Roseli Soncini

Prostaglandins mediate depressive-like behaviour induced by endotoxin in mice

Sickness behaviour appears to be the expression of a central motivational state that reorganises the organisms priorities to cope with infectious pathogens. To evaluate the possible participation of prostaglandins in lipopolysaccharide-induced sickness behaviours, mice were submitted to the tail suspension test (TST), forced swim test (FST), open field test and dark-light box test. Lipopolysaccharide (LPS, 100microg/kg; i.p.) administration increased the time spent immobile in the TST, increased the time spent floating in the FST, and depressed locomotor activity in the open field. Indeed, treatment with LPS decreased the total number of transitions made between the dark and light compartments of the apparatus. Pretreatment with indomethacin (10mg/kg; i.p.) or nimesulide (5mg/kg) blocked behavioural changes induced by LPS in the FTS, TST, open field and light-dark box test. This effect was similar to pretreatment with dexamethasone (1mg/kg), which is a steroidal drug that inhibits immune and inflammatory responses, including cytokine production. These findings confirm previous observations that have reported LPS-induced sickness behaviours. In addition, they provide evidence that the synthesis of prostaglandins is necessary for changes in depressive-like and exploratory behaviours in mice, which is supported by the fact that COX inhibitors also attenuate LPS-induced behavioural changes.

Antinociceptive effect of extract of Emilia sonchifolia in mice.

AIM OF THE STUDY Emilia sonchifolia (L.) DC. (Asteraceae) is a medicinal plant traditionally used in Brazilian folk medicine to treat asthma, fever, cuts, wounds and rheumatism. This study was conducted to establish the antinociceptive properties of hydroethanolic extract from aerial parts of Emilia sonchifolia in mice using chemical and thermal models of nociception. MATERIALS AND METHODS To evaluate the antinociceptive effect of Emilia sonchifolia hydroethanolic extract (EsHE) administered by oral route, peripheral (acetic acid-induced abdominal writhing and formalin), spinal (tail flick) and supra-spinal (hot plate) behavioral models of acute pain were used. High-performance liquid chromatography (HPLC) was used to determine the fingerprint chromatogram of the EsHE. RESULTS The EsHE at test doses of 100 and 300 mg/kg, p.o. clearly demonstrated antinociceptive activity in all tests. The extract had a stronger antinociceptive effect than morphine. Administration of the opioid receptor antagonist, naloxone, completely inhibited the antinociceptive effect induced by EsHE (100mg/kg). The presence of phenolic compounds in the extract of Emilia sonchifolia was confirmed using HPLC. CONCLUSION The extract of Emilia sonchifolia markedly exhibits opioid-mediated anti-nociceptive activity action in mice. Thus, may be useful in the treatment of inflammatory hyperalgesic disorders, which supports previous claims of its traditional use.

Anti-inflammatory and antipyretic effects of Sonchus oleraceus in rats.

ETHNOPHARMACOLOGICAL RELEVANCE Sonchus oleraceus L. has been used to relieve headaches, general pain, hepatitis, infections, inflammation and rheumatism in Brazilian folk medicine. Nevertheless, scientific information regarding this species is scarce; there are no reports related to its possible anti-inflammatory effects. AIM OF THE STUDY This study was aimed at evaluating the scientific basis for the traditional use of Sonchus oleraceus using in vivo inflammatory models. MATERIALS AND METHODS Carrageenan-induced paw edema, peritonitis and febrile response induced by lipopolysaccharide tests, as well as fibrovascular tissue growth induced by s.c. cotton pellet implantation were used to investigate the anti-inflammatory activity of Sonchus oleraceus hydroethanolic extract (SoHE) in rats. RESULTS The SoHE at test doses of 100-300 mg/kg p.o. clearly demonstrated anti-inflammatory effects by reduced paw edema induced by carragenan, inhibited leukocyte recruitment into the peritoneal cavity and reduced LPS-induced febrile response, and in the model of chronic inflammation using the cotton pellet-induced fibrovascular tissue growth in rats, the SoHE significantly inhibited the formation of granulomatous tissue. The extract administered at 300 mg/kg p.o. had a stronger anti-inflammatory effect than indomethacin (10mg/kg) or dexamethasone (1mg/kg). CONCLUSION The hydroethanolic extract of Sonchus oleraceus markedly demonstrated anti-inflammatory action in rats, which supports previous claims of its traditional use.

