mg/kg i.p.) and immersion-restraint stress (15 and 30 mg/kg of the HE and 15 mg/kg either of the ethanol or the ethanol/water fractions, p.o.). The daily oral dose of 800 mg/kg of HE for 30 consecutive days was tested for possible toxic effects. There were no modifications in body weight, water or food intake or in the external aspect of kidneys, spleen, lungs and liver. The only difference observed was a decrease of liver weight. These results suggest that the D. rugosa Poiret HE has an antiulcer activity in rats and the active components are in the two more polar fractions.

Synthesis and characterization of a diruthenium-ibuprofenato complex comparing its anti-inflammatory activity with that of a copper(II)-ibuprofenato complex.

The ibuprofen complex of diruthenium(II,III) was prepared and characterized by electronic (UV-Vis) and vibrational (FTIR) spectroscopies and thermogravimetry. The copper(II)-ibuprofenato complex was prepared by a different route from that described in the literature. Both complexes were tested in vivo for anti-inflammatory activity. Oral administration of the two complexes inhibited development of carrageenin-induced edema in rats, this inhibition being similar to that observed for oral administration of the parent drug (free ibuprofen). However, gastric irritation was lower as compared to that of ibuprofen. Diruthenium-ibuprofenato exhibited a protective effect at light intensity ulceration while the copper-ibuprofenato complex was more effective in the protection of severe intensity ulceration.

Antiulcer activity of the crude extract from the leaves of casearia sylvestris.

In rats, administration of Casearia sylvestris extract derived from fresh and dried leaves protects stomach mucosa without changing gastric pH. In stress-induced acute lesions, the preventive effect of extract from dried leaves is more effective than extract from fresh leaves. In acetic acid-induced chronic ulcer, both extracts reduce the size of ulceration and increase the number of collagen fibers after 5 days of treatment, and these effects are similar with both extracts. These antiulcer activities of Casearia sylvestris may be due to the presence of volatile oils, tannins and triterpenerelated compounds.

Antiulcer action of Microgramma squamulosa (Kaulf.) Sota.

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

Anti-inflammatory activity of the crude extract from the fruits of Pterodon emarginatus Vog.

The vegetal species Pterodon emarginatus Vog. (Leguminosae/Papilonaceae), popularly known in Brazil as 'sucupira branca', is widely used by domestic medicine as an anti-inflammatory. From these observations, the hexanic crude extract (HCE) of the fruits was obtained and submitted for assessment of its anti-inflammatory activity. For this purpose, the following tests were used: (1) Determination of ED50 and LD50; (2) Paw edema induced by carrageenin, dextran, histamine and nystatin; (3) Peritonitis caused by carrageenin and (4) Granuloma test. The ED50 (oral) in the edema induced by carrageenin was 500 mg/kg, and LD50 (oral) was 4.02 g/kg. In the edema caused by nystatin, there was a significant inhibition by 45% (P < 0.05 student's t-test) at the 6th hour following the treatment. In the granuloma test performed in animals treated with HCE, there was an inhibition of the granulomatous tissue formation by 22%. The migration of neutrophils towards the peritoneal cavity was inhibited in HCE treated animals by 43% (P < 0.05). However, in the edema caused by dextran and histamine, there was no significant response in HCE treated animals.

Miconazole as inflammatory agent. II: Time course of pleurisy and drug interference.

1. Miconazole-induced pleurisy was characterized by edema development and leukocyte infiltration. 2. This response was inhibited by chlorpheniramine, methysergide and steroidal and nonsteroidal anti-inflammatory drugs. 3. After miconazole injection, no mast cells were found in the pleural cavity. 4. Our results support the concept that biogenic amines released from mast cells and cyclooxygenase-derived mediators may contribute to the pathogenesis and evolution of miconazole inflammation.

Antiulcer action and toxicity of Styrax camporum and Caesalpinia ferrea.

Oral administration of Styrax camporum Pohl and Caesalpinia ferrea Martius stem extracts, atropine, and cimetidine, during 15 days, decreased the ulceration size, gastric secretion volume, and increased collagen fibre number of chronic ulcer induced by acetic acid in rats. The pH increased and the concentration of hydrochloric acid decreased after administration of atropine and cimetidine. The ethyl acetate fraction, obtained by chromatography from Styrax camporum Pohl extracts, showed antiulcer activity. The subchronic toxicity was studied during 30 days, through weight variation, water and food consumption and spleen, lung, kidney and liver relative weights. No difference to the control-lot was observed.

Lymphatic mast cell response and effect of compound 48/80 on popliteal lymph node reaction in rats following intracutaneous injection of Staphylococcus aureus.

