Evaluation of antibacterial activity and reversal of the NorA and MepA efflux pump of estragole against Staphylococcus aureus bacteria.

The antibacterial activity of the monoterpene estragole was evaluated against two strains of bacteria with an efflux pump mechanism, which are Staphylococcus aureus 1199B and S. aureus K2068, which have a NorA and MepA pump, respectively. For that, the methodology proposed by CLSI with modifications was followed, and to evaluate the reversal of the efflux pump, subinhibitory concentrations (MIC/8) of estragole and standard pump inhibitors, CCCP and Chlorpromazine were used and it was verified whether they managed to modulate the action of Norfloxacin, Ciprofloxacin and Ethidium Bromide, an indicator of an efflux pump. It was observed that estragole positively modulated norfloxacin and ethidium bromide against the strain of S. aureus 1199B and that it also managed to reduce the MIC of ethidium bromide against the strain of S. aureus K2068. In the non-clinical acute toxicity tests with estragole, the animals treated with the dose of 625 mg/kg/v.o. showed no clinical signs of toxicity, according to the parameters evaluated. These results are promising, since it places estragole as a possible inhibitor of the efflux pump, thus managing to inhibit this mechanism of action in the strains tested.

Myorelaxant Effect of the Dysphania ambrosioides Essential Oil on Sus scrofa domesticus Coronary Artery and Its Toxicity in the Drosophila melanogaster Model.

PURPOSE: Alternative methods for the use of animals in research have gained increasing importance, due to assessments evaluating the real need for their use and the development of legislation that regulates the subject. The principle of the 3R's (replacement, reduction and refinement) has been an important reference, such that in vitro, ex vivo and cord replacement methods have achieved a prominent place in research. METHODS: Therefore, due to successful results from studies developed with these methods, the present study aimed to evaluate the myorelaxant effect of the Dysphania ambrosioides essential oil (EODa) using a Sus scrofa domesticus coronary artery model, and the toxicity of both the Dysphania ambrosioides essential oil and its major constituent, α-terpinene, against Drosophila melanogaster in toxicity and negative geotaxis assays. RESULTS: The EODa relaxed the smooth muscle of swine coronary arteries precontracted with K+ and 5-HT in assays using Sus scrofa domesticus coronary arteries. The toxicity results presented LC50 values of 1.546 mg/mL and 2.282 mg/mL for the EODa and α-terpinene, respectively, thus showing the EODa and α-terpinene presented toxicity to these dipterans, with the EODa being more toxic. CONCLUSIONS: Moreover, the results reveal the possibility of using the EODa in vascular disease studies since it promoted the relaxation of the Sus scrofa domesticus coronary smooth muscle.

Evaluation of the antiedematogenic and anti-inflammatory properties of Ximenia americana L. (Olacaceae) bark extract in experimental models of inflammation.

Edema is one of the obvious indicators of inflammation and a crucial factor to take into account when assessing a substance's capacity to reduce inflammation. We aimed to evaluate the antiedematogenic and anti-inflammatory profile of the hydroethanolic barks extract of Ximenia americana (HEXA). The possible antiedematogenic and anti-inflammatory effect of EHXA (50, 100 mg/kg and 250 mg/kg v.o) was evaluated using the paw edema induced by carrageenan, zymosan, dextran, CFA and by different agents inflammatory (serotonin, histamine, arachidonic acid and PGE2), and pleurisy model induced by carrageenan and its action on IL-1ß and TNF-α levels was also evaluated. HEXA demonstrated a significant antiedematogenic effect at concentrations of 50, 100 and 250 mg/kg on paw edema induced by carrageenan, zymosan and dextran. However, the concentration of 50 mg/kg as standard, demonstrating the effect in the subchronic model, induced CFA with inhibition of 59.06 %. In models of histamine-induced paw edema, HEXA showed inhibition of - 30 min: 40.49 %, 60 min: 44.70 % and 90 min: 48.98 %; serotonin inhibition - 30 min: 57.09 %, 60 min: 66.04 % and 90 min: 61.79 %; arachidonic acid inhibition - 15 min: 36.54 %, 30 min: 51.10 %, 45 min: 50.32 % and 60 min: 76.17 %; and PGE2 inhibition - 15 min: 67.78 %, 30 min: 62.30 %, 45 min: 54.25 % and 60 min: 47.92 %. HEXA significantly reduced (p < 0.01) leukocyte migration in the pleurisy model and reduced TNF-α and IL-1ß levels in pleural lavage (p < 0.0001). The results showed that HEXA has the potential to have an antiedematogenic impact in both acute and chronic inflammation processes, with a putative mode of action including the suppression or regulation of inflammatory mediators.

Evaluation of the antifungal activity of α, ß, and δ-damascone and inclusion complexes in ß-cyclodextrin against Candida spp.