Antiinflammatory properties of Morus nigra leaves

The aim of the present study was to investigate antiinflammatory activity of the methylene chloride extract of Morus nigra in animal models. Carrageenan‐induced paw edema as well as fibrovascular tissue growth induced by s.c. cotton pellet implantation were used to investigate the antiinflammatory activity of Morus nigra extract (MnE) in rats. A HPLC fingerprint was used for phytochemical analysis of the extracts. The MnE at test doses of 100–300 mg/kg p.o. clearly demonstrated antiinflammatory effects by reduced paw edema induced by carragenan and significantly inhibited the formation of granulomatous tissue. In addition, chemical compounds isolated from Morus nigra, including betulinic acid, β‐sitosterol and germanicol, may be responsible for the antiinflammatory effect of the extract. Copyright

Anxiolytic-like effect of Sonchus oleraceus L. in mice

ETHNOPHARMACOLOGICAL RELEVANCE Sonchus oleraceus L. has been used as a general tonic in Brazilian folk medicine. Nevertheless, available scientific information regarding this species is scarce; there are no reports related to its possible effect on the central nervous system. AIM OF THE STUDY This study was conducted to establish the anxiolytic effect of extracts from the aerial parts of Sonchus oleraceus. MATERIALS AND METHODS This study evaluated the effect of hydroethanolic and dichloromethane extracts of Sonchus oleraceus in mice submitted to the elevated plus-maze and open-field tests. Clonazepam was used as the standard drug. RESULTS In the elevated plus-maze test, the Sonchus oleraceus extracts increased the percentage of open arm entries (P<0.05) and time spent in the open-arm portions of the maze (P<0.05). The extracts induce an anti-thigmotactic effect, evidenced by increased locomotor activity into the central part of the open field set-up (P<0.05). The extracts administered at 30-300 mg/kg, p.o. had a similar anxiolytic effect to clonazepam (0.5 mg/kg, p.o.). CONCLUSION These data indicate that Sonchus oleraceus extract exerts an anxiolytic-like effect on mice.

Hypotensive effect of aqueous extract of Averrhoa carambola L. (Oxalidaceae) in rats: An in vivo and in vitro approach

AIM OF THE STUDY Averrhoa carambola L. (Oxalidaceae) leaves are used in Brazilian traditional medicine to treat hypertension. This study was conducted to evaluate the hypotensive effect of the aqueous extract of Averrhoa carambola (AEAc) and its underlying mechanisms in the isolated rat aorta. MATERIALS AND METHODS The effect of AEAc on the mean arterial pressure (MAP) was determined in vivo in anesthetized rats. In vitro, thoracic aortic rings were isolated and suspended in organ baths, and the effects of AEAc were studied by means of isometric tension recording experiments. In HPLC analysis, the fingerprint chromatogram of AEAc was established. RESULTS In normotensive rats, AEAc (12.5-50.0 mg/kg, i.v.) induced dose-dependent hypotension. In vitro, AEAc caused a depression in the E(max) response to phenylephrine without a change in sensibility. Also, in a depolarized Ca(2+)-free medium, AEAc inhibited CaCl(2)-induced contractions and caused a concentration-dependent rightward shift of the response curves, indicating that AEAc inhibited the contractile mechanisms involving extracellular Ca(2+) influx. CONCLUSIONS These results demonstrate the hypotensive effects of AEAc, and these effects may, in part, be due to the inhibition of Ca(2+), which supports previous claims of its traditional use.

Inhibition of nitric oxide synthase accentuates endotoxin-induced sickness behavior in mice

Sickness behavior appears to be the expression of a central motivational state that reorganizes an organisms priorities to cope with infectious pathogens. To evaluate the possible participation of nitric oxide (NO) in lipopolysaccharide-induced sickness behaviors, mice were submitted to the forced swim test (FST), open field test and dark-light box test. Food intake and corticosterone plasma levels were evaluated. Lipopolysaccharide (LPS, 100 μg/kg; i.p.) administration increased the time spent floating in the FST and decreased locomotor activity in the open field. Indeed, treatment with LPS decreased the total number of transitions between the dark and light compartments of the apparatus. In addition, LPS reduced food intake and increased corticosterone levels. Pretreatment with L-NAME (30 mg/kg; i.p.) or aminoguanidine (50mg/kg; i.p.) accentuated the behavioral changes induced by LPS in the FST, open field and light-dark box tests as well as induced an increment in hypophagia and in corticosterone levels. These findings confirm previous observations that have reported LPS-induced sickness behaviors. In addition, they provide evidence that the synthesis of NO modulates changes in depressive-like and exploratory behaviors in mice, which is supported by the fact that NO synthase inhibitors also attenuate LPS-induced behavioral changes. In addition, the present study suggests that NO may have a protective role, acting in an inhibitory feedback manner to limit LPS-induced sickness behavior.

