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Background: Inflammation makes up a set of vascularized tissue reactions acting in the defense of the body against harmful stimuli. Natural products are a lower cost alternative with better benefit, often used in popular medicine in the treatment of inflammatory processes. Several species from the genus Croton have scientifically proven anti-inflammatory action., Purpose: This study aims to analyze the chemical composition of the Croton campestris A. St.-Hil essential oil (EOCC), derived from fresh leaves, as well as to evaluate the anti-inflammatory potential and the possible mechanisms of action of the EOCC and its constituent β-caryophyllene., Methods: The assays were performed in in vivo models of acute and chronic inflammation. Initially, the chemical composition of the EOCC was determined and its oral toxicity was evaluated, followed by the evaluation of its topical antiedematogenic effect through acute and chronic ear edema induced by Croton oil. For the systemic verification of an anti-inflammatory action, the abdominal contortions, formalin test, paw edema induced by carrageenan, dextran, histamine and arachidonic acid models, as well as a peritonitis test, vascular permeability and granuloma assays were performed., Results: The evaluation of the essential oil chemical composition revealed the presence of β-caryophyllene (15.91%), 1,8-cineol (16.98%) and germacrene-D (14.51%) as its main constituents. The EOCC had no relevant clinical toxicity on oral administration, with an LD 50 of more than 5000 mg/kg. The tested substances showed anti-inflammatory action in the abdominal contortions, paw edema induced by carrageenan, dextran, histamine and arachidonic acid models, the formalin test, peritonitis test and vascular permeability; however, β-caryophyllene had no significant effect on the granuloma assay. This suggests as a hypothesis that both substances tested showed significant influence on the arachidonic acid and histamine pathway reducing edema in these models., Conclusion: The tested substances have a clinically safe profile, additionally the EOCC and β-caryophyllene presented relevant anti-inflammatory activity. This study supports the hypothesis that β-caryophyllene, in association with other constituents present in the EOCC such as 1,8-cineole, contributed to the anti-inflammatory effect observed, in addition to suggesting that one of the mechanisms of action probably involves the inhibition of cytokines with the involvement of the arachidonic acid and histamine pathways., (Copyright © 2018 Elsevier GmbH. All rights reserved.)

The aim of this study was to identify the presence of tannins, phenols and flavonoids on the hydroalcoholic extract of Caryocar coriaceum leaves (HECCL) and to determine the antioxidant and antibacterial activity of this extract. The extract was tested alone (1024-1 μg/mL) or associated (MIC/8) with several antibiotics in order to identify any antibacterial activity against multiresistant bacterial strains (Escherichia coli, Staphylococcus aureus and Pseudomonas aeruginosa). The existence of tannins, total phenols (901.31 mg/g) and flavonoids (89.68 mg/g) was confirmed in the HECCL. The presence of rutin and quercetin were confirmed by Thin-layer chromatography (TLC). Using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) method, the antioxidant activity of the extract (9 μg/mL) was determined. Moreover, the Minimum Inhibitory Concentration (MIC) value found for HECCL was 1024 μg/mL and the association between HECCL (MIC/8) with benzylpenicillin significantly changed its minimum inhibitory concentration from 2500 to 625 μg/mL against E. coli.

Tocoyena formosa, a small ornamental tree growing in the dry regions of central Brazil, is commonly known as 'genipapo do bravo'. This is a medicinal plant traditionally used as an analgesic for rheumatic pain, lower back pain and myalgia, however its use is carried out without scientific evidence, which thus justifies the development of studies to investigate and prove its therapeutic potential. Therefore, the objective of this study was to evaluate the phytochemical profile of Tocoyena formosa (Cham. & Schlecht.) K. Schum (TFLHE) and the mechanisms involved in its anti-nociceptive effect. The TFLHE revealed the presence of gallic acid, catechin, chlorogenic acid, caffeic acid, ellagic acid, rutin, quercetin and luteolin. The TFLHE at doses of 200 and 400mg/kg significantly decreased acetic acid-induced abdominal contortions, the reaction time for the formalin test in both phases and increased the paw withdrawal time in the hot plate thermal stimulus test. The 200mg/kg dose also significantly inhibited the plantar mechanical hyperalgesia intensity induced by formalin within 24h., Treatment: with the TFLHE did not cause significant changes in motor performance and coordination in the Rota Rod test. The investigation on the possible mechanism of antinociceptive action of TFLHE indicates the involvement of opioid, glutamatergic, nitric oxide/cGMP and vanilloid systems. It is concluded that the TFLHE has an antinociceptive effect promoted by the aforementioned mechanisms., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

