Glauce Socorro de Barros Viana

Analgesic and antiinflammatory effects of chalcones isolated from Myracrodruon urundeuva allemão.

The present work showed analgesic and antiinflammatory activities from a fraction containing three dimeric chalcones (chalcone enriched fraction - CEF), isolated from the stem-bark ethyl acetate extract of Myracrodruon urundeuva Allemao (Anacardiaceae). M. urundeuva is a popular medicinal plant used widely in Northeast Brazil, mainly as a topical female genital tract antiinflammatory. We observed that the CEF (5 and 10 mg/kg body wt., i.p. or p.o.) inhibited acetic acid-induced abdominal contractions in mice. In the formalin test, the CEF (5 and 10 mg/kg body wt.) was more effective intraperitoneally and inhibited predominantly the second phase of response. Naloxone reversed this effect, indicating an involvement of the opioid system. The CEF (10 and 20 mg/kg body wt.) also increased the reaction time to thermal stimuli in the hot-plate test in mice, after i.p. but not after p.o. administration. In the carrageenan-induced paw edema test in mice, the CEF (20 and 40 mg/kg body wt.) decreased paw volume significantly, after i.p. administration 2-4 hours after carrageenan injection. The CEF (40 mg/kg body wt.) was also active orally during the same period of time. The present work is the first report on peripheral and central analgesic effects and antiinflammatory activity of natural dimeric chalcones.

Oxidative stress in the hippocampus after pilocarpine‐induced status epilepticus in Wistar rats

The role of oxidative stress in pilocarpine‐induced status epilepticus was investigated by measuring lipid peroxidation level, nitrite content, GSH concentration, and superoxide dismutase and catalase activities in the hippocampus of Wistar rats. The control group was subcutaneously injected with 0.9% saline. The experimental group received pilocarpine (400 mg·kg−1, subcutaneous). Both groups were killed 24 h after treatment. After the induction of status epilepticus, there were significant increases (77% and 51%, respectively) in lipid peroxidation and nitrite concentration, but a 55% decrease in GSH content. Catalase activity was augmented 88%, but superoxide dismutase activity remained unaltered. These results show evidence of neuronal damage in the hippocampus due to a decrease in GSH concentration and an increase in lipid peroxidation and nitrite content. GSH and catalase activity are involved in mechanisms responsible for eliminating oxygen free radicals during the establishment of status epilepticus in the hippocampus. In contrast, no correlations between superoxide dismutase and catalase activities were observed. Our results suggest that GSH and catalase activity play an antioxidant role in the hippocampus during status epilepticus.

Antinociceptive, anti-inflammatory and bronchodilator activities of Brazilian medicinal plants containing coumarin: a comparative study

This work studied the antinociceptive, antiinflammatory and bronchodilator activities of hydroalcoholic extracts (HAEs) from Torresea cearensis, Justicia pectoralis, Eclipta alba, Pterodon polygaliflorus and Hybanthus ipecacuanha. These plants are largely used in north-eastern Brazil for respiratory tract diseases, and have in common coumarin, one of their active principles. The antinociceptive effects of all HAEs in mice were similar, and the inhibition of the acetic acid-induced writhing was 35-55% with 200 mg/kg, p.o. At this dose, the effect ranged from 41-77% with the formalin test in mice, and all the HAEs inhibited preferentially the 2nd phase of the response. In one case (P. polygaliflorus), the effect was partially reversed by naloxone. Except for the HAE from T. cearensis (200 mg/kg, p.o.) which inhibited carrageenan-induced edema by 47%, the others presented no effect orally but showed a significant activity intraperitoneally. On the other hand, T. cearensis was not active in the dextran model, while inhibitions with the other ones were lower than 30%. The bronchodilator activities of J. pectoralis and P. polygaliflorus HAEs as determined in isolated guinea-pig trachea were the most active.

The cytotoxic and embryotoxic effects of kaurenoic acid, a diterpene isolated from Copaifera langsdorffii oleo-resin.

In this work, we studied the effects of kaurenoic acid, a diterpene isolated from the oleo-resin of Copaifera langsdorffii in developing sea urchin (Lytechinus variegatus) embryos, on tumor cell growth in microculture tetrazolium (MTT) test and on mouse and human erythrocytes in hemolysis assay. Continuous exposure of embryos to kaurenoic acid starting immediately after fertilization inhibited the first cleavage (IC(50): 84.2 microM) and progressively induced embryo destruction (IC(50): 44.7 microM and < 10 microM for blastulae and larvae stages, respectively). In MTT assay, kaurenoic acid at a concentration of 78 microM produced growth inhibition of CEM leukemic cells by 95%, MCF-7 breast and HCT-8 colon cancer cells by 45% each. Further, kaurenoic acid induced a dose-dependent hemolysis of mouse and human erythrocytes with an EC(50) of 74.0 and 56.4 microM, respectively. The destruction of sea urchin embryos, the inhibition of tumor cell growth and the hemolysis of mouse and human erythrocytes indicate the potential cytotoxicity of kaurenoic acid.

