Topical Antiedematogenic Activity of the Essential Oil of Psidium brownianum Mart. (OEPB) in Murine Ear Edema Models.

Psidium brownianum Mart is reported in the literature by antinociceptive and antioxidant activities, indicating that this species' secondary metabolites might be used to control inflammatory processes. The present study aimed to characterize the topical antiedematogenic activity of the essential oil of Psidium brownianum Mart. (OEPB) in ear edema models by different inflammatory agents. Female Swiss mice (25-35 g) and Wistar albino rats (200-300 g) were used throughout tests (n=6/group) on acute or chronic edema models induced by single and multiple topical applications. The OEPB is administered topically pure or at a concentration of 100 or 200 mg/mL. The antiedematogenic mechanism of OEPB was analyzed by administering capsaicin, arachidonic acid, histamine, and phenol at the best effective dose (200 mg/mL). The results showed a significant reduction of edema-induced single (28.87 %) and multiple (50.13 %) applications of croton oil compared to the negative control group. Regarding potential mechanisms of action, OEPB (200 mg/mL) inhibited the development of edema triggered by capsaicin (29.95 %), arachidonic acid (22.66 %), phenol (23.35 %), and histamine (75.46 %), suggesting an interference with the histaminergic pathway. These results indicate that OEPB presents a topical antiedematogenic effect in acute and chronic murine models, possibly interfering with inflammatory pathways triggered by mediators such as histamine.

Assessing dental surgeons' understanding of bisphosphonates: Implications for patient health in oral surgery.

Objectives: This study aimed to analyze the knowledge of dental surgeons concerning the pharmacological effects of bisphosphonates (BP) and their impact on the health of patients undergoing oral surgery treatment. Materials and methods: A quantitative study was conducted with professionals in the Cariri region of Ceará, Brazil. The data were collected using a semi-structured questionnaire to interview the dental surgeons who met the inclusion criteria. The data were analyzed by Chi-square and Fischer's Exact tests using the SPSS program version 22.0. Results: The results indicated that most interviewed subjects have no experience with the dental treatment of individuals under treatment with bisphosphonates. When a sample of the medication was presented, a significant number of the participants (65.3%) did not recognize the drug. Among those who recognized it, 66.5% did not know how to treat bisphosphonate-using patients in the clinical routine. However, 95.1% of the professionals who recognized the need to discontinue these drugs admitted contacting the prescriber to establish the best dental conduct. Our results also showed that recently graduated professionals better understood the need to stop BP use before invasive treatment, although they did not know the protocol. Conclusion: In conclusion, a better knowledge of the pharmacological effects of BP is crucial for conducting adequate anamnesis, requesting additional tests, and performing medical monitoring, which has a significant impact on the clinical practice of dental surgeons.

Valencene, Nootkatone and Their Liposomal Nanoformulations as Potential Inhibitors of NorA, Tet(K), MsrA, and MepA Efflux Pumps in Staphylococcus aureus Strains.

Valencene and nootkatone are aromatic sesquiterpenes with known biological activities, such as antimicrobial, antioxidant, anti-inflammatory, and antitumor. Given the evidence that encapsulation into nanosystems, such as liposomes, could improve the properties of several compounds, the present study aimed to evaluate the activity of these sesquiterpenes in their isolated state or in liposomal formulations against strains of Staphylococcus aureus carrying efflux pumps. The broth microdilution method evaluated the antibiotic-enhancing activity associated with antibiotics and ethidium bromide (EtBr). The minimum inhibitory concentration was assessed in strains of S. aureus 1199B, IS-58, and RN4220, which carry the efflux proteins NorA, Tet(K), and MsrA. In tests with strain 1199B, valencene reduced the MIC of norfloxacin and EtBr by 50%, while the liposomal formulation of this compound did not show a significant effect. Regarding the strain IS-58, valencene, and its nanoformulation reduced norfloxacin MIC by 60.3% and 50%, respectively. In the non-liposomal form, the sesquiterpene reduced the MIC of EtBr by 90%. Against the RN4220 strain, valencene reduced the MIC of the antibiotic and EtBr by 99% and 93.7%, respectively. Nootkatone and its nanoformulation showed significant activity against the 1199B strain, reducing the EtBr MIC by 21.9%. Against the IS-58 strain, isolated nootkatone reduced the EtBr MIC by 20%. The results indicate that valencene and nootkatone potentiate the action of antibiotics and efflux inhibitors in strains carrying NorA, Tet(K), and MsrA proteins, which suggests that these sesquiterpenes act as efflux pump inhibitors in S. aureus. Therefore, further studies are needed to assess the impact of incorporation into liposomes on the activity of these compounds in vivo.