The development of new drugs from plants is an interesting alternative approach to overcoming microbial resistance. Passiflora cincinnata shows resistance to diseases and pests and a higher concentration of chemical components that may be useful in the pharmaceutical industry. We investigated the potential antimicrobial and antibiotic-modifying activity of hydroalcoholic extracts of leaves, stems, bark, pulp and seeds of P. cincinnata . The extracts were prepared by homogenization of material in 50% ethanol. Minimum inhibitory concentration (MIC) was determined by the broth dilution method, and the bacterial strains tested were Staphylococcus aureus and Escherichia coli . Antibiotic-modifying activity was evaluated against the strains S. aureus 03 and E. coli 08, using a subinhibitory concentration of extract. The antibiotics tested were: amikacin, gentamicin, ampicillin, potassium benzylpenicillin and oxacillin. The extracts did not show antimicrobial activity of clinical relevance, where the MIC was equal to or greater than 1024 μg/mL. S. aureus showed 13 events, while E. coli showed only 4 events. Among these events, 14 involved synergistic activity, potentiating the effect of the antibiotics, and only 3 events demonstrated antagonistic activity toward ampicillin. Hydroalcoholic extracts are potential antimicrobial agents when combined with conventional drugs little utilized in in vivo treatment.

The Lippia alba (Mill.) N.E. Brown (Verbenaceae) species, has effects sedative, analgesic and spasmolytic properties. This study had as its main objective to evaluate the essential oil of L. alba (EOLa) effect and that of its main constituents, citral and limonene, over tracheal smooth muscle from Wistar rats. EOLa, citral and limonene promoted relaxation of tracheal smooth muscle in contractions induced by potassium (60 mM K + ), presenting an EC 50 of 148 ± 7 μg/mL for the EOLa, 136 ± 7 μg/mL for citral and 581 ± 7 μg/mL for limonene. In contractions induced by Acetylcholine (Ach; 10 μM) the EC 50 for the EOLa and citral were of 731 ± 5 μg/mL and 795 ± 9 μg/mL, respectively. In preparations pre-incubated with 1000 μg/mL of the EOLa and citral, both agents were found to block the influx of BaCl 2 by VOCCs. This study demonstrated that the EOLa and its main component citral present antispasmodic effect over tracheal smooth muscle of rats.

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., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

The use of natural products is crucial to suppress the development of these micro-organisms and to reduce the concentration necessary to inhibit these microrganisms, reducing the toxicity risks also. In this study, the essential oil from Chenopodium ambrosioides Leaves and its main constituent α-Terpinene were used in the antibacterial and potentiating activity of antibiotics and ethidium bromide assays, against the bacterial strains Staphylococcus aureus IS-58, carriers of efflux pumps. The Minimum Inhibitory Concentration (MIC) was determined using a microdilution method. The capacity of the aforementioned was also tested in combination with tetracycline and ethidium bromide, with the aim of improving the activity of the antibacterials. The MIC of the C. ambrosioides L. essential oil and of α-Terpinene were above 1024 μg/mL, comprising a clinically irrelevant value. However, when associated with the antibiotics, the C. ambrosioides L. essential oil, significantly decreased the MIC of tetracycline and ethidium bromide. The efflux pump is the only mechanism the bacteria possesses to reduce the toxicity of ethidium bromide, and thus this reduction in the MIC demonstrates that the C. ambrosioides L. essential oil is an effective option in the inhibition of the efflux pump present in these micro-organisms., (Copyright © 2017. Published by Elsevier Ltd.)

