Investigation of mechanisms of action involved in the antidepressant-like effect of Trans,trans-farnesol in mice.

This study aimed to investigate, through in vivo and biochemical methodologies, the effect of trans,trans-farnesol (12.5, 25, 50 or 100 mg/kg, p.o.) acute administration, adopting different behavioral and neurochemical parameters associated with an acute induced-depression model in mice. The initial results showed that, the oral treatment with trans,trans-farnesol, at the dose of 100 mg/kg induced a possible antidepressant-like effect in animals subjected to forced swim test (FST) and reserpine-induced akinesia. In addition, it was observed that the compound in question has an effect size and properties similar to imipramine (prototype of tricyclic antidepressants), but devoid of proconvulsant adverse effect. In biochemical assays, the pretreatment with trans,trans-farnesol, at a dose of 100 mg/kg (p.o.), decreased the hippocampal concentration of thiobarbituric acid reactive substances (TBARS) and restored striatal levels of noradrenaline and serotonin in mice subjected to FST. Altogether, these results suggest that trans,trans-farnesol showed a significant antidepressant-like effect, which seems to be mediated by the antagonism of muscarinic cholinergic receptors, reduction of oxidative stress and the modulation of noradrenaline and serotonin content in the central nervous system.

Possible mechanisms involved in the neuroprotective effect of Trans,trans-farnesol on pilocarpine-induced seizures in mice.

This study aimed to investigate, through in vivo and in vitro methodologies, the effect of acute trans,trans-farnesol (12.5, 25, 50 or 100 mg/kg, p.o.) administration on behavioral and neurochemical parameters associated with pilocarpine-induced epileptic seizure (300 mg/kg, i.p.) in mice. The initial results showed that the compound in question presents no anxiolytic-like or myorelaxant effects, despite reducing locomotor activity in the animals at all doses tested. In addition, the lowest dose increased the latency to onset of the first epileptic seizure, and the time to death. In addition to decreasing the mortality percentage in mice submitted to the pilocarpine model. In this same model, pretreatment with the lowest dose of the compound decreased the hippocampal concentrations of thiobarbituric acid and nitrite, and partially restored striatal concentrations of noradrenaline, dopamine, and serotonin. Taken together, the results suggest that trans,trans-farnesol presents a central depressant effect which contributes to its antiepileptic action which, in turn, seems to be mediated by the antagonism of muscarinic cholinergic receptors, reduction of oxidative stress. and modulation of noradrenaline, dopamine and serotonin concentrations in the central nervous system.

Hypoglycemic, Hypolipidemic, and Anti-Inflammatory Effects of Beta-Pinene in Diabetic Rats.

Background: Diabetes is a metabolic disease linked to multiple comorbidities, such as low-grade inflammation. ß-pinene, a monoterpene commonly found in aromatic plants, is endowed with anti-inflammatory effect and this fact lead us to investigate the possible hypoglycemic, hypolipidemic and anti-inflammatory effects of the monoterpene in the alloxan-induced diabetes experimental model. Methods: Male Wistar rats (200-250 g) were treated orally with ß-pinene (25, 50, 100, and 200 mg/kg) or glibenclamide (5 mg/kg), for seven consecutive days. Diabetes was induced by alloxan (40 mg/kg) through the penile vein. On the seventh day of treatment, blood samples were collected for biochemical analysis. The anti-inflammatory effect of ß-pinene was evaluated using the carrageenan-induced paw edema model, followed by the carrageenan-induced peritonitis. Results: The treatment with ß-pinene decreased plasma glucose, triglyceride, VLDL, LDL, and HDL levels, when compared to those of the control group. In addition, the association ß-pinene 10 mg/kg + glibenclamide 2 mg/kg significantly decreased blood glucose, total cholesterol, and triglyceride level. Finally, oral treatment with ß-pinene reduced carrageenan-induced paw edema and leukocyte migration in the peritoneum. Taken together, our results indicate that ß-pinene shows hypoglycemic and hypolipemic effects, which may involve some common mechanisms of glibenclamide. Besides, the monoterpene presented an anti-inflammatory action in diabetic rats that needs further investigation in order to clarify such effect and its correlation with the alterations observed in plasma parameters of ß-pinene-treated diabetic rats.

Vitamin D (VD3) antioxidative and anti-inflammatory activities: Peripheral and central effects.