Antiedematogenic and Analgesic Activities of Abietic Acid in Mice.

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.

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.

Antibacterial Activity of the Essential Oil of Piper tuberculatum Jacq. Fruits against Multidrug-Resistant Strains: Inhibition of Efflux Pumps and ß-Lactamase.

Antimicrobial resistance has become a growing public health concern in recent decades, demanding a search for new effective treatments. Therefore, this study aimed to elucidate the phytochemical composition and evaluate the antibacterial activity of the essential oil obtained from the fruits of Piper tuberculatum Jacq. (EOPT) against strains carrying different mechanisms of antibiotic resistance. Phytochemical analysis was performed using gas chromatography-mass spectrometry (GC/MS). The antibacterial activity of EOPT and its ability to inhibit antibiotic resistance was evaluated through the broth microdilution method. The GC-MS analysis identified 99.59% of the constituents, with ß-pinene (31.51%), α-pinene (28.38%), and ß-cis-ocimene (20.22%) being identified as major constituents. The minimum inhibitory concentration (MIC) of EOPT was determined to assess its antibacterial activity against multidrug-resistant strains of Staphylococcus aureus (IS-58, 1199B, K2068, and K4100). The compound showed a MIC of ≥ 1024 µg/mL, suggesting a lack of intrinsic antibacterial activity. However, when the EOPT was associated with antibiotics and EtBr, a significant decrease in antibiotic resistance was observed, indicating the modulation of efflux pump activity. This evidence was corroborated with the observation of increased fluorescent light emission by the bacterial strains, indicating the involvement of the NorA and MepA efflux pumps. Additionally, the significant potentiation of ampicillin activity against the S. aureus strain K4414 suggests the ß-lactamase inhibitory activity of EOPT. These results suggest that the essential oil from P. tuberculatum fruits has antibiotic-enhancing properties, with a mechanism involving the inhibition of efflux pumps and ß-lactamase in MDR S. aureus strains. These findings provide new perspectives on the potential use of EOPT against antibiotic resistance and highlight the importance of Piper species as sources of bioactive compounds with promising therapeutic activities against MDR bacteria. Nevertheless, further preclinical (in vivo) studies remain necessary to confirm these in vitro-observed results.

Antibiotic-Potentiating Activity of the Schinus terebinthifolius Raddi Essential Oil against MDR Bacterial Strains.

Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus are the primary bacteria that cause clinical infections, such as urinary and intestinal infections, pneumonia, endocarditis, and sepsis. Bacterial resistance is an innate natural occurrence in microorganisms, resulting from mutations or the lateral exchange of genetic material. This serves as evidence for the association between drug consumption and pathogen resistance. Evidence has demonstrated that the association between conventional antibiotics and natural products is a promising pharmacological strategy to overcome resistance mechanisms. Considering the large body of research demonstrating the significant antimicrobial activities of Schinus terebinthifolius Raddi, the present study aimed to evaluate the chemical composition and antibiotic-enhancing effects of Schinus terebinthifolius Raddi essential oil (STEO) against the standard and multidrug-resistant strains of Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus. The STEO was extracted by hydrodistillation using a Clevenger-type vacuum rotary evaporator. The Minimum Inhibitory Concentration (MIC) of the STEO was assessed by the microdilution method to evaluate the antibacterial activity. The antibiotic-enhancing activity of the essential oil was assessed by determining the MIC of antibiotics in the presence of a sub-inhibitory concentration (MIC/8) of the natural product. The GC-MS analysis revealed alpha-pinene (24.3%), gamma-muurolene (16.6%), and myrcene (13.7%) as major constituents of the STEO. The STEO potentiated the enhanced antibacterial activity of norfloxacin and gentamicin against all the strains and increased the action of penicillin against the Gram-negative strains. Therefore, it is concluded that although the STEO does not exhibit clinically effective antibacterial activity, its association with conventional antibiotics results in enhanced antibiotic activity.

