Nootkatone (NTK) is a sesquiterpenoid found in essential oils of many species of
(Rutaceae). Considering previous reports demonstrating that NTK inhibited inflammatory signaling pathways, this study ...aimed to investigate the effects of this compound in mice models of acute and chronic inflammation. Murine models of paw edema induced by carrageenan, dextran, histamine, and arachidonic acid, as well as carrageenan-induced peritonitis and pleurisy, were used to evaluate the effects of NTK on acute inflammation. A murine model of granuloma induced by cotton pellets was used to access the impact of NTK treatment on chronic inflammation. In the acute inflammation models, NTK demonstrated antiedematogenic effects and inhibited leukocyte recruitment, which was associated with decreased vascular permeability, inhibition of myeloperoxidase (MPO), interleukin (IL)1-β, and tumor necrosis factor (TNF)-α production. In silico analysis suggest that NTZ anti-inflammatory effects may also occur due to inhibition of cyclooxygenase (COX)-2 activity and antagonism of the histamine receptor type 1 (H
). These mechanisms might have contributed to the reduction of granuloma weight and protein concentration in the homogenates, observed in the chronic inflammation model. In conclusion, NTK exerted anti-inflammatory effects that are associated with inhibition of IL1-β and TNF-α production, possibly due to inhibition of COX-2 activity and antagonism of the H1 receptor. However, further studies are required to characterize the effects of this compound on chronic inflammation.
Staphylococcus aureus
is known to be a human pathogen and is often resistant to antibiotics, so there is a demand for new treatment alternatives that have the ability to reverse such resistance. The ...present study aimed to evaluate the antibacterial action and reversal of the efflux pump activity of the compounds Isopulegol (ISO) and its β-cyclodextrin inclusion complex (ISO/β-CD) in
S. aureus
strains carrying an efflux pump. (MsrA, TetK, NorA and MepA). The complex was obtained using the paste complexation method. The minimum inhibitory concentration (MIC) of ISO and ISO/β-CD was determined for the evaluation of antibacterial activity against multiresistant strains of
S. aureus
(RN4220, IS-58, 1199, 1199B and K2068) and the compounds showed a minimum inhibitory concentration (MIC) ≥ 1024 μg/mL. Modulation assays were performed using ISO and ISO/β-CD, which associated with antibiotics and Ethidium Bromide (EtBr) showed synergism and MIC reduction in some of the tested bacteria. Therefore, it can be concluded that the isolated compounds ISO and ISO/β-CD are effective in inhibiting the efflux pump mechanism against some of the tested strains; with modulation, only strains IS-58, SA 1199 and K2068 showed a MIC decrease effect, while all strains showed a reduction in MIC with ethidium bromide.
Antiedematogenic and Analgesic Activities of Abietic Acid in Mice Lima Silva, Maria Gabriely; Santos da Silva, Lucas Yure; Torres Pessoa, Renata ...
Chemistry & biodiversity,
December 2023, 2023-Dec, 2023-12-00, 20231201, Letnik:
20, Številka:
12
Journal Article
Recenzirano
Odprti dostop
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.
The species Croton rhamnifolioides, belonging to the Croton genus, is known in ethnomedicine as “quebra faca” and is used in the treatment of stomach pain, vomiting and fever. This study aims to ...evaluate the anti-edematogenic and anti-inflammatory effect of Croton rhamnifolioides leaf essential oil (OEFC) and its major constituent: 1,8-cineole (eucalyptol). The essential oil was extracted from fresh leaves through a hydrodistillation system. The chemical analysis was determined by gas chromatography-mass spectrometry (GC–MS). The acute anti-inflammatory activity was determined from the models of: ear edema by the single application of croton oil, paw edema induced by: carrageenan, dextran, histamine and arachidonic acid, while vascular permeability was determined by Evans blue extravasation and chronic anti-inflammatory activity by granuloma induction using the implantation of cotton pellets. The GC–MS results identified and quantified 11 constituents, with the major component being 1,8-cineole (41.33%). The OEFC (20mg/mL) and 1,8-cineole (8.26mg/mL) significantly reduced the edema induced by croton oil by 42.1 and 34.9%, respectively. The OEFC (25, 50, 100 and 200mg/kg) and 1,8-cineole (10.33, 20.66, 41.33 and 82.66mg/kg) statistically reduced paw edema induced by carrageenan, dextran as well as vascular permeability (protein extravasation). The OEFC (25mg/kg) and 1,8-cineole (10.33mg/kg) demonstrated efficacy in reducing edema induced by histamine and arachidonic acid and granuloma. In conclusion, the OEFC and 1,8-cineole have anti-inflammatory activity in the acute and chronic phase, suggesting therapeutic potential as a source for the development of new anti-inflammatory agents.
