Márcia Maria de Souza

Mechanisms for memory types differ

The formation of long-term memory takes several hours, during which time memories rely on short-term systems,,,. For over 100 years, the main unanswered question of memory research has been whether short-term memory is a necessary step towards long-term memory,, or whether they are separate processes,. Here we report four treatments that block short-term memory while leaving long-term memory intact, showing that these memory systems are separate to some degree.

Melanin-concentrating hormone (MCH) modifies memory retention in rats.

The purpose of the present study was to evaluate the possible effect of melanin-concentrating hormone (MCH) on learning and memory by using the one-trial step-down inhibitory avoidance test in rats. The peptide was infused into hippocampus, amygdala, and entorhinal cortex. MCH caused retrograde facilitation when given at 0 or 4 h post-training into hippocampus, but only at 0 h into amygdala. From these results, it seems that MCH modulates memory early after training by acting on both the amygdala and hippocampus and, 4 h after training, on the hippocampus.

Anxiolytic-, antidepressant- and anticonvulsant-like effects of the alkaloid montanine isolated from Hippeastrum vittatum

Compounds isolated from different members of the Amaryllidaceae family are becoming relevant options for the treatment of neurological disorders and neurodegenerative diseases. In particular, species of the Hippeastrum genus are important source of alkaloids with a wide profile of putative therapeutical applications. Here, we report on the behavioral and pharmaco-toxicological characterization of montanine, an isoquinoline alkaloid isolated from Hippeastrum vittatum, an ornamental plant found throughout the world. In mice, montanine showed a LD(50) of 64.7 mg/kg and 67.6 mg/kg for male and female, respectively. When given i.p., montanine dose-dependently decreased sodium pentobarbital-induced sleep, protected against pentylenetetrazole-provoked convulsions, increased the number of entries and the time spent in the open arms of an elevated plus maze and augmented the time spent struggling during a forced swimming test. When given immediately after inhibitory avoidance training, montanine did not affect avoidance memory retention in rats. Our results suggest that montanine, as other alkaloids isolated from Amaryllidaceae species, has psychopharmacological activities including anxiolytic, antidepressive and anticonvulsive effects.

Preliminary studies on the antinociceptive activity of Vaccinium ashei berry in experimental animal models.

The aim of this study was to carry out pharmacological screening in order to evaluate the potential effects of lyophilized fruits of different cultivars of Vaccinium ashei Reade (Family Ericaceae) berries, commonly known as rabbiteye blueberries, on nociception. This was achieved using the formalin, hot plate, tail-flick, and writhing tests in mice. During this experiment the mice consumed approximately 3.2-6.4 mg/kg/day (p.o.) of the anthocyanins. The extract was administered for 21 days or 60 minutes before test. Morphine and diclofenac (10 mg/kg, p.o.) as the standard drug (positive control) and water (via oral gavage) as the negative control were administered before all tests. The blueberry extract produced a significant decrease in constrictions induced by acetic acid and caused graded inhibition of the second phase of formalin-induced pain. Moreover, in both the hot plate and tail-flick tests, it significantly increased the threshold. These data suggest that the extract from V. ashei produced antinociceptive effects, as demonstrated in the experimental models of nociception in mice. Additional experiments are necessary in order to clarify the true target for the antinociceptive effects of rabbiteye blueberry extract.

Topical curcumin-loaded hydrogels obtained using galactomannan from Schizolobium parahybae and xanthan.

The curcumin (CUR)-loaded binary hydrogel was formulated using xanthan and galactomannan from Schizolobium parahybae (guapuruvu). The binary hydrogels presented gel characteristics, stable pH values and mechanical stress resistance even after 45 days of heat exposure (45 °C). The CUR-loaded hydrogel content was 98.6% for XGMC (xanthan and galactomannan with CUR-microemulsion) after the stability test. The in vitro cytotoxicity analysis suggested non-cutaneous membrane irritation, and the in vitro skin permeation analysis indicated 2.15 to 2.50 μg mL(-1) CUR at the stratum corneum, epidermal and dermal levels. The XGEC (xanthan and galactomannan with CUR solubilized in ethanol) and XGMC hydrogels presented 76.8 and 63.2% inhibition of topical inflammation, respectively. Chemical stability and non-cytotoxicity analysis confirm the safety of prolonged exposure of the skin during the topical treatment, offering long-lasting XGEC and XGMC action.

Antidepressant-like effect of quercetin in bulbectomized mice and involvement of the antioxidant defenses, and the glutamatergic and oxidonitrergic pathways

Olfactory bulbectomy (OB) is an animal model of depression that can mimic symptoms that are characteristic of depressive patients, such as behavioral, neurochemical and neuromorphological changes. Quercetin decreased the immobility time in the forced swimming test and tail suspension test. With the open field test, quercetin did not alter the locomotor activity of mice and in the splash test, quercetin increased the time spent grooming. The repeated treatment with quercetin (25mg/kg, for 14days) reversed the behavioral hyperactivity induced by OB in the open field test and was able to prevent depressant-like effects in the forced swimming test and tail suspension test. Regarding oxidative stress, OB reduced the levels of glutathione and increase the activity of superoxide dismutase and lipid hydroperoxide content (LOOH) in the hippocampus. Only the increase in LOOH levels was reversed by treatment with quercetin. In a further series of experiments with non-bulbectomized mice, the antidepressant effect of quercetin in the tail suspension test was reversed by the pretreatment of mice with NMDA, l-arginine or sildenafil. The administration of methylene blue and 7-nitroindazole, in combination with an underactive dose of quercetin (5mg/kg, p.o.), decreased the immobility time in the tail suspension test compared with the use of drug alone. There was no significant change in locomotor activity in the open field test. Our results suggest that the antidepressant effect of quercetin is dependent on the inhibition of the NMDA receptors and/or synthesis of nitric oxide. In addition, considering the reduction of LOOH levels on the hippocampus, we verify that the antioxidant effects of quercetin also contribute to its antidepressive potential. These data contribute to the understanding of the mechanisms involved in the antidepressant effect of quercetin and reinforce the involvement of the NMDA receptors and the nitric oxide on the pathophysiology of depression.