In vivo and in silico anti-inflammatory properties of the sesquiterpene valencene.

Valencene (VLN) is a sesquiterpene found in juices and essential oils of citrus species such as Cyperus rotundus. Considering the evidence that this species has anti-inflammatory effects, the present study aims to evaluate the anti-inflammatory activity of VLN in vivo and in silico. Swiss mice (n = 6) were orally treated according to their treatment groups as follows: VLN (10, 100 or 300 mg/kg), negative control (0.9% saline), and positive controls (indomethacin 25 mg/kg or promethazine 6 mg/kg). The anti-inflammatory activity was evaluated in murine models of acute and chronic inflammation. The inhibition of acute inflammation was evaluated in models of paw edema induced by different inflammatory agents (carrageenan, dextran, histamine, and arachidonic acid (AA)) and carrageenan-induced pleurisy and peritonitis. The modulation of chronic inflammation was evaluated in a granuloma model induced cotton pellets implantation. The interaction with inflammatory targets was evaluated in silico using molecular docking analysis. The administration of VLN to challenged mice significantly inhibited paw edema formation with no significant difference between the administered doses. The compound also reduced albumin extravasation, leukocyte recruitment, and the production of myeloperoxidase (MPO), IL-1ß, and TNF-α in both pleural and peritoneal lavages. According to the mathematical-statistical model observed in silico analysis, this compound has favorable energy to interact with the cyclooxygenase enzyme (COX-2) and the histamine 1 (H1) receptor. Finally, animals treated with the sesquiterpene showed a reduction in both granuloma weight and concentration of total proteins in a chronic inflammation model. Given these findings, it is concluded that NLV presents promising pharmacological activity in murine models of acute and chronic inflammation.

Comparative analysis of chemical profiles and antioxidant activities of essential oils obtained from species of Lippia L. by chemometrics.

Due to the importance of diseases associated with oxidative stress, the search for natural antioxidants proves to be essential. This work aimed to compare the chemical composition and antioxidant potential of essential oils from the genus Lippia L. through chemometric analysis. The essential oils were characterized by gas chromatography coupled with mass spectrometry. Antioxidant potentials were determined by DPPH, ABTS, Deoxyribose and ß-carotene protection, Iron chelation and reduction methods. All data were related by multivariate analyzes. Essential oils showed low similar chemical compositions and no statistically significant relationship. These showed relevant antioxidant activity, especially for L. sidoides that obtained IC50 of 5.22 ± 0.08 µg/mL in ABTS capture. Multivariate analyzes showed the effectiveness of L. alba compounds to DPPH scavenging, Fe3+ reduction and ß-carotene protection, and L. gracilis components to deoxyribose protect. Thus, studies proving the antioxidant potential of Lippia compounds against oxidative stress and their use in food conservation are fundamental.

Enhancement of the antibiotic activity mediated by the essential oil of Ocotea odorifera (VELL) ROWHER and safrole association.

In a recent study, our research group demonstrated that the essential oil of Ocotea odorifera (EOOO) and its major compound safrole potentiated the action fluoroquinolones, modulating bacterial resistance possibly due to direct inhibition of efflux pumps. Thus, in the present study, we investigated whether these treatments could enhance the activity of gentamicin and erythromycin against multidrug-resistant (MDR) bacteria. The EOOO was extracted by hydrodistillation, and the phytochemical analysis was performed by gas chromatography coupled to mass spectrometry (GC-MS). The antibiotic-enhancing effect of the EOOO and safrole against MDR strains of Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa was analyzed by the broth microdilution method. The chemical analysis confirmed the presence of safrole as a major component among the 16 compounds identified in the EOOO. Both the essential oil and the isolated compound showed clinically relevant antibacterial activities against S. aureus. Regarding the modulation of antibiotic resistance, the EOOO was found to enhance the activity of erythromycin against the strains of P. aeruginosa and S. aureus, as well as improving the action of gentamicin against S. aureus. On the other hand, safrole potentiated the activity of gentamicin against the S. aureus strain alone. It is concluded, therefore, that the EOOO and safrole can enhance the activity of macrolides and aminoglycosides, and as such are useful in the development of therapeutic tools to combat bacterial resistance against these classes of antibiotics.