Orange jasmine, Murraya paniculata (Rutaceae), is a plant from India widely used in folk medicine as antinociceptive, antiinflammatory, and antioxidant. Although oral hypoglycemic agents and insulin are the mainstays of treatment of diabetes mellitus (DM), there is a significant demand for new natural products to reduce the development of diabetic complications. Alloxan-induced diabetic rats were treated for 60 days with a hydroalcoholic extract of M. paniculata (MPE), at doses of 100, 200, and 400 mg/kg. MPE decreased glycemia and also cholesterol and triglyceride levels, starting 1 week after treatments, as compared with the same group before treatments. Glucose values were reduced toward normality after 1 week of treatment. MPE hypoglycemic effects were potentiated by glibenclamide and metformin. MPE also decreased fructosamine and glycated hemoglobin values. MPE reduced diabetes-induced morphological alterations of the kidney, pancreas, and liver. MPE acts similarly to glibenclamide and metformin, and its glucose-lowering action is partly a consequence of ATP-sensitive K + channel inhibition. MPE may be a potential therapeutic alternative for the treatment of diabetes and its complications. Copyright © 2017 John Wiley & Sons, Ltd., (Copyright © 2017 John Wiley & Sons, Ltd.)

Cyclodextrins (CDs) are cyclic oligosaccharides can enhance the bioavailability of drugs. Ocimum basilicum is an aromatic plant found in Brazil used in culinary. The essential oil of this plant presents anti-edematogenic and anti-inflammatory activities in acute and chronic inflammation. The aim of this study was to investigate the anti-inflammatory effects of the essential oil obtained from O. basilicum complexed with β - cyclodextrin (OBEO/β-CD) in mice. The complexation with β-cyclodextrin (β-CD) was performed by different methods and analyzed by differential scanning calorimetry (DSC), thermogravimetry (TG) and scanning electron microscopy (SEM). The anti-inflammatory activity was evaluated using mice models of paw edema induced by carrageenan, dextran, histamine and arachidonic acid (AA); vascular permeability and peritonitis induced by carrageenan and granuloma induced by cotton block introduction. The DSC, TG and SEM analysis indicated that the OBEO was successfully complexed with β-CD. The oral administration of OEOB/β-CD prevented paw edema formation by decreasing vascular permeability in vivo, inhibited leukocyte recruitment to the peritoneal cavity, and inhibited granuloma formation in mice. Our results indicate that conjugation with β-CD improves the anti-inflammatory effects of OBEO in mice models of acute and chronic inflammation, indicating that this complex can be used in anti-inflammatory drug development., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

The widespread use of antibiotics created selective pressure for the emergence of strains that would persist despite antibiotic toxicity. The bacterial resistance mechanisms are several, with efflux pumps being one of the main ones. These pumps are membrane proteins with the function of removing antibiotics from the cell cytoplasm. Due to this importance, the aim of this work was to evaluate the inhibitory effect of tannic acid against efflux pumps expressed by the Staphylococcus aureus RN4220 and IS-58 strains. The efflux pump inhibition was assayed using a sub-inhibitory concentration of efflux pump standard inhibitors and tannic acid (MIC/8), observing their capacity to decrease the MIC of Ethidium bromide (EtBr) and antibiotics due the possible inhibitory effect of these substances. The MICs of EtBr and antibiotics were significantly different in the presence of tannic acid, indicating the inhibitory effect of this product against efflux pumps of both strains. These results indicate the possible usage of tannic acid asan inhibitor and an adjuvant in the antibiotic therapy against multidrug resistant bacteria (MDR)., (Copyright © 2017 Elsevier Inc. All rights reserved.)

The aim of this study was to investigate the effect of the dry and rainy season on the antibacterial activity and chemical composition of the Brazilian red propolis. The samples were collected in rainy (RP-PER) and dry (RP-PED) seasons and analyzed by HPLC-DAD. The extracts were tested alone and in association with antibiotics against Escherichia coli, Pseudomonas aeruginosa and Staphylococcus aureus. The HPLC analysis identified luteolin and quercetin as the main compounds. Seasonal variation was observed according to concentrations of the compounds. The MIC values against E. coli ranged from 128 μg/mL to 512 μg/mL (EC 06 and EC ATCC). The red propolis showed MIC values of 512 μg/mL against both strains of P. aeruginosa used in our study (PA03 and PA24) and against strains of Gram-positive bacteria S. aureus the MICs ranged from 64 μg/mL to ≥1024 μg/mL (SA10). A synergistic effect was observed when we combined the RP-PED with gentamicin against all the strains tested. When we combined the RP-PED with Imipenem, we only observed synergistic effect against P. aeruginosa. According to our synergistic activity results, the utilization of red propolis collected in the drier periods can be used as an adjuvant against multiresistant bacterial infections., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

