Antidepressant-like effects of fractions, essential oil, carnosol and betulinic acid isolated from Rosmarinus officinalis L.

The aim of this study was to investigate the antidepressant-like effect of fractions from Rosmarinus officinalis L.: ethyl acetate 1 and 2 (AcOEt1 and 2), hexane (HEX), ethanolic (ET), and essential oil-free (EOF) fractions, as well as essential oil, the isolated compounds carnosol and betulinic acid in the tail suspension test, a predictive test of antidepressant activity. Swiss mice were acutely administered by oral route (p.o.) with fractions, essential oil or isolated compounds, 60 min before the tail suspension test or open-field test. All of them produced a significant antidepressant-like effect: AcOEt1, ET, EOF fractions and essential oil (0.1-100mg/kg, p.o); HEX (0.1-10mg/kg, p.o) and AcOEt2 fraction (0.1-1mg/kg, p.o), carnosol (0.01-0.1mg/kg, p.o.) isolated from the HEX fraction and betulinic acid (10mg/kg, p.o.), isolated from the AcOEt1 and AcOEt2 fractions. No psychostimulant effect was shown in the open-field test, indicating that the effects in the tail suspension test are specific. This study suggests that carnosol and betulinic acid could be responsible for the anti-immobility effect of extracts from R. officinalis.

A comparison between ozonolysis and sonolysis/ozonolysis treatments for the degradation of the cytostatic drugs methotrexate and doxorubicin: Kinetic and efficiency approaches.

Cytostatics are a major class of chemotherapy drugs with great potential to cause genotoxic and/or mutagenic effects in all organisms. Currently, hospital wastewater treatment systems (HWTS) are not able to remove these compounds and they are discharged to the environment. Thus, the objective of this study was to investigate the oxidative degradation of the cytostatic drugs doxorubicin (DOXO) [(8s,10s)-10-(4-amino-5-hydroxy-6-methyl-tetrahydro-2h-pyran-2-yloxy)-6,8,11-trihydroxy-8-(2-hydroxyacetyl)-1-methoxy-7,8,9,10-tetrahydrotetracene-5,12-dione] and methotrexate (METHO) {N-[4-[[(2,4-diamino-6-pteridinyl)methyl]methylamino]benzoyl]-L-glutamic acid} by ozonolysis alone and using a combined sonolysis/ozonolysis process on bench-scale at different pH values. Besides determining the degradation efficiency, a kinetic approach was applied to determine the reaction order and rate constants for different oxidative processes carried out at pH 7.0, which is the normal pH of hospital wastewater. The results showed that the removal efficiency of these compounds is pH-dependent. A combination of sonolysis and ozonolysis processes is more efficient than the ozonolysis process alone for the degradation of doxorubicin at all pH values, while methotrexate can easily be degraded by ozonolysis alone or sonolysis/ozonolysis methodologies at any pH.

Rosmarinus officinalis L. hydroalcoholic extract, similar to fluoxetine, reverses depressive-like behavior without altering learning deficit in olfactory bulbectomized mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Rosemary, Rosmarinus officinalis L., has several therapeutic applications in folk medicine for the treatment of a wide range of diseases, including depression. AIM OF THE STUDY: To evaluate the ability of Rosmarinus officinalis hydroalcoholic extract (ROHE), as compared to the positive control fluoxetine, to reverse behavioral (hyperactivity, anhedonic behavior and learning deficit in water maze) and biochemical alterations (serum glucose level and acetylcholinesterase, AChE, activity) induced by an animal model of depression, the olfactory bulbectomy (OB) in mice. MATERIALS AND METHODS: Locomotor and exploratory behavior was assessed in the open-field, novel object and novel cage tests, anhedonic behavior was assessed in the splash test; cognitive deficits were evaluated in the water maze task. For the first set of experiments, ROHE (10-300 mg/kg) or fluoxetine (10mg/kg) was administered once daily (p.o.) for 14 days after OB and the behavioral tests were performed. For the second set of experiments, serum glucose and hippocampal and cerebrocortical AChE activity were determined in OB and SHAM-operated mice treated orally with ROHE (10mg/kg), fluoxetine (10mg/kg) or vehicle. RESULTS: ROHE (10-300 mg/kg), similar to fluoxetine, reversed OB-induced hyperactivity, increased exploratory and anhedonic behavior. OB needed significantly more trials in the training session to acquire the spatial information, but they displayed a similar profile to that of SHAM mice in the test session (24h later), demonstrating a selective deficit in spatial learning, which was not reversed by ROHE or fluoxetine. A reduced serum glucose level and an increased hippocampal AChE activity were observed in bulbectomized mice; only the latter effect was reversed by fluoxetine, while both effects were reversed by ROHE. CONCLUSIONS: ROHE exerted an antidepressant-like effect in bulbectomized mice and was able to abolish AchE alterations and hypoglycemia, but not spatial learning deficit induced by OB. Overall, results suggest the potential of Rosmarinus officinalis for the treatment of depression, validating the traditional use of this plant.

