This study aimed to identify the chemical composition of the
aqueous leaf and root extracts (EALST and EARST) and to evaluate their effect, comparatively, against opportunistic pathogenic fungi. ...Ultra-Performance Liquid Chromatography Coupled to a Quadrupole/Time of Flight System (UPLC-MS-ESI-QTOF) was employed for chemical analysis.
and
standard strains and clinical isolates were used (CA INCQS 40006, CT INCQS 40042, CA URM 5974, and CT URM 4262). The 50% Inhibitory Concentration for the fungal population (IC
) was determined for both the intrinsic action of the extracts and the extract/fluconazole (FCZ) associations. The determination of the Minimum Fungicidal Concentration (MFC) and the verification of effects over fungal morphological transitions were performed by subculture in Petri dishes and humid chambers, respectively, both based on micro-dilution. UPLC-MS-ESI-QTOF analysis revealed the presence of phenolic and flavonoid compounds. The association of the extracts with fluconazole, resulted in IC
values from 2.62 µg/mL to 308.96 µg/mL. The MFC of the extracts was ≥16,384 µg/mL for all tested strains, while fluconazole obtained an MFC of 8192 µg/mL against
strains. A reduction in MFC against CA URM 5974 (EALST: 2048 µg/mL and EARST: 1024 µg/mL) occurred in the extract/fluconazole association.
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.
Exacerbated inflammatory responses to harmful stimuli can lead to significant pain, edema, and other complications that require pharmacological intervention. Abietic acid (AA) is a diterpene found as ...a significant constituent in pine species, and evidence has identified its biological potential. The present study aimed to evaluate abietic acid‘s antiedematogenic and anti‐inflammatory activity in mice. Swiss mice (Mus musculus) weighing 20–30 g were treated with AA at 50, 100, and 200 mg/kg. The central nervous system (CNS) effects were evaluated using open‐field and rotarod assays. The antinociceptive and anti‐inflammatory screening was assessed by the acetic acid and formalin tests. The antiedematogenic activity was investigated by measuring paw edema induced by carrageenan, dextran, histamine, arachidonic acid, and prostaglandin, in addition to using a granuloma model. The oral administration of abietic acid (200 mg/Kg) showed no evidence of CNS effects. The compound also exhibited significant antiedematogenic and anti‐inflammatory activities in the carrageenan and dextran models, mostly related to the inhibition of myeloperoxidase (MOP) activity and histamine action and, to a lesser extent, the inhibition of eicosanoid‐dependent pathways. In the granuloma model, abietic acid‘s effect was less expressive than in the acute models investigated in this study. In conclusion, abietic acid has analgesic and antiedematogenic activities related to anti‐inflammatory mechanisms.
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, β, and δ-damascone and inclusion ...complexes with β-cyclodextrin against different Candida spp. The inclusion complex of β-damascone was prepared by the co-evaporation method using three molar proportions (1:1; 2:1; 3:1 (βDA-βCD)) 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 IC
50
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, β, and δ-DA isolated or in combination with fluconazole (FCZ) showed significant antifungal activity. β-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.
•Microencapsulation influenced positively green tea stability.•GTM presented a higher antioxidant activity.•GTM was effective against gram-positive microorganism.•GTM administration reduced locomotor ...activity in zebrafish.
This work aimed to characterize the physical-chemical properties, antimicrobial activity, and toxicity of microcapsules elaborated on the combination of green tea (Camelia sinensis) extract with cashew gum and maltodextrin. It was observed that the encapsulation process influenced positively the physical-chemical characteristics of green tea extract (GTE) once green tea microcapsules (GTM) presented values equal to 1.42, 3.66 and 0.36 for humidity, hygroscopicity, respectively, which can be correlated to an increase in GTE stability. GTM exhibited values of 14,950.4 mg GAE/100 g and 1188.4 μMTrolox.g−1 for phenolics and antioxidant activity, respectively, as well as presented an antimicrobial effect against the gram-positive bacteria. No toxicity effect was observed against zebrafish (Danio rerio) but sample administration resulted in a reduction in the locomotor activity of the animals. This study provided valuable information regarding the encapsulation process as an effective tool for increasing the application of green tea extract, considering its antioxidant and antimicrobial properties, reinforcing its safety for consumers.