The evaluation of the leishmanicidal and trypanocidal activity of the hydroalcoholic extract of the bark of Stryphnodendron rotundifolium Mart. (EHCSR) was carried out to find an alternative treatment for parasitic diseases. EHCSR was prepared and used at four different concentrations (1000, 500, 250, 125 μg/mL) in in vitro assays for activity against Leishmania promastigotes using the species Leishmania brasiliensis and Leishmania infantum and for trypanocidal activity using the epimastigotes of Trypanosoma cruzi . We also tested EHCSR for cytotoxicity against adhered cultured Murine J774 fibroblasts. The tests were performed in triplicate, and the percent mortality of parasites, IC 50 and percent toxicity were determined. With regard to anti-leishmania activity against L. infantum , there was a mean mortality of 45% at all concentrations, and against L. brasiliensis , a substantial effect was seen at 1000 μg/mL with 56.38% mortality, where the IC 50 values were 1338.76 and 987.35 μg/mL, respectively. Trypanocidal activity was notably high at 1000 μg/mL extract with 82.31% mortality of epimastigotes. Cytotoxicity at the highest extract concentrations of 500 and 1000 μg/mL was respectively 75.12% and 94.14%, with IC 50  = 190.24 μg/mL. Despite that the extract has anti-parasitic activity, its substantial cytotoxicity against fibroblasts cells makes its systemic use nonviable as a therapeutic alternative.

Chronic musculoskeletal pain is one of the main symptoms found in Fibromyalgia with unclear etiology and limited pharmacological treatment. The aim of this study was to complex LIM in β-cyclodextrin (LIM-βCD) and then evaluate its antihyperalgesic effect in an animal model of chronic musculoskeletal pain. Differential scanning calorimetry and scanning electron microscopy was used for the characterization of the inclusion complex. Male Swiss mice were used for experimental procedures where mechanical hyperalgesia, thermal hyperalgesia, muscular strength, Fos immunofluorescence was studied after induction of hyperalgesia. Mechanism of action was also investigated through tail flick test and capsaicin-induced nociception. Endothermic events and morphological changes showed that the slurry complex method was the best method for the complexation. After induction of hyperalgesia, the oral administration of LIM-βCD (50mg/kg) significantly increased the paw withdrawal threshold compared to uncomplexed limonene. Fos immunofluorescence showed that both compounds significantly decreased the number of Fos-positive cells in the dorsal horn. In nociceptive tests, FLU was able to reverse the antinociceptive effect of LIM-βCD. After intraplantar administration of capsaicin, LIM was able to significantly decrease time to lick. LIM-βCD has antihyperalgesic action superior to its uncomplexed form, with possible action in the dorsal horn of the spinal cord. These results suggest the possible applicability of LIM, uncomplexed or complexed with βCD, in conditions such as FM and neuropathic pain, for which there are currently only limited pharmacological options., (Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.)

Objectives: Epilepsy is a common brain disease and a major worldwide public health problem. The seizures in a significant number of patients suffering from epilepsy remain inadequately controlled by currently available pharmacological treatments. Accordingly, there is a need for the discovery of new anticonvulsant approaches with improved efficacy and a better safety profile. In this context, natural products can be a valuable source of substances with potential anticonvulsant activity. In the present study, we tested the anticonvulsant potential of Caryocar coriaceum Wittm., a plant native from the Brazilian Cerrado biome (tropical savanna ecoregion)., Methods: Adult male C57BL/6 mice were treated with increasing doses of the fixed oil obtained from the pulp of Caryocar coriaceum Wittm. Seizure activity was induced by PTZ (60 mg/kg, i.p.), and evaluated by behavioral and electrographic methods. Potential adverse effects were investigated in the open-field, rotarod, forced swim, or object recognition tests. The antioxidant potential of the oil was evaluated by the DPPH scavenging assay., Results: Administration of the oil at the dose of 100 mg/kg increased the latency for the first myoclonic jerk and the first generalized tonic-clonic seizures. The duration of generalized convulsions induced by PTZ was not altered. No significant behavioral adverse effects were detected in the open-field, rotarod, forced swim, or object recognition tests. Interestingly, a significant antioxidant activity of Caryocar coriaceum Wittm. fixed pulp oil was detected in the DPPH scavenging assay., Discussion: Natural products can be a valuable source of substances with potential anticonvulsant activity and improved safety profile. Further studies are needed to evaluate the mechanisms underlying the anticonvulsant effects of Caryocar coriaceum Wittm. fixed pulp oil as well as the potential of the oil as a source of new anticonvulsant compounds.