Central effects of citral, myrcene and limonene, constituents of essential oil chemotypes from Lippia alba (Mill.) N.E. Brown

Citral, myrcene and limonene (100 and 200 mg/kg body wt., i.p.), constituents of essential oils from Lippia alba chemotypes, decreased not only the number of crossings but also numbers for rearing and grooming, as measured by the open-field test in mice. Although muscle relaxation detected by the rota rod test was seen only at the highest doses of citral (200 mg/kg body wt.) and myrcene (100 and 200 mg/kg body wt.), this effect was observed even at the lowest dose of limonene (50 mg/kg body wt.). Also, citral and myrcene (100 and 200 mg/kg body wt.) increased barbiturate sleeping time as compared to control. Limonene was also effective at the highest dose, and although citral did not increase the onset of sleep, it increased the duration of sleep, which is indicative of a potentiation of sleeping time. Citral (100 and 200 mg/kg body wt.) increased 2.3 and 3.5 times, respectively, the barbiturate sleeping time in mice. Similar effects were observed for myrcene and limonene at the highest dose (200 mg/kg body wt.) which increased the sleeping time around 2.6 times. In the elevated-plus maze, no effect was detected with citral up to 25 mg/kg body wt., while at a high dose it decreased by 46% the number of entries in the open arms. A smaller but significant effect was detected with limonene (5 mg/kg body wt.). While myrcene (10 mg/kg body wt.) decreased only by 22% the number of entries in the open arms, this parameter was decreased by 48% at the highest dose. Our study showed that citral, limonene and myrcene presented sedative as well as motor relaxant effects. Although only at the highest dose, they also produced a potentiation of the pentobarbital-induced sleeping time in mice, which was more intense in the presence of citral. In addition, neither of them showed an anxiolytic effect, but rather a slight anxiogenic type of effect at the higher doses.

Punica granatum (pomegranate) extract is active against dental plaque.

In the present work, we studied the effect of the hydro-alcoholic extract (HAE) from Punica granatum (pomegranate) fruits on dental plaque microorganisms. The study was conducted on 60 healthy patients (33 females and 27 males, with age ranging from 9 to 25 years) using fixed orthodontic appliances, and randomly distributed into 3 groups of 20 patients each. The first group (control) used distilled water, while the second and third groups used chlorhexidine (standard) and HAE as mouth-rinses, respectively. The dental plaque material was collected from each patient, before and after a 1-min mouth-rinse with 15 ml of either distilled water, chlorhexidine or HAE. In both dental plaque collections, the material was removed from patients without oral hygiene, for 24 h (no tooth brushing). Dental plaque samples were diluted in phosphate buffered saline (PBS) plated on Mueller-Hinton agar, and incubated for 48 h, at 37°C. Results, expressed as the number of colony forming units per milliliter (CFU/mL), show that the HAE was very effective against dental plaque microorganisms, decreasing the CFU/ml by 84% (CFU X105, before mouth-rinse: 154.0 ±41.18; after mouth-rinse: 25.4 ±7.76). While similar values were observed with chlorhexidine, used as standard and positive control (79% inhibition), only an 11% inhibition of CFU/ml was demonstrated in the distilled water group, negative control (CFUX 105, before mouth-rinse: chlorhexidine, 208.7 ±58.81and distilled water, 81.1 ±10.12; after mouth-rinse: chlorhexidine, 44.0 ±15.85 and distilled water, 71.9 ±8.68). The HAE presented also an antibacterial activity against selected microorganisms, and may be a possible alternative for the treatment of dental plaque bacteria.

Antinociceptive effect of the essential oil from Cymbopogon citratus in mice

The essential oil (EO) from leaves of Cymbopogon citratus increased the reaction time to thermal stimuli both after oral (25 mg/kg) and intraperitoneal (25-100 mg/kg) administration. EO (50-200 mg/kg, p.o. or i.p.) strongly inhibited the acetic acid-induced writhings in mice. In the formalin test, EO (50 and 200 mg/kg, i.p.) inhibited preferentially the second phase of the response, causing inhibitions of 100 and 48% at 200 mg/kg, i.p. and 100 mg/kg, p.o., respectively. On the other hand, the opioid antagonist naloxone blocked the central antinociceptive effect of EO, suggesting that EO acts both at peripheral and central levels.