•The extract of Z. joazeiro Mart. leaves (EEFZJ) showed the presence of flobabenic tannins, leucoanthocyanidins, flavonois, flavonones.•There was no clinically relevant antibacterial activity, but ...the extract showed synergistic.•This extract was non toxic and evidenced sedative effect in adult zebrafish.•That Z. joazeiro has potential as an alternative plant-derived of phytomedicines against resistant bacterial infections and anxiolytic therapy.
Ziziphus joazeiro Mart. is an endemic plant of the Caatinga that presents a great socioeconomic importance for the Northeast and Semiarid Region of Brazil. In view of this, this study aimed to evaluate the antibacterial activity and anxiolytic-like effects of Ziziphus joazeiro Mart leaves in adult zebrafish (Danio rerio). The characterization of the main classes of metabolites was performed through chemical reactions. The antibacterial and antibiotic potentiating activity was evaluated by broth microdilution assays. The 96 h acute toxicity, open field test and anxiety models test was evaluated in vivo on adult zebrafish. The results obtained in the phytochemical prospection evidenced the presence of flobabenic tannins, leucoanthocyanidins, flavonois, flavonones, catechins, alkaloids, steroids, and triterpenoids. EEFZJ did not show antibacterial activity for all microorganism tested (MIC ≥ 1024 µg/mL), but reduced the concentration required for bacterial growth inhibition in combination with gentamicin and norfloxacin against multidrug-resistant strains of S. aureus (SA10) and E. coli (EC06), exhibiting synergistic effect with these antibiotics (p<0.0001). In the tests in vivo, EEFZJ was found to be nontoxic, performing reduced locomotor activity and demonstrated an anxiolytic-like effect in adult zebrafish via GABAergic and Serotoninergic systems (5-HT1, 5-HT2A/2C and 5-HT3A/3B).
The zebrafish (
Danio rerio
) has been proposed as a low-cost and simple alternative to the use of higher vertebrates in laboratory research on novel compounds with antinociceptive potential. In this ...study, we tested adult zebrafish (
Danio rerio
) as an alternative behavioral model of formalin-induced nociception. We evaluated the nociceptive effect of 0.1% formalin (3 or 5 μL; intramuscularly i.m.), applied into the tail or lips, on locomotor activity, using as parameter the number of times the fish crossed the lines between the quadrants of a glass Petri dish during the neurogenic stage (0–5 min) and the inflammatory stage (15–30 min). The behavioral model was validated by testing the antinociceptive effect of morphine and indomethacin (standard analgesic drugs used in the formalin test of rodents). We also tested whether the effect of morphine could be modulated by naloxone, an opioid antagonist. The effect of morphine and indomethacin on zebrafish locomotor behavior was evaluated with the open field test. The white/black test was used to rule out the anxiolytic effect of 0.1% formalin injected into the tail on adult zebrafish. Formalin (0.1%; 3 and 5 μL injected into the tail) increased significantly the nociceptive behavior of the adult zebrafish in both stages (
p
< 0.001 vs. control). Morphine and indomethacin (both 0.2 mg/mL; 20 μL; intraperitoneally i.p.) significantly inhibited nociception induced with formalin (5 μL injected i.m. into the tail) in both stages (
p
< 0.001). Naloxone blocked the antinociceptive effect of morphine. No influence on locomotion was observed. Locally administered formalin (injected into the tail) induced nociception, but not anxiety. The results suggest that the adult zebrafish behavioral model is a feasible alternative to more conventional laboratory models used in research on novel compounds with antinociceptive potential.
The GABAergic and serotoninergic neurotransmission pathways are involved in the control of anxiety and ensure emotional balance. Some plant species have substances with anxiolytic activity, a ...therapeutic effect associated with the presence of phenolic compounds.