The increase in microorganisms with resistance to medications has caused a strong preoccupation within the medical and scientific community. Animal toxins studies, such as parotoid glandular secretions from amphibians, possesses a great potential in the development of drugs, such as antimicrobials, as these possess bioactive compounds. It was evaluated Rhinella jimi (Stevaux, 2002) glandular secretions against standard and multi-resistant bacterial strains; the effect of secretions combined with drugs; and determined the toxicity using two biologic in vivo models, and a in vitro model with mice livers. Standard strains were used for the determination of the Minimum Inhibitory Concentration (MIC), while for the modulatory activity of antibiotics, the clinical isolates Escherichia coli 06, Pseudomonas aeruginosa 03 and Staphylococcus aureus 10 were used. Modulatory activity was evaluated by the broth microdilution method with aminoglycosides and β-lactams as target antibiotics. The secretions in association with the antibiotics have a significant reduction in MIC, both the aminoglycosides and β-lactams. The toxicity and cytotoxicity results were lower than the values used in the modulation. R. jimi glandular secretions demonstrated clinically relevant results regarding the modulation of the tested antimicrobials., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

The present study aimed to evaluate the antibacterial and modulatory potential of α-bisabolol, β-cyclodextrin and α-bisabolol/β-cyclodextrin complex. The minimum inhibitory concentration was determined through the broth microdilution technique using the bacterial strains: Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa. The drugs norfloxacin, imipenem and gentamicin were used in the tests, and the compounds α-bisabolol and β-cyclodextrin; all the compounds were diluted in DMSO. To obtain the minimum inhibitory concentration (MIC) a serial microdilution of the substances in volumes corresponding to the sub-inhibitory concentration (MIC/8), and microdilution with the antibiotic until the penultimate well were performed. The results showed that β-cyclodextrin did not present synergistic effects when combined with the antibiotics. It was found that α-bisabolol presented a synergistic effect against S. aureus, when combined with the antibiotic norfloxacin. Moreover, α-bisabolol presented synergism against E. coli when combined with gentamicin. The results of this study show that α-bisabolol presents a modulatory synergistic effect for some antibiotics, as gentamicin, and this is an interesting result against multidrug resistant bacteria (MDR). By other side, the complexation of α-bisabolol with β-cyclodextrin apparently reduces the modulatory effect, maybe due the polarity enhancement of the polarity of α-bisabolol, affecting the interaction of this compound with the cell membrane bilayer. However, more studies are necessary to demonstrate or not these interactions., (Copyright © 2017. Published by Elsevier Masson SAS.)

Background: Due to its unclear pathophysiology, the pharmacological treatment of fibromyalgia is a challenge for researchers. Studies using medicinal plants, such as those from the genus Lippia, complexed with cyclodextrins (CDs) have shown innovative results., Objective: The present research intended to evaluate the effect of an inclusion complex containing β-cyclodextrin (βCD) inclusion complex with Lippia grata (LG) essential oil in a chronic musculoskeletal pain model, its central activity and its possible interaction with neurotransmitters involved in pain., Methods: After acid saline-induced chronic muscle pain, male mice were evaluated for primary and secondary hyperalgesia and muscle strength. Moreover, an antagonist assay was performed to assess the possible involvement of the opioidergic, serotonergic and noradrenergic pathways. In addition, Fos protein in the spinal cord was assessed, and a docking study and antioxidant assays were performed., Results: The treatment with LG-βCD, especially in the dose of 24mg/kg, was able to significantly decrease (p<0.05) the paw withdrawal and muscle threshold. Furthermore, LG-βCD was shown to affect the opioidergic and serotonergic pathways. There were no significant changes in muscle strength. Fos protein immunofluorescence showed a significant decrease in expression in the dorsal horn of the spinal cord. The main compounds of LG showed through the docking study interaction energies with the alpha-adrenergic and μOpioid receptors. In all antioxidant assays, LG exhibited stronger antioxidant activities than LG-βCD., Conclusion: This study suggested that LG-βCD could be considered as a valuable source for designing new drugs in the treatment of chronic pain, especially musculoskeletal pain., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