Antioxidant Activity of Stryphnodendron rotundifolium Mart. Stem Bark Fraction in an Iron Overload Model.

Stryphnodendron rotundifolium Mart., popularly known as "barbatimão", is a plant species traditionally used by topical and oral routes for the treatment of infectious and inflammatory diseases. Considering the well-described antioxidant properties of this species, this study investigated the protective effects of its keto-aqueous extract using an in vitro model of iron overload. Phenolic compounds were quantified and identified by Ultra-Performance Liquid Chromatography coupled with quadrupole Time-Of-Flight Electrospray Ionization Mass Spectrometry (UPLC-ESI-qTOF-MS/MS) in positive and negative ions mode analysis. Antioxidant activity was analyzed following the iron-chelating-reducing capacity and deoxyribose degradation (2-DR) protection methods. The analysis identified condensed tannins (54.8 mg catechin/g dry fraction (DF), polyphenols (25 mg gallic acid/g DF), and hydrolyzable tannins (28.8 mg tannic acid/g DF). Among the constituents, prodelphinidin, procyanidin, and prorobinetinidine were isolated and identified. The extract significantly protected 2-DR degradation induced by Fe2+ (72% protection) or •OH (43% protection). The ortho-phenanthroline test revealed Fe2+-chelating and Fe3+-reducing activities of 93% and 84%, respectively. A preliminary toxicological analysis using Artemia salina revealed mortality below 10%, at a concentration of 0.25 mg/mL, indicating low toxicity under the present experimental conditions. In conclusion, the findings of the present study indicate that Stryphnodendron rotundifolium is a source of antioxidant compounds with the potential to be used in drug development in the context of iron overload disorders, which remains to be further investigated in vivo.

An evaluation of ticagrelor for the treatment of sickle cell anemia.

INTRODUCTION: Ticagrelor is an antiplatelet agent approved for the treatment of patients with an acute coronary syndrome or a history of myocardial infarction. Considering the evidence demonstrating that ticagrelor-mediated inhibition of platelet activation and aggregation have beneficial effects in the treatment of thrombotic conditions, clinical studies have been conducted to evaluate the use of this drug for the treatment of sickle cell disease (SCD), demonstrating satisfactory tolerability and safety. AREAS COVERED: Clinical investigation has characterized the pharmacokinetic and pharmacodynamical profile, as well as the efficacy and safety of ticagrelor to prevent painful vaso-occlusive crisis (painful episodes and acute chest syndrome) in SCD patients. EXPERT OPINION: While phase 1 and 2 clinical trials demonstrated satisfactory tolerability and safety, the conclusion of phase 3 clinical trials is crucial to prove the efficacy of ticagrelor as a therapeutic option for the treatment of SCD. Thus, it is expected that ticagrelor, especially in combination with other drugs, will improve the clinical profile and quality of life of patients with SCD.

Modulation of antibiotic resistance by the essential oil of Ocimum gratissimum L. in association with light-emitting diodes (LED) lights.