Before assessing the existence of anxiolytic activity, ethanolic extracts from leaves, branches and roots of Ziziphus cotinifolia Reissek were evaluated regarding biological activity and absence of toxicity. Later the influences of the samples on locomotor and anxiolytic activity, anxiolytic pathways and probable mechanisms of neurotransmission were evaluated.
The EEtFJ extract (0.5 mg/mL) did not have its anxiolytic activity reversed by the GABAergic receptor antagonist (Fmz + EEtFJ = EEjFJ; p<0.05). The twig extracts and flumazenil only partially reduced the time spent in the light zone (Fmz + EEtGJ < + EEtGJ; p<0.05), the root extract was not reversed by flumazenil (Fmz + EEtFRJ = EEtFRJ).
The initial analysis data reveal the presence of phenolic compounds that explain the biological activities found and, as they act on different targets of neurotransmission systems involved in the control of anxiety disorders, they have potential for the production of herbal medicines with synergistic action.
This study aimed to test for the possible antinociceptive effect of the naturally occurring terpene citral in rodent models of acute and chronic orofacial pain and to test for the possible ...involvement of transient receptor potential (TRP) channels in this effect. Acute nociceptive behavior was induced in one series of experiments by administering formalin, cinnamaldehyde, menthol or capsaicin to the upper lip. Nociceptive behavior was assessed by orofacial rubbing, and the effects of pre-treatment with citral (0.1, 0.3 or 1.0 mg/Kg) or vehicle (control) were tested on the behavior. Nociceptive behavior was also induced by formalin injected into the temporomandibular joint or mustard oil injected into the masseter muscle, preceded by citral or vehicle (control) treatment. The chronic pain model involved infraorbital nerve transection (IONX) that induced mechanical hypersensitivity which was assessed by von Frey hair stimulation of the upper lip. Motor activity was also evaluated. Docking experiments were performed using TRPV1 and TRPM8 channels. Citral but not vehicle produced significant (p<0.01, ANOVA) antinociception on all the acute nociceptive behaviors, and these effects were attenuated by TRPV1 antagonist capsazepine, TRPM3 antagonist mefenamic acid and by TRPM8 desensitization, but not by ruthenium red and TRPA1 antagonist HC-030031. The IONX animals developed facial mechanical hypersensitivity that was significantly reduced by citral but not by vehicle. The docking experiments revealed that citral may interact with TRPV1 and TRPM8 channels. These results indicate the potential use of citral as an inhibitor of orofacial nociception in both acute and chronic pain states through TRPV1, TRPM3 and TRPM8 channels.
See also Figure 1
(Fig. 1)
.
This study aimed to evaluate the antinociceptive effect of sulphated polysaccharide from the marine algae
Hypnea pseudomusciformis
(PLS) using rodent models of orofacial pain. Acute pain was induced ...by formalin, capsaicin, cinnamaldehyde, acidified saline or glutamate (cutaneous modes) and hypertonic saline (corneal model). In one experiment, animals were pretreated with ruthenium red, glibenclamide, naloxone, L-NAME, methylene blue or ketamine to investigate the mechanism of antinociception. In another experiment, animals pretreated with PLS or saline were submitted to the temporomandibular joint formalin test. In yet another, animals were submitted to craniofacial pain induced by mustard oil. Motor activity was evaluated with the open-field test. Cytotoxicity and antioxidant activities were also assessed. Pre-treatment with PLS significantly reduced nociceptive behavior associated with acute pain. Antinociception was effectively reduced, but not inhibited, by ruthenium red and ketamine. L-NAME and glibenclamide enhanced the PLS effect. PLS antinociception was resistant to methylene blue, naloxone and heating. PLS presented no cytotoxicity or antioxidant properties. Our results confirm the potential pharmacological relevance of PLS as an inhibitor of orofacial nociception in acute pain probably mediated by glutamatergic, nitrergic, TRPs and K + ATP pathways.