The association of herbal products with standard antimicrobial drugs has recently gained more attention as a hope to overcome infectious diseases caused by multidrug-resistant microorganisms. Here, we investigated for the first time the antimicrobial (antifungal and antibacterial) activity of ethanolic and aqueous extracts of R. echinus against multiresistant strains of bacteria (E. coli, P. aeruginosa and S. aureus) and fungi (C. albicans, C. krusei and C. tropicalis), as well as potential to enhance the activity of antibiotics drugs. In addition, both extract were chemically characterized and their toxicity was assessed in Artemia salina. Our results demonstrate that aqueous extract of R. echinus caused a significant increase in the activity of antibiotics gentamicin and imipenem, while the ethanolic extract strongly enhanced the antibiotic activity of gentamicin, amikacin, imipenem and ciprofloxacin against P. aeruginosa. However, neither the ethanolic nor the aqueous extracts significantly affect the antibiotic activity of the drugs when tested against S. aureus. Phytochemical analysis of the extracts indicated ellagic acid, caffeic acid and chlorogenic acid as the major components which can be at least in part responsible for the enhanced activity of antibiotics. None of the extracts showed toxicity in A. salina even at the highest concentration tested (1000 μg/mL). All together, our results suggest that the leaf extract of R. echinus can be an effective source of modulating agents., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: Croton rhamnifolioides Pax is a plant species that have been used in the folk medicine to treat ulcers, inflammations and hypertension. However, despite the relevant data obtained from ethnopharmacological studies, the pharmacological properties endorsing the efficacy of this plant to treat ulcer remain to be elucidated., Hypothesis/purpose: The present study aimed to characterize the chemical profile and evaluate the gastroprotective activity of the essential oil obtained from C. rhamnifolioides Pax (OECC) in mice., Methods: The essential oil of Croton rhamnifolioides was obtained by hydrodistillation and analyzed by gas-phase chromatography coupled to mass spectrometry (GC/MS). The median lethal dose was determined employing an acute toxicity test. The gastroprotective activity of the OECC was investigated using animal models of gastric ulcer induced by the administration of absolute ethanol, acidified ethanol or indomethacin. Mechanisms of action were investigated using the physical barrier test and by in vivo evaluation of the involvement of the following molecular pathways: nitric oxide, ATP - dependent potassium channels, α 2 - noradrenergic receptors, capsaicin - sensitive afferent neurons and opioid receptor., Results: We identified the presence of 21 compounds in OECC, including spathulenol and 1,8 - cineole as major constituents. In orally administered mice, OECC caused no significant toxicity. OECC significantly prevented gastric lesions in all mice models. The barrier test demonstrated that the gastroprotective activity of OECC occurs in a systemic dimension. Our results demonstrated that the gastroprotective effect of OECC involves mechanisms that are related to modulation of opioid receptors and nitric oxide., Conclusion: In conclusion, OECC demonstrated significant gastroprotective activity associated with low toxicity, providing scientific evidences that C. rhamnifolioides have the potential for the development of new antiulcer drugs., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