To investigate the significance of mast cells in the popliteal lymph node during the development of an inflammatory response, rats were inoculated with 12 x 10(7) colony-forming units of Staphylococcus aureus in the hind foot pad. Numerical changes in mast cells were then measured in the corresponding popliteal lymph node. Six days after inoculation, despite the enlargement of the responding lymph node, a marked decrease in granulated mast cell number, relative to the contralateral node, was observed in the cortical and medullary compartments. Popliteal lymph nodes from rats treated with compound 48/80 and then inoculated with S. aureus showed a higher cortical and medullary hypertrophic response and a significant increase in degranulated/weakly basophilic mast cell number in the lymph node tissue. The findings suggest that (1) Staphylococcus aureus induces a reduction in granulated mast cell number in the cortical and medullary compartments of regional lymph nodes; (2) pretreatment with compound 48/80 appears to contribute to the lymphoid cell proliferation and the hypertrophic response of lymph nodes induced by S. aureus; and (3) granulated mast cells have a regulatory role on lymphoid cell proliferation.

Miconazole as inflammatory agent--I. Cellular and pathophysiological effects.

1. Subcutaneous injection of miconazole into the rat paw evoked an acute, circumscribed and long-lasting inflammation. 2. Miconazole edema presented two defined phases of rapid swelling. 3. Miconazole edema was antagonized by chlorpheniramine, dexamethasone and phenylbutazone. 4. This edema was 1.5-2 times more intense than edema due to econazole. 5. It is suggested that miconazole paw edema might be useful in the process of screening anti-inflammatory drugs.

Antiulcer action of Styrax camporum and Caesalpinia ferrea in rats. '.

Stem extracts of Styrax camporum Pohl and Caesalpinia ferrea Martius were administered orally and intraperitoneally to rats and effected a decrease in the acute ulceration number. The volume, pH, and hydrochloric acid concentration of gastric secretions were measured after administration of both extracts, atropine, and cimetidine. After oral administration there was a decrease in the gastric secretion volume without modification of the other gastric secretion parameters studied. There were modifications, however, when the extracts were administered intraperitoneally. Analgesy, influence on sleeping time, and spontaneous motor activity test results indicate a probable absence of central action components in the extracts.

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

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

Pharmacological assay of Casearia sylvestris. I: Preventive anti-ulcer activity and toxicity of the leaf crude extract.

An ethanol extract of the leaves of Brazilian Casearia sylvestris, given orally, inhibited gastric secretion in pylorus-ligated rats. At a prophylactic dose of 57.5 mg/kg, the extract showed a reduction of gastric juice more effective than misoprostol (500 micrograms/kg). In reducing hydrochloric acid output, the extract was less effective than misoprostol, cimetidine (32.0 mg/kg) and atropine (5.3 mg/kg). With the extract, the pH of the stomach contents was not significantly different from that of controls. Stress-induced lesions produced by restraint and water immersion were significantly prevented by the extract for all levels of severity when compared with the controls. The extract appeared more effective than misoprostol in suppressing light lesions, was equivalent to cimetidine and misoprostol for moderate lesions, and less effective than cimetidine and misoprostol for severe lesions. Toxicological experiments indicated a low acute toxicity, confirmed by subchronic daily testing. The oral LD50 value of greater than 1840 mg/kg was over 32 times higher than the antiulcerogenic ED50 (57.5 mg/kg).

Determination of inorganic components in Brazilian medicinal plants by neutron activation analysis.

Instrumental neutron activation analysis (INAA) has been applied to multielemental determinations of medicinal extracts obtained from the plants. Cordia Verbenacea DC, Folidago Microglossa DC, and Petiveria Alliacea. Concentrations of the elements Al, Br, Ca, Cl, Co, Cs, Fe, K, La, Mg, Mn, Na, Rb, Sb, and Zn have been determined in dried extracts of these herbs by short and long irradiations under a thermal neutron flux of 10(11)-10(13) n/cm2s in the IEA-R1 nuclear reactor. The NBS Tea Leaves (1572) and NIES Pepperbush (1) reference materials were analyzed simultaneously with the plant extracts. The results obtained in these analyses have shown a good accuracy and reproducibility of the method. The relative errors and the relative standard deviations were less than 10% for most of the elements analyzed.

Anti-inflammatory activity and sub-acute toxicity of artemetin.

The 5-hydroxy-3,6,7,3',4'-pentamethoxyflavone (artemetin) from Cordia verbenacea DC (Boraginaceae) showed marked anti-inflammatory activity using various experimental models in rats. Artemetin significantly inhibited carrageenin-induced paw edema following oral doses from 30.4 to 153.9 mg.kg-1. The doses of 102.6 and 153.9 mg.kg-1 showed an inhibitory effect similar to that of 50.0 mg.kg-1 of calcium phenylbutazone. The ED50 value of artemetin in rats was estimated to be 67.07 mg.kg-1. Repeated administration of artemetin at doses of 67.07 mg.kg-1 for a 6-day period reduced granuloma formation with a response comparable to that of 20.0 mg.kg-1 of calcium phenylbutazone. This same dose of artemetin also reduced the vascular permeability to intracutaneous histamine. Sub-acute toxicological experiments indicated a very low toxicity.