Due to the increase in fungal resistance to existing drugs, a need exists to search for new antifungals. This study aimed to evaluate the antifungal activity of α, ß, and δ-damascone and inclusion complexes with ß-cyclodextrin against different Candida spp. The inclusion complex of ß-damascone was prepared by the co-evaporation method using three molar proportions (1:1; 2:1; 3:1 (ßDA-ßCD)) and analyzed using Fourier transform infrared spectroscopy (FTIR). Standard Candida albicans (CA INCQS 40,006), Candida krusei (CK INCQS 40,095), and Candida tropicalis (CT INCQS 40,042) strains were used to evaluate antifungal activity. The substances were tested individually or in association with fluconazole (FCZ). The IC50 and cell viability curve constructions were performed using the microdilution method. The minimum fungicidal concentration (MFC) was determined by the subculture method in a solid medium. The α, ß, and δ-DA isolated or in combination with fluconazole (FCZ) showed significant antifungal activity. ß-damascone showed effective complexation in the three molar proportions assayed; however, none of the inclusion complexes was demonstrated clinically significant effects against the fungal tested. Then, all compounds have shown promising antifungal activities; however, in vivo assays are necessary to have therapeutical application in the future.

Mechanisms of Actions Involved in The Antinociceptive Effect of Estragole and its ß-Cyclodextrin Inclusion Complex in Animal Models.

(1) Background: estragole is a monoterpene found in the essential oils of several aromatic plants, which can be used for several pharmacological activities. The aim of this study was to evaluate the antinociceptive effect of estragole (Es) and its ß-cyclodextrins inclusion complex (Es/ß-CD). (2) Methods: the effects of Es and Es/ß-CD on the central nervous system (CNS) were evaluated through open field and rota-rod assays, and the antinociceptive effect in formalin models, abdominal writhing induced by acetic acid, hot plate, tail flick test and plantar mechanical hyperalgesia. (3) Results: Es and Es/ß-CD showed no alterations on the CNS evaluated parameters and the results suggested there was an antinociceptive action in the formalin, abdominal writhing, hot plate, tail flick tests and plantar mechanical hyperalgesia, proposing the involvement of the nitric oxide, glutamatergic signaling pathways, cyclic guanosine monophosphate and vanilloid pathways. (4) Conclusion: the results suggest that Es and Es/ß-CD have a promising antinociceptive potential as a possible alternative for the pharmacological treatment of pain, also showing that the encapsulation of Es in ß-cyclodextrins probably improves its pharmacological properties, since the complexation process involves much lower amounts of the compound, contributing to better bioavailability and a lower probability of adverse effect development.

Ximenia americana L. enhances the antibiotic activity and inhibit the development of kinetoplastid parasites.

OBJECTIVE: The objective of this work was evaluate the cytotoxic, leishmanicidal and tripanocidal activity, as well as to evaluate its antimicrobial and modulatory activity in association with different antibiotics of the hydroethanolic extract of the Ximenia Americana stem bark (EHXA). METHOD: In vitro tests against Trypanosoma cruzi, Leishmania sp. and citotoxicity were performed. The evaluation of the antibacterial and bacterial resistance modulatory effect was given by the microdilution method. RESULTS: The chemical profile show different classes of compounds with significant presence of quercetrin and caffeic acid. The EHXA demonstrated activity only in the concentration of 1000 µg/mL against the L. infantum and L. brasiliensis promastigotes, causing mortality percentage of 40.66 and 27.62%, respectively. The extract presented a significant toxicity only in the concentration of 1000 µg/mL, causing a mortality of 55.42% of fibroblasts. The antibacterial activity of the EHXA demonstrated a MIC value ≥1024 µg/mL against all the tested bacteria. However, in the modulation assay with EHXA in association with different antibiotics the extract had a synergistic effect against S. aureus strains when associated with norfloxacin. CONCLUSION: The results of this investigation demonstrate for the first time the chemical composition of the hydroethanolic extract of the Ximenia Americana stem bark, your potential antiparasitic and modulatory effect. The low cytotoxic and biological potential against S. aureus open therapeutic perspectives against leishmaniosis and bacterial infections.

HPLC profile and antiedematogenic activity of Ximenia americana L. (Olacaceae) in mice models of skin inflammation.

The aim of this study was to evaluate the anti-edematogenic activity of X. americana L. (HEXA) hydroethanolic extract in ear edema models (acute and chronic) induced by croton oil and by different phlogistic agents (arachidonic acid, capsaicin, phenol and histamine), identifying the possible anti-edematogenic mechanism. HEXA demonstrated a significant anti-edematogenic effect at concentrations of 100-500 µg/ear in ear edema induced by croton oil with higher inhibition of edema of 39.37. However, the concentrations of 100 and 200 µg/ear were taken as a standard, demonstrating the effect in the chronic model induced by croton oil with inhibition of 61.62% and 48.74%. In the AA-induced ear edema model, HEXA showed inhibition of: 24.45% and 32.31%; capsaicin inhibition of 72.72% and 47.57%; phenol inhibition of 34% and 20.1%; and histamine inhibition of 31.8% and 21.62%. Then, the results were showed that HEXA demonstrated an anti-edematogenic effect in acute and chronic inflammation models, demonstrating a probable mechanism of action by the inhibition or modulation of key mediators of the inflammatory process. The chemical profile and presence of flavonoids guaranteeing a profile of activity similar to natural drugs that act or modulate the production of mediators of inflammations.