Anxiolytic-like effect of Carvacrol (5-isopropyl-2-methylphenol) in mice: involvement with GABAergic transmission.

Carvacrol (5‐isopropyl‐2‐methylphenol) is a monoterpenic phenol present in the essencial oil of many plants. It is the major component of the essential oil fraction of oregano and thyme. This work presents the behavioral effects of carvacrol in animal models of elevated plus maze (EPM), open field, Rotarod and barbiturate‐induced sleeping time tests in mice. Carvacrol (CVC) was administered orally, in male mice, at single doses of 12.5; 25 and 50 mg/kg while diazepam 1 or 2 mg/kg was used as standard drug and flumazenil (2.5 mg/kg) was used to elucidate the possible anxiolytic mechanism of CVC on the plus maze test. The results showed that CVC, at three doses, had no effect on the spontaneous motor activity in the Rotarod test nor in the number of squares crossed in the open‐field test. However, CVC decreased the number of groomings in the open‐field test. In the plus maze test, CVC, at three doses significantly increased all the observed parameters in the EPM test and flumazenil was able to reverse the effects of diazepam and CVC. Therefore, CVC did not alter the sleep latency and sleeping time in the barbiturate‐induced sleeping time test. These results show that CVC presents anxiolytic effects in the plus maze test which are not influenced by the locomotor activity in the open‐field test.

Pilocarpine-induced status epilepticus in rats: lipid peroxidation level, nitrite formation, GABAergic and glutamatergic receptor alterations in the hippocampus, striatum and frontal cortex.

The aim of the study was to investigate the lipid peroxidation levels, nitrite formation, GABAergic and glutamatergic receptor densities in the hippocampus, frontal cortex and striatum of Wistar rats after seizures and status epilepticus (SE) induced by pilocarpine. The control group was treated with 0.9% saline and sacrificed 1 h after the treatment. One group of rats was administered with pilocarpine (400 mg/kg sc) and sacrificed 1 h after treatment. The result shows that pilocarpine administration and the resulting SE produced a significant increase of lipid peroxidation level in the hippocampus (46%), striatum (25%) and frontal cortex (21%). In nitrite formation, increases of 49%, 49% and 75% in hippocampus, striatum and frontal cortex, respectively, was observed. Pilocarpine treatment induced down-regulation of GABAergic receptors in the hippocampus (38%), striatum (15%) and frontal cortex (11%). However, with regard to glutamatergic receptor densities, increases in the hippocampus (11%), striatum (17%) and frontal cortex (14%) was observed during the observation period. These results show a direct evidence of lipid peroxidation and nitrite formation during seizure activity that could be responsible for the GABAergic and glutamatergic receptor concentration changes during the establishment of SE induced by pilocarpine.

Effects of lithium, alone or associated with pilocarpine, on muscarinic and dopaminergic receptors and on phosphoinositide metabolism in rat hippocampus and striatum.

The mechanism of action of lithium (Li) alone or with pilocarpine (Pilo), focusing on muscarinic and dopaminergic systems and also on phosphoinositide metabolism was studied. Li (3 mEq/kg) administered to rats once (1 d) or daily for 7 days (7 d), 24 h before Pilo (15 mg/kg), exacerbated cholinergic signs, leading to tremors. convulsions and brain lesions. Increases in muscarinic receptors (MR) of 29 and 49% were observed in the hippocampus after atropine (Atro) and Li-Atro-Pilo treatments, respectively, as compared to controls (Atro) and the Li-Pilo group (Li-Atro-Pilo). In the striatum, except for the 37% increase in the Li-Atro (50 mg/kg)-Pilo group as compared to the Li-Pilo one, no other changes were observed in MR. A decrease of 32% on average in D2-like receptors (D2R) was detected in the hippocampus in the group Li-7d. On the contrary, in the striatum an increase (25%) in the Li-7d group was observed and this effect was blocked by Li-Pilo. As far as inositol phosphates (IP) and phosphatidylinositol-4,5-biphosphate (PIP2) metabolism is concerned, Li caused a decrease (28%) and an increase (60%) in IP and PIP2 accumulations, respectively, in hippocampus slices while Pilo only altered IP accumulation (32% decrease). In this area the association of Li-Atro (10 mg/kg)-Pilo also caused a decrease (36%) in PIP2 as compared to the Li-Pilo group. In striatal slices, except for the Li, Atro (10 mg/kg) and Li-Atro (10 mg/kg)-Pilo groups which showed a decrease (33 40%) in IP accumulation, no other alteration was detected. The potentiation of the effect of Pilo by Li does not seem to depend on the PI metabolism, but instead on its involvement with muscarinic and dopaminergic systems.