Antifungal Activity and Acute and Repeated-Dose Toxicity Study of Geranyl Cinnamate Ester in Mice.

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.

Investigation of the anti-inflammatory effects of stigmasterol in mice: insight into its mechanism of action.

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.

Anti-Inflammatory Effects of Campomanesia xanthocarpa Seed Extract Obtained from Supercritical CO2.

Campomanesia xanthocarpa is a plant species traditionally used in the treatment of diabetes, fever, hypercholesterolemia, obesity, and urinary tract diseases. The anti-inflammatory effects of C. xanthocarpa leaves in mice were already known. Nevertheless, studies on the anti-inflammatory activity of its seeds are still lacking. The aim of this study was to investigate the anti-inflammatory activity and acute toxicity of C. xanthocarpa seed extract, obtained from supercritical CO2 extraction (SCCO2) at 40°C and 250 bar, in mice. GC/MS analysis revealed that ß-caryophyllene is the major compound present in the C. xanthocarpa SCCO2 extract. The extract (60 mg/kg, p.o.) significantly reduced the nociceptive behavior in the second phase of the formalin test and prevented the paw oedema induced by carrageenan up to 6 h after carrageenan injection. The extract (0.1-1 µg/mL) inhibited neutrophils migration induced by LPS from E. coli in vitro. This antichemostatic effect was comparable to the effect of indomethacin. Acute administration (2000 mg/kg, p.o.) of C. xanthocarpa SCCO2 extract caused no mice mortality, demonstrating that the extract is devoid of acute toxicity. These data suggest that C. xanthocarpa seeds present anti-inflammatory activity and represent a source of anti-inflammatory compounds.

Antinociceptive effect and mechanism of supercritical carbon dioxide extract of Aloysia gratissima leaves in mice.

BACKGROUND: A. gratissima is a shrub used in folk medicine as analgesic and sedative. However, studies on its antinociceptive activity are scarce. This research aimed to evaluate the antinociceptive effect of a supercritical carbon dioxide (SCCO2) extract of A. gratissima leaves (EAG) in mice. METHODS: A. gratissima leaves were subjected to extraction with supercritical CO2 (60 °C, 200 bar). The chemical composition of EAG was determined by gas chromatography-mass spectrometry (GC-MS). The antinociceptive profile of the extract (1, 10 and 30 mg/kg, p.o.) was established using acetic acid-induced abdominal contraction tests and formalin-induced paw-licking tests. The open field and rota-rod tests were used to evaluate a possible interference of EAG on mice motor performance. The contribution of the opioid system and adenosine triphosphate (ATP) sensitive K+ channels in the mechanism(s) of EAG action was evaluated by specific receptor blockers. EAG's acute toxicity was investigated using OECD 423 guideline. RESULTS: The GC-MS revealed the presence of sesquiterpenes (guaiol and pinocamphone) in the EAG. Doses of 10 mg/kg and 30 mg/kg significantly reduced the number of abdominal writhes and paw licking time in mice in the formalin test. The EAG did not affect the locomotor activity and motor coordination of the mice. The antinociceptive effect of the EAG was prevented by glibenclamide in the mice formalin test, unlike naloxone pre-treatment. The acute administration of EAG caused no mortality. CONCLUSION: A. gratissima leaves possess antinociceptive effect, mediated by K+ channels sensitive to ATP.