This study aimed to evaluate the antibacterial and antibiotic-enhancing effects of the essential oil obtained from Ocimum gratissimum L. (OEOg) alone or in association with light-emitting diodes (LED) lights. The essential oil was obtained by hydrodistillation and its chemical composition analysed by gas chromatography coupled to mass spectrometry. The antibacterial and antibiotic-enhancing activities against multiresistant strains of Staphylococcus aureus and Escherichia coli were evaluated by the gaseous contact method. The analysis of the photoinductive effect on the antibacterial activity of the OEOg and antibiotics was assessed through exposure to different LED lights (red, blue and yellow). The phytochemical analysis identified five compounds, including eugenol, as the major constituent. The OEOg caused a significant inhibition of the halo, indicating a direct antibacterial effect. Exposure to the LED lights significantly enhanced the activity of the OEOg against E. coli. On the other hand, the action of the essential oil against S. aureus was enhanced by exposure to both blue and yellow lights. The effects of LED light exposure on the activity of conventional antibiotics varied significantly according to the drug and the bacterial strain. However, most combinations of LED lights and the OEOg presented synergistic effects against resistant bacterial strains, indicating enhanced antibacterial activity. Thus, these in vitro findings suggest that both OEOg and LED lights have promising antibacterial effects. Nevertheless, further research is required to evaluate in vivo the potential of these therapies for the treatment of infectious skin diseases.

Anti-Inflammatory and Physicochemical Characterization of the Croton Rhamnifolioides Essential Oil Inclusion Complex in ß-Cyclodextrin.

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 ß-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 ß-cyclodextrin/Essential oil (ß-CD/EO) may present an important tool in the study of new compounds for the development of anti-inflammatory drugs.

Nootkatone Inhibits Acute and Chronic Inflammatory Responses in Mice.

Nootkatone (NTK) is a sesquiterpenoid found in essential oils of many species of Citrus (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-ß, 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 (H1). 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-ß 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.

Characterization and antibacterial activity of the essential oil obtained from the leaves of Baccharis coridifolia DC against multiresistant strains.

Essential oils are secondary metabolites with immense pharmacological potential.These substances are abundantly produced by plants of the family Asteraceae, such as Baccharis coridifolia. Previous studies have demonstrated that this species has pharmacological properties that make it a promising source of new antibacterial agents. Therefore, the present study aimed to evaluate the antibacterial and antibiotic-modulating activity of Baccharis coridifolia essential oil against multidrug-resistant (MDR) strains. The phytochemical analysis was carried out by gas chromatography coupled to Mass Spectroscopy (GC/MS), and realized the Minimum Inhibitory Concentation (MIC) and antibiotic-modulation from the microdilution method in 96-well plates. It was revealed the presence of germacrene D (23.7%), bicyclogermacrene (17.1%), and (E)-caryophyllene (8.4%) as major components. The minimum inhibitory concentration of essential oil against strains of Pseudomonas aeruginosa (512 µg/mL) and Staphylococcus aureus (128 µg/mL) demonstrated clinically relevant antibacterial activity. In addition, the combination of subinhibitory doses of the oil with conventional antibiotics showed synergism, indicating potentiation of the antibacterial effect. In conclusion, the essential oil of Baccharis coridifolia (EOBc) presented antibacterial and antibiotic-modulating activities that place this species as a source of molecules useful in the fight against bacterial resistance.

Influence of seasonal variation on phenolic content and in vitro antioxidant activity of Secondatia floribunda A. DC. (Apocynaceae).

This study reports the effects of seasonal variation on the total polyphenol and flavonoid content and the in vitro antioxidant activity of Secondatia floribunda A. DC. The extracts were prepared from the inner bark and heartwood of samples harvested in the 2015 to 2016. The total phenolic and flavonoid content was determined by specific qualitative tests. The in vitro antioxidant capacity was analyzed using the following tests: 1-1-diphenyl-2-picrylhydrazyl radical (DPPH), 2,2'-azinobis-3-ethylbenzenothiazoline-6-sulfonic acid (ABTS+), ferric reducing antioxidant power (FRAP) and iron (Fe2+) chelating activity. The total polyphenol and total flavonoid content varied over the harvest period. The DPPH and ABTS tests revealed that in the dry season had the most potent in vitro antioxidant activity, although the extracts obtained during the rainy season presented the higher Fe2+ chelating and Ferric reducing activities. In conclusion, the phenolic content and in vitro antioxidant activity are correlated, and both are influenced by seasonality.

