Citrus essential oils inhalation by mice: Behavioral testing, GCMS plasma analysis, corticosterone, and melatonin levels evaluation.

The use of orange essential oils (EOs) as a complementary treatment is very common in Brazilian popular culture. The levels of melatonin (MEL) and corticosterone (CORT) hormones were investigated simultaneously, by the Luminex™ immunoassay system in mice plasma, after Citrus aurantium and Citrus sinensis EOs inhalation for 30 min. The plasma was analyzed by headspace through gas chromatography coupled to mass spectrometry for investigation of the EO components. Mice were submitted to behavioral testing to research anxiolytic-like, sedative, and antidepressant-like effects. The inhalation of atmosphere obtained from vaporization of 10% solution of this Citrus EO separately did not affect MEL or CORT plasma levels; that is, the MEL and CORT levels did not present variation in function of the EO in the schedule used. On the other hand, the imipramine positive control used altered the level of MEL as expected. The EO constituents were detected in plasma at different ratios that is present in inhaled EO. Behavioral tests showed that the inhalation of 10% C. sinensis EO presents an anxiolytic-like and sedative effect. Thus, C. sinensis EO can be a valuable tool for treatment of the anxiety disturbs, apparently without interference with MEL and CORT physiological levels.

The putative antipsychotic alstonine reverses social interaction withdrawal in mice.

Negative symptoms of schizophrenia are particularly problematic due to their deleterious impact on a patient's social life. The indol alkaloid alstonine, the major component of traditional remedies used for treating mental illnesses in Nigeria, presents a clear antipsychotic-like profile in mice, as well as anxiolytic properties. Considering that social interaction is the core of negative symptoms, and that anxiolytic drugs can improve social interaction behavior, the aim of this study was to evaluate the effects of alstonine in the social interaction and MK801-induced social withdrawal models in mice. Sub-chronic (but not acute) treatment with alstonine 0.5 mg/kg (but not 1.0 mg/kg) significantly increased social interaction in mice. Moreover, MK801-induced social withdrawal was completely prevented by sulpiride (10 mg/kg) and alstonine 1.0 mg/kg, and partially prevented by alstonine 0.5 mg/kg. The study indicates that alstonine not only increases social interaction in normal mice, but also averts social deficits attributable to negative symptoms of schizophrenia. This study reinforces and complements the antipsychotic-like profile of alstonine, and emphasizes its potential as a drug useful for the management of negative symptoms in schizophrenia.

Synthesis of all low-energy stereoisomers of the tris(pyrrolidinoindoline) alkaloid hodgkinsine and preliminary assessment of their antinociceptive activity.

The previously unknown stereoisomers 3, 4, ent-1, and ent-4 of the tris(pyrrolidinoindoline) alkaloids hodgkinsine (1) and hodgkinsine B (2) were prepared by stereocontrolled total synthesis. In each synthesis, a catalyst-controlled intramolecular Heck reaction was the key step in appending a third cis-pyrrolidinoindoline ring to a hexacyclic chimonanthine precursor. Results of the preliminary evaluation of these hodgkinsine stereoisomers in the tail flick and capsaicin pain models are reported.