Dipyrone attenuates acute sickness response to lipopolysaccharide in mice

Sickness behavior appears to be the expression of a central motivational state that reorganizes the organisms priorities to cope with infectious pathogens. To evaluate the effect of dipyrone in lipopolysaccharide (LPS)-induced sickness behavior, mice were subjected to the forced swim test (FST), tail suspension test (TST), dark-light box test, open field test, sucrose preference intake test and food intake test. LPS administration increased the immobility time in the TST, increased the time spent floating in the FST, and depressed locomotor activity in the open field test. Treatment with LPS decreased the total number of transitions made between the dark and light compartments of the apparatus and induced anhedonia and anorexia. Pre-treatment with dipyrone (10, 50, or 200 mg/kg) attenuated behavioral changes induced by LPS in the FST, TST, open field and light-dark box tests. In addition, dipyrone prevented anhedonia and anorexia in mice challenged with LPS. Considering that dipyrone attenuates LPS-induced behavioral changes, it is proposed that LPS-induced sickness behavior is dependent on the COX pathway.

Anti-inflammatory activities of enzymatic (alcalase) hydrolysate of a whey protein concentrate

This study was designed to evaluate the anti-inflammatory effects of whey protein hydrolysate (WPH) in mice. Hydrolysis for this experiment was conducted in a pH-stat at 20% degree of hydrolysis. Carrageenan-induced paw edema, peritonitis induced by lipopolysaccharide (LPS) and acetic acid-induced writhing were tested to investigate anti-inflammatory activity. Overall, WPH inhibited carrageenan-induced mice paw edema significantly with doses of 30 mg/kg (p < 0.001), 100 mg/kg (p < 0.01) and 300 mg/kg (p < 0.001) at 3 h post carrageenan. The inhibitory values of edema were 60.34, 39.65 and 68.96%, respectively. After 4 h and an intraperitoneal injection of LPS (100 μg/kg), WPH further inhibited leukocyte recruitment to the peritoneal cavity of mice at a dose of 300 mg/kg (p < 0.05). In a number of the writhing episodes, WPH reduced contortions using a dose of 300 mg/kg. These results indicate that the hydrolysate obtained by treatment with alcalase demonstrated anti-inflammatory activity in the experimental models. All the anti-inflammatory actions obtained were also suggested to be due the presence of glutamine. Key words : Whey protein, proteases, hydrolysate, anti-inflammatory activity, mice.

Inhibition of endogenous glucocorticoid synthesis aggravates lung injury triggered by septic shock in rats.

The aim of this study was to determine the effects of previous administration of metyrapone (met) on the acute lung injury (ALI) induced by caecal ligation and puncture (CLP) and to explore mets relationship with endogenous glucocorticoids (GCs) as measured by inflammatory, oxidative and functional parameters. One hundred and thirty‐five Wistar rats were divided into three main groups: Control (Naïve), Sham and CLP. The animals received pretreatment one hour before surgery. The Naïve group did not undergo any procedure or pretreatment. The Sham group only had the caecum exposed and was pretreated with saline. The CLP group was divided into three pretreatments: metyrapone (CLP met 50 mg/kg i.p.), dexamethasone (CLP dex 0.5 mg/kg i.p.) or saline (CLP sal equivalent volume of 0.9% NaCl). Analyses were performed after 6 and 24 h of sepsis. Previous administration of met significantly increased inflammatory cells, as well as myeloperoxidase (MPO) activity in the lung tissue and alveolar collapsed area, with consequent impairment of respiratory mechanics being observed compared to Sham and Naïve; CLP sal exhibited similar results to those of met. The met reduced corticosterone (CCT) levels and dramatically increased hydrogen peroxide (H2O2) levels in the lung tissue compared to CLP sal. Our results suggest that previous administration of met may have contributed to increased pulmonary oxidative stress and increased mortality by mechanisms dependent of endogenous GC.