Stigmasterol is a phytosterol that presents pharmacologic properties. However, its anti-inflammatory mechanism and antinociceptive effect are not yet elucidated. Thus, the present study aimed to investigate the anti-inflammatory and antinociceptive activities of stigmasterol and its mechanism of action in mice. The antinociceptive activity was assessed by the acetic acid-induced writhing test, formalin test, and hot plate test. The anti-inflammatory activity was investigated by carrageenan-induced peritonitis and paw edema induced by arachidonic acid. The involvement of glucocorticoid receptors in the mechanism of stigmasterol anti-inflammatory action was investigated by molecular docking, also by pretreating mice with RU-486 (glucocorticoid receptor antagonist) in the acetic acid-induced writhing test. Mice motor coordination was evaluated by the rota-rod test and the locomotor activity by the open field test. The lowest effective dose of stigmasterol was standardized at 10 mg/kg (p.o.). It prevented abdominal writhes and paw licking, but it did not increase the latency time in the hot plate test, suggesting that stigmasterol does not show an antinociceptive effect in response to a thermal stimulus. Stigmasterol decreased leukocyte infiltration in peritonitis assay and reduced paw edema elicited by arachidonic acid. Molecular docking suggested that stigmasterol interacts with the glucocorticoid receptor. Also, RU-486 prevented the effect of stigmasterol in the acetic-acid abdominal writhing test, which might indicate the contribution of glucocorticoid receptors in the mechanism of stigmasterol action. Stigmasterol reduced the number of crossings but did not impair mice's motor coordination. Our results show that stigmasterol presents anti-inflammatory effects probably mediated by glucocorticoid receptors.

No abstract

The increase in proinflammatory cytokine expression causes behavioral changes consistent with sickness behavior, and this led to the suggestion that depression might be a psychoneuroimmunological phenomenon. Here, we evaluated the effects of the pretreatment with fluoxetine (10 mg/kg, i.p.) and curcumin (0.5 mg/kg, i.p.) on the immune response elicited by the inoculation of an Aeromonas hydrophila bacterin in zebrafish. Nonpretreated but A. hydrophila-inoculated and sham-inoculated groups of fish served as controls. The social preference, locomotor, exploratory activities, and cerebral expression of il1b, il6, tnfa, and bdnf mRNA were compared among the groups. Behavioral changes characteristic of sickness behavior and a significant increase in the expression of il1b and il6 cytokines were found in fish from the immunostimulated group. The behavioral alterations caused by the inflammatory process were different between males and females, which was coincident with the increased expression of cerebral BDNF. Fluoxetine and curcumin prevented the sickness behavior induced by A. hydrophila and the increased expression of proinflammatory cytokines. Our results point to the potential of zebrafish as a translational model in studies related to neuroinflammation and demonstrate for the first time the effects of fluoxetine and curcumin on zebrafish sickness behavior.

In the present study, the antifungal activity and toxicity of the geranyl cinnamate ester (GCE) were investigated. The GCE showed antifungal activity at a minimum concentration of 0.16 μL/mL against Candida albicans and at concentrations greater than 2.5 μL/mL against Aspergillus niger. In acute toxicity studies, the administration of GCE (2.000 mg/kg) affected the body weight gain and food intake but did not induce the mortality of the animals studied. After the investigation of repeated-dose toxicity of GCE at 2 and 4 mg/kg, the hematological and biochemical parameters were changed. In addition, the adrenal weight of male mice treated with GCE at 4 mg/kg was affected. In conclusion, according to the Organization for Economic Cooperation and Development (OECD) acute toxicity parameters, the geranyl cinnamate ester can be classified into safety category number 5. The results of this study suggested that the geranyl cinnamate ester may be a source of natural antifungals.