Vitamin D (VD3, cholecalciferol), besides its role on bone calcium homeostasis, has also been shown to present anti-inflammatory actions. The objectives of the present work were to further extend these findings, focusing onVD3action mechanisms at the molecular level and onits central and peripheral effects. For that, VD3 antinociceptive and mainly anti-inflammatory activities were evaluated by acute models of nociception (formalin test) and inflammation (carrageenan-induced paw edema), in mice pretreated orally for 7 days with VD3 (0.5 and 1.0 mg/kg). Afterwards, the edematous paws were evaluated by immunohistochemical assays for TNF-alpha. In addition, brains from mice pretreated with VD3, at the same conditions, were harvested for iNOS andCOX-2 immunohistochemical (IHC) assays. The anti-inflammatory effect of VD3 on human neutrophil degranulation was evaluated by the release of myeloperoxidase (MPO) activity, as well as by the reactive oxygen species production. VD3 significantly reduced the licking time in the formalin test, at the second phase (inflammatory pain). VD3 also reduced the edema volume and the number of polymorphonuclear (PMN) cells, as well as the TNF-alpha expression in the edematous paws, compared with the control group. Furthermore, VD3 significantly decreased iNOS and COX-2 expressions in brain areas, such as hippocampus and prefrontal cortex, and inhibited the degranulation of activated neutrophils by the reduction of ROS production and MPO release. Based in these results, VD3 presents anti-inflammatory and antioxidative effects, manifested at peripheral and central sites as showed in the present work for the first time.

Antinociceptive activity of the Psidium brownianum Mart ex DC. leaf essential oil in mice.

Chronic pain management has several adverse effects and research looking for new and effective pain management drugs posing lower undesirable effects is necessary. Given the above, the pharmacological investigation of medicinal plants significantly contributes to the dissemination of plant-derived therapeutics. The aim of this study was to evaluate the antinociceptive activity of the Psidium brownianum Mart ex DC. leaf essential oil (PBEO) and the participation of the opioid pathway in this effect in mice. Swiss Mus musculus male mice were tested using acute nociception models (acetic acid induced abdominal contortions, formalin, capsaicin and hot plate tests). The possible myorelaxant action of the PBEO was tested using the rotarod test. The essential oil reduced animal nociception in chemical and heat models, with this action being devoid of a myorelaxant effect. Naloxone (2 mg/kg, intraperitoneally - i.p.) partially antagonized the PBEO activity, possibly acting via opioid receptors. The results obtained provide evidence that the traditional Psidium brownianum use may be effective for pain treatment.

Effects of the Hyptis martiusii Benth. leaf essential oil and 1,8-cineole (eucalyptol) on the central nervous system of mice.

The aim of this study was to characterize the central effects of the Hyptis martiusii leaf essential oil (OEHM) and 1,8-cineole (eucalyptol) using behavioral animal models. Gas chromatography coupled to mass spectrometry (GC/MS) was used to characterize the chemical compounds present in the OEHM. For the behavioral tests, female Swiss mice treated with the OEHM (25, 50, 100 and 200 mg/kg, i.p.) and 1,8-cineole (50 mg/kg, i.p.) were used and subjected to the following tests: open field, elevated cross maze, rotarod, sodium pentobarbital- or ethyl ether-induced sleep time, pentylenetetrazol-induced convulsions, haloperidol-induced catalepsy, and ketamine-induced hyperkinesia. GC/MS analysis identified 20 constituents with the majority of them being monoterpenes and sesquiterpenes, with eucalyptol (1,8-cineol), the major sample compound (25.93%), standing out. The results showed the OEHM (25, 50 100 and 200 mg/kg, i.p.) and its major compound (50 mg/kg, i.p.) reduced animal motility in the open field test, increased pentobarbital- and ethyl ether-induced sleep time, as well as death latency in the pentylenetetrazole-induced convulsion model. However, the tested compounds were devoid of anxiolytic-like and myorelaxant activity. In addition, the OEHM (100 and 200 mg/kg, i.p.) and 1,8-cineole (50 mg/kg, i.p.) potentiated haloperidol-induced catalepsy and reduced ketamine-induced hyperkinesia. Taken together, the results suggest the OEHM has important hypnotic-sedative and antipsychotic-like effects, which appear to be due to the monoterpene 1,8-cineole, the major compound identified in the essential oil.