This work aimed to analyze the chemical composition and evaluate the anti-inflammatory and antinociceptive properties of the essential oil obtained from the leaves of
Lantana montevidensis
(OEFLM) in ...mice. The chemical composition of the OEFLM was analyzed by GC–MS, and its effects on the central nervous system were determined by the open field and rotarod tests. The antinociceptive and anti-inflammatory screenings were conducted using the formalin test, as well as the acetic acid-induced abdominal contortion assay. The antinociceptive activity was assessed by the tail-flick and hot plate tests. The systemic anti-inflammatory activity was determined using models of paw edema induced by carrageenan, dextran, histamine, or arachidonic acid. The effects of the essential oil on vascular permeability and granuloma formation were also investigated. The chemical composition of the OEFLM revealed the presence of valencene (17.93%), bicyclogermacrene (16.35%), trans-caryophyllene (12.84%) and germacrene D (12.18%). The administration of OEFLM at the dose of 2000 mg/Kg caused no evident toxicity. While OEFLM (25, 50, 100, and 200 mg/kg) did not present significant anxiolytic-loke or sedative effects, it showed promising antinociceptive and anti-inflammatory activities. The results of this study indicate that the OEFLM has analgesic and anti-inflammatory activities in animal models by inhibiting acute and chronic inflammation.
Ximenia americana L., popularly known in Brazil as “ameixa do-mato, ameixa-brava, and ameixa-do-sertão,” is widely used in folk medicine to treat several intestinal disorders. The present study ...assessed the potential mechanisms of action underlying the gastroprotective activity of the hydroethanolic extract of Ximenia americana L. (EHXA) stem bark. The acute toxicity of EHXA was estimated, and later, the gastroprotective effect in mice was assessed through acute models of gastric lesions induced by acidified or absolute ethanol and indomethacin, where the following mechanisms were pharmacologically analyzed: the involvement of prostaglandins (PG), histamine (H2) receptors, ATP-dependent potassium channels, sulfhydryl groups (SH), α2 adrenergic receptors, nitric oxide (NO), myeloperoxidase (MPO), gastric mucus production, and acetylcholine-mediated intestinal motility. Regarding toxicity, EHXA did not cause deaths or signs of toxicity (LD50 greater than or equal to 2000 mg/kg/p.o.). When the gastroprotective effect was assessed, EHXA (50, 100, and 200 mg/kg/p.o.) reduced the rate of lesions induced by acidified ethanol by 65.63; 53.66, and 58.02% in absolute ethanol at 88.91, 78.82, and 74.68%, respectively, when compared to the negative control group. In the indomethacin-induced gastric injury model, the reductions were 84.69, 55.99, 55.99, and 42.50%, respectively. The study revealed that EHXA might stimulate mucus production and reduce intestinal motility through SH groups, NO production, and activation of α2 adrenergic receptors. The results indicated that EHXA had significant gastroprotective activity in the evaluated models. However, further investigation is required to elucidate the cellular and molecular events underlying the action of EHXA components and to correlate them with the modulation of the signaling pathways, as demonstrated by the current pharmacological approach. Therefore, the results demonstrated in the present study, as well as previously reported findings, support the recommendation of using this species in traditional communities in Brazil.
Leishmaniasis and Chagas disease are neglected tropical diseases with relevance and public interest. Currently, the search for antiparasitic agents from medicinal plants has been the target of great ...research.