Antidepressant-like effect of the extract of Rosmarinus officinalis in mice: involvement of the monoaminergic system.

Rosemary, Rosmarinus officinalis L. (Labiatae) has several therapeutic applications in folk medicine in curing or managing a wide range of diseases, including depression. In this study, the effect of the hydroalcoholic extract of the stems and leaves of this plant was investigated in two behavioral models, the forced swimming test (FST) and tail suspension test (TST) in mice. The extract of R. officinalis produced an antidepressant-like effect, since the acute treatment of mice with the extract by p.o. route significantly reduced the immobility time in the FST (100 mg/kg) and TST (10-100 mg/kg), as compared to a control group, without accompanying changes in ambulation in the open-field test. Moreover, the repeated administration (14 days) of the hydroalcoholic extract of R. officinalis by p.o. route also produced an antidepressant-like effect in the TST (100-300 mg/kg). The pretreatment of mice with p-chlorophenylalanine (PCPA, 100 mg/kg, i.p., an inhibitor of serotonin synthesis, for 4 consecutive days), NAN-190 (0.5 mg/kg, i.p., a 5-HT(1A) receptor antagonist), ketanserin (5 mg/kg, i.p., a 5-HT(2A) receptor antagonist), 1-(m-chlorophenyl) biguanide (mCPBG, 10 mg/kg, i.p., a 5-HT(3) receptor agonist), prazosin (1 mg/kg, i.p., an alpha(1-)adrenoceptor antagonist), SCH23390 (0.05 mg/kg, s.c., a dopamine D(1) receptor antagonist) or sulpiride (50 mg/kg, i.p., a dopamine D(2) receptor antagonist), but not yohimbine (1 mg/kg, i.p., an alpha(2-)adrenoceptor antagonist) was able to reverse the anti-immobility effect of the extract (10 mg/kg, p.o.) in the TST. The combination of MDL72222, (0.1 mg/kg, i.p., a 5-HT(3) receptor antagonist) with a sub-effective dose of the extract of R. officinalis (1 mg/kg, p.o.) produced an anti-immobility effect in the TST. The results suggest that the antidepressant action of the extract of R. officinalis is mediated by an interaction with the monoaminergic system and that this plant should be further investigated as an alternative therapeutic approach for the treatment of depression.

Chemical composition and antibacterial activity of essential oils of Eugenia species.

The essential oils of the leaves of Eugenia brasiliensis, Eugenia beaurepaireana, and Eugenia umbelliflora were analyzed by GC-MS. The major compounds found in the oil of E. brasiliensis were spathulenol (12.6%) and tau-cadinol (8.7%), of E. beaurepaireana were beta-caryophyllene (8.0%) and bicyclogermacrene (7.2%), and of E. umbelliflora were viridiflorol (17.7%) and beta-pinene (13.2%). These oils were assayed to determine their antibacterial activity against Staphylococcus aureus, Pseudomonas aeruginosa, and Escherichia coli. All of the oils analyzed showed antibacterial activity, ranging from moderate to strong, which was most accentuated for the E. umbelliflora and E. brasiliensis oils, which strongly inhibited the growth of S. aureus giving values of MIC = 119.2 and 156.2 microg/mL, respectively.

Synergistic neurotoxicity induced by methylmercury and quercetin in mice.

Methylmercury (MeHg) is a highly neurotoxic pollutant, whose mechanisms of toxicity are related to its pro-oxidative properties. A previous report showed under in vivo conditions the neuroprotective effects of plants of the genus Polygala against MeHg-induced neurotoxicity. Moreover, the flavonoid quercetin, isolated from Polygala sabulosa, displayed beneficial effects against MeHg-induced oxidative damage under in vitro conditions. In this study, we sought for potential beneficial effects of quercetin against the neurotoxicity induced by MeHg in Swiss female mice. Animals were divided into six experimental groups: control, quercetin low dose (5 mg/kg), quercetin high dose (50 mg/kg), MeHg (40 mg/L, in tap water), MeHg+quercetin low dose, and MeHg+quercetin high dose. After the treatment (21 days), a significant motor deficit was observed in MeHg+quercetin groups. Biochemical parameters related to oxidative stress showed that the simultaneous treatment with quercetin and MeHg caused a higher cerebellar oxidative damage when compared to the individual exposures. MeHg plus quercetin elicited a higher cerebellar lipid peroxidation than MeHg or quercetin alone. The present results indicate that under in vivo conditions quercetin and MeHg cause additive pro-oxidative effects toward the mice cerebellum and that such phenomenon is associated with the observed motor deficit.