Essential Oil of Croton ceanothifolius Baill. Potentiates the Effect of Antibiotics against Multiresistant Bacteria.

This study is a pioneer in reporting the antibacterial properties of the species Croton ceanothifolius Baill. The genus Croton belongs to the family Euphorbiaceae composed of numerous species with documented biological activities. However, the pharmacological properties of C. ceanothifolius remain poorly understood. The leaves of this plant were submitted to hydrodistillation for essential oil (CcEO) extraction and the phytochemical characterization of the oil was performed by GC/MS. The minimum inhibitory concentration of the CcEO was determined for the evaluation of antibacterial activity against multiresistant strains of Staphylococcus aureus, Pseudomonas aeruginosa, and Escherichia coli. The antibiotic-modulating activity of the oil, in combination with antibiotics, was also evaluated. The combination of the CcEO with penicillin, norfloxacin, and gentamicin presented a synergistic effect. This effect was more significant for the association with antibiotics of the quinolone and aminoglycoside classes against Escherichia coli. The association of oil with gentamicin showed better results with regard to the Gram-positive strain. The association of the oil with norfloxacin against P. aeruginosa also showed synergism, but the association with penicillin did not change the effect of this antibiotic. Thus, it is concluded that C. ceanothifolius essential oil selectively potentiates the action of antibiotics against multiresistant strains.

GC-MS-FID characterization and antibacterial activity of the Mikania cordifolia essential oil and limonene against MDR strains.

The present study evaluated the effect of the essential oil of Mikania cordifolia (EOMc) and its major constituent limonene alone or associated with antibacterial drugs against Multidrug Resistant Bacteria (MDR). To evaluate the antibacterial activity, the minimum inhibitory concentrations (MIC) of the oil and limonene against Pseudomonas aeruginosa, Escherichia coli and Staphylococcus aureus were determined. The antibiotic-modulating activity was assessed using subinhibitory concentrations (MIC/8) of these substances in combination with conventional antibacterial drugs. Although no relevant antibacterial activity of the natural products was detected, both substances modulated the action of antibiotics against resistant bacteria. The EOMc demonstrated the best modulating effect against P. aeruginosa, presenting synergistic effects when associated with gentamicin and norfloxacin. In addition, the oil reduced the MIC of norfloxacin against E. coli as well as reduced the MIC of gentamicin against S. aureus. On the other hand, the best effect of limonene was obtained against S. aureus. Thus, it is concluded that the essential oil Mikania cordifolia and the isolated compound limonene do not have clinically significant antibacterial effect, but modulate the action of antibiotics against MDR bacteria.

Curine Inhibits Macrophage Activation and Neutrophil Recruitment in a Mouse Model of Lipopolysaccharide-Induced Inflammation.

Curine is a bisbenzylisoquinoline alkaloid (BBA) with anti-allergic, analgesic, and anti-inflammatory properties. Previous studies have demonstrated that this alkaloid is orally active at non-toxic doses. However, the mechanisms underlying its anti-inflammatory effects remain to be elucidated. This work aimed to investigate the effects of curine on macrophage activation and neutrophil recruitment. Using a murine model of lipopolysaccharide (LPS)-induced pleurisy, we demonstrated that curine significantly inhibited the recruitment of neutrophils in association with the inhibition of cytokines tumor necrosis factor (TNF-α), interleukin (IL)-1ß, IL-6, monocyte chemotactic protein (CCL2/MCP-1) as well as leukotriene B4 in the pleural lavage of mice. Curine treatment reduced cytokine levels and the expression of iNOS in in vitro cultures of macrophages stimulated with LPS. Treatment with a calcium channel blocker resulted in comparable inhibition of TNF-α and IL-1ß production, as well as iNOS expression by macrophages, suggesting that the anti-inflammatory effects of curine may be related to the inhibition of calcium-dependent mechanisms involved in macrophage activation. In conclusion, curine presented anti-inflammatory effects that are associated with inhibition of macrophage activation and neutrophil recruitment by inhibiting the production of inflammatory cytokines, LTB4 and nitric oxide (NO), and possibly by negatively modulating Ca2+ influx.