Croton rhamnifolioides
Pax. & K. Hoffm is known in popular medicine as “quebra-faca” or “caatinga-branca” and is used to treat stomachache, vomiting and fever. The aim of this study was to evaluate the cytotoxic potential and antiparasitic activity of the
Croton rhamnifolioides
Pax leaves. & K. Hoffm essential oil (EOCr) and its inclusion complex with β-cyclodextrin (EOCr/β-CD). The trypanocide, leishmanicidal and cytotoxicity activity investigations were performed in triplicates by in vitro cell culture assays using different EOCr (1000, 500, 250, 125, 62.5 μg/mL) and EOCr/β-CD (1000, 500 and 250 μg/mL) concentrations dissolved in dimethyl sulfoxide. The results showed the EOCr and EOCr/β-CD possessed an inhibitory potential with IC
50
values of 85.21 and 1823 μg/mL against
T. cruzi
, IC
50
values of 127.43 and 354.568 μg/mL against
Leishmania braziliensis
and IC
50
values of 111.84 and 923.56 μg/mL against
Leishmania infantum
, respectively, with the EOCr being the most effective against
T. cruzi
. The EOCr presented toxic effects against NCTC929 fibroblasts at the highest concentrations of 1000 and 500 μg/mL, obtaining an IC
50
value of 338.84 μg/mL; however, the EOCr/β-CD showed no signs of significant cytotoxicity obtaining an IC
50
greater than 1000 μg/mL. The current results suggest the
C. rhamnifolioides
essential oil presents significant results, thus representing an alternative source for the development of natural products with antiparasitic activity.
(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 β-cyclodextrins inclusion complex (Es/β-CD). (2) Methods: the effects of Es and Es/β-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/β-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/β-CD have a promising antinociceptive potential as a possible alternative for the pharmacological treatment of pain, also showing that the encapsulation of Es in β-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.
This study aims to evaluate the antinociceptive effect of the C. rhamnifolioides leaf essential oil (OEFC) and the β-cyclodextrin inclusion complex (COEFC) and investigate the pain signaling pathways ...involved in the antinociceptive response. The effects of the OEFC and COEFC on the central nervous system (CNS) were determined by open field and rota-rod assays, and the antinociceptive effect was evaluated via the acetic acid-induced abdominal contortions, formalin, and hot plate models. Swiss (Mus musculus) male mice (20–30 g) were used in both trials. The OEFC (200 mg/kg/v.o-orally) and COEFC (83.5 mg/kg/v.o.) did not present alterations in the CNS. The OEFC (25, 50, 100, and 200 mg/kg/vo.) and COEFC (8.35, 41.75, and 83.5 mg/kg/v.o.) demonstrated antinociceptive effects in the abdominal contortions, formalin, and hot plate tests. The OEFC (25 mg/kg/v.o.) and COEFC (8.35 mg/kg/v.o.) doses showed that the antinociceptive effect involves the activation of the opioid, cholinergic, and vanilloid systems, as well as the L-arginine/NO and α-2 adrenergic receptor pathways. The antinociceptive potential the OEFC and COEFC demonstrate possible alternatives for the therapy of pain. However, the COEFC presented more significant effects at lower doses than the isolated OEFC, where this action may be justified by the properties and advantages of the complexation.
Croton rhamnifolioides is used in popular medicine for the treatment of inflammatory diseases. The objective of this study was to characterize and evaluate the anti-inflammatory effect of C. ...rhamnifolioides essential oil complexed in β-cyclodextrin (COEFC). The physicochemical characterization of the complexes was performed using different physical methods. The anti-inflammatory activity was evaluated in vivo by ear edema, paw edema, cotton pellet-induced granuloma, and vascular permeability by Evans blue extravasation. The mechanism of action was validated by molecular docking of the major constituent into the cyclooxygenase-2 (COX-2 enzyme). All doses of the COEFC reduced acute paw edema induced by carrageenan and dextran, as well as vascular permeability. Our results suggest the lowest effective dose of all samples inhibited the response induced by histamine or arachidonic acid as well as the granuloma formation. The complexation process showed that the pharmacological effects were maintained, however, showing similar results using much lower doses. The results demonstrated an involvement of the inhibition of pathways dependent on eicosanoids and histamine. Complexation of β-cyclodextrin/Essential oil (β-CD/EO) may present an important tool in the study of new compounds for the development of anti-inflammatory drugs.
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