Chemical composition, antioxidant and antinociceptive properties of Litchi chinensis leaves

Litchi chinensis has been traditionally used in folk medicine to treat several ailments. In this study, we investigated the chemical composition, antioxidant and antinociceptive activity of L. chinensis leaves.

Aleurites moluccana and its main active ingredient, the flavonoid 2″-O-rhamnosylswertisin, have promising antinociceptive effects in experimental models of hypersensitivity in mice

This study investigated the antinociceptive effect of Aleurites moluccana dried extract (DE; 125 to 500 mg/kg, p.o.) and the isolated flavonoid 2″-O-rhamnosylswertisin (5 to 50.6 μmol/kg, p.o.) using different models of long-lasting inflammatory and neuropathic pain in mice. Attempts were made to analyse the mechanisms through which A. moluccana exerted its effects. A. moluccana DE inhibited complete Freunds adjuvant (CFA)-induced mechanical nociception. It was also evidenced by a reduction of sensitization in the contralateral hindpaw. The extract reversed the mechanical hypersensitivity of partial ligation of sciatic nerve (PLSN)-treated animals, similar to gabapentin. In PLSN model, the opioid, dopaminergic and oxidonitrergic pathways were involved in the A. moluccana DE antinociceptive effects. A single dose of 2″-O-rhamnosylswertisin inhibited the carrageenan- and CFA-induced mechanical nociception. Furthermore, the compound caused expressive antinociception in PLSN-mice, with inhibition value greater than obtained with gabapentin. Oral treatment with the extract or the isolated compound attenuated the neutrophil migration and IL-1β levels following carrageenan injection. Of note, A. moluccana DE did not interfere with thermal sensitivity in healthy mice. The absence of side effects, including interference in locomotor activity, motor performance in animals treated with the extract, showed excellent potential for the therapeutic use of this medicinal plant in treating persistent pain in humans.

Development of hydroethanolic extract of Ipomoea pes-caprae using factorial design followed by antinociceptive and antiinfl ammatory evaluation

Ipomoea pes-caprae (L.) R. Br., Convolvulaceae, is a medicinal plant that grows abundantly as a pan-tropical stand plant. The 32 (two factors and three levels) factorial design, was applied to determine the best time and drug/solvent proportion to maximize the flavonoid content in the hydroethanolic extract by maceration process. The antinociceptive and anti-inflammatory effects were studied at 5-20 mg/kg, i.p., using the writhing test and carrageenan-induced pleurisy models in mice. The optimized extract was able to inhibit more than 50% of abdominal writhing at 20 mg/kg, with 55.88%±2.4 of maximum inhibition. Indomethacin, used as positive control, inhibited 64.86% at 10 mg/kg. In the pleurisy model, the extract produced dose-dependent inhibition of the first phase of inflammation (4 h) in the pleural cavity induced by injection of carrageenan (1%) in mice. It inhibited 50%±0.82 (p<0.01) of exudation induced by carrageenan, and 60.88%±0.14 (p<0.01) of leukocyte migration to the pleural cavity. In conclusion, the results validate the technological conditions of the maceration process to produce an optimized bioactive herb extract for the development of analgesic and anti-inflammatory phytopharmaceuticals using 70 oGL ethanol, a plant to solvent ratio of 12.5% (w/v), and ten days of maceration.

Antihyperalgesic effects of myrsinoic acid B in pain-like behavior induced by inflammatory and neuropathic pain models in mice.

BACKGROUND:Myrsinoic Acid B (MAB) is a diprenylated benzoic acid widely found in the vegetal kingdom. Recent studies demonstrate that MAB has important antinociceptive effects in models of chemically or thermally induced nociception in mice. METHODS:In the present study we evaluated the effect of MAB in different models of inflammatory and neuropathic hypersensitivity in mice. RESULTS:This study demonstrates that the pretreatment with MAB, given orally (8.4 to 83.8 &mgr;mol/kg), inhibited carrageenan- and complete Freund adjuvant-induced mechanical hypersensitivity. When administered after the induction of hypersensitivity, MAB also reduced the mechanical hypersensitivity in the ipsilateral and in the contralateral hindpaws of mice injected with complete Freund adjuvant, interfering with a signaling cascade already established. MAB reversed the hypersensitivity (mechanical and thermal) of operated animals, with similar results to those observed with gabapentin. MAB activity was evident when administered either systemically (PO or IV) or intrathecally, suggesting interference in the central pathways of pain control. Furthermore, MAB seems to present an antiinflammatory effect evidenced by the interference in both the neutrophil migration and in the increase of interleukin-1&bgr; levels after carrageenan injection. Of note, MAB treatment did not interfere with mechanical or thermal sensitivity in healthy mice, a frequent characteristic of commonly used analgesics, such as morphine or gabapentin. Side effects including interference in locomotor activity, motor performance, and body temperature in animals treated with MAB were absent. CONCLUSIONS:MAB reduced mechanical and thermal hypersensitivity in mice submitted to models of inflammatory and neuropathic pain, showing excellent potential for treating persistent pain in humans.