Cyclodextrins (CDs) have been used as important pharmaceutical excipients for improve the physicochemical properties of the drugs of low solubility as the essential oil of Hyptis martiusii. This oil is important therapeutically, but the low solubility and bioavailability compromises your use. Therein, the aim of this study was to obtain and to characterize physico-chemically the samples obtained by physical mixture (PM), paste complexation (PC) and slurry complexation (SC) of the essential oil Hyptis martiusii (EOHM) in β-CD, and to compare the antibacterial and modulatory-antibiotic activity of products obtained and oil free. The physicochemical characterization was performed by differential scanning calorimetry (DSC), thermogravimetry/derivative thermogravimetry (TG/DTG), scanning electron microscopy (SEM), X-ray diffraction (XRD) and Karl Fischer titration. Additionally, the antibacterial tests were performed by microdilution technique. Thus, it was observed that the PM method showed low complexing capacity, unlike PC and SC in which it was observed the formation of inclusion complexes. In addition, the second stage of the TG/DTG curves showed that SC was the best method inclusion with mass loss of 6.9% over the PC that was 6.0%. The XRD results corroborate with the results above suggesting the formation of new solid phase and the SEM photomicrographs showed the porous surface of the samples PC and SC. The essential oil alone demonstrated an antibacterial and modulatory effect against the S. aureus and the Gram negative strain, respectively. However, the β-CD and the inclusion complex did not demonstrate any biological activity in the performed antibacterial assays., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

Objectives: Postgraduate programmes around the world are periodically subjected to research performance evaluation through bibliometric indicators. In this research, we characterized and compared the research performance of 15 universities from Northeastern Brazil, in which 13 were among the top Universities of the Latin America., Methods: Specifically, total documents, citations and the h-index of each university were retrieved from the Elsevier Scopus database and were analysed not only for historical scientific achievement but also across the period of the past 6 years (2010-2015). Using these bibliometric indicators, we also investigated the performance of programmes at these Universities that have their papers indexed in the Scopus database under the category of "Pharmacology, Toxicology and Pharmaceuticals" for the same period., Results: We found that the Federal University of Pernambuco (UFPE) and the Federal University of Ceará (UFC) were the most productive institutions, producing 17847 and 15048 documents, respectively. The number of papers published by each of these universities in the past six years represented more than 50% of their entire productivity. With regards to their scientific output in "Pharmacology, Toxicology and Pharmaceutics", UFC showed the highest number of published documents followed by UFPE and the Federal University of Paraíba (UFPB). UFC received the highest h-index (with and without self-citations) and number of citations and shared their most cited papers with foreign institutions from the USA and Germany. However, papers from UFC were published in journals with lower impact factors (2.322)., Conclusions: The present study shows where each of these universities stands and can be helpful in identifying potential collaborators in these areas of knowledge.

Lantana camara, the widely studied species, and L. montevidensis, the less studied species of the genus Lantana are both used in traditional medicine for the same purpose (anti-asthma, anti-ulcer, anti-tumor, etc). However, little is known about the toxicity of L. montevidensis and there is limited information on its chemical constituents. Here, we investigated for the first time the genotoxicity and cytotoxicity of the ethanolic (EtOH) and aqueous extracts from the leaves of Lantana montevidensis in human leukocytes, as well as their possible interaction with human erythrocyte membranes in vitro . The antioxidant activities of both extracts were also investigated in chemical and biological models. Treatment of leukocytes with EtOH or aqueous extracts (1-480 µg/mL) did not affect DNA damage index, but promoted cytotoxicity at higher concentrations (240-480 µg/mL). Both extracts did not modify the osmotic fragility of human erythrocytes. The extracts scavenged DPPH radical and prevented Fe 2+ -induced lipid peroxidation in rat's brain and liver homogenates, and this was likely not attributed to Fe (II) chelation. The HPLC analysis of the extracts showed different amounts of polyphenolic compounds (isoquercitrin, gallic acid, catechin, ellagic acid, apigenin, kaempferol, caffeic acid, rutin, quercitrin, quercetin, chlorogenic acid, luteolin) that may have contributed to these effects. These results supported information on the functional use of L. montevidensis in folk medicine.

Anacardium microcarpum Ducke (Anacardiaceae) is a native species of Brazil used in folk medicine for the treatment of several illnesses although its antioxidant activity has been reported in vitro , there is no evidence of this effect in an in vivo model. Here, we investigated the potential protective effect of hydroalcoholic extract (AMHE), methanol (AMMF) and acetate (AMAF) fraction of A. microcarpum against paraquat toxicity on survivorship, locomotor performance, antioxidant enzymes activity and reactive species using Drosophila melanogaster . Flies were exposed to the extract or fractions (1 and 10 mg/ml) in the presence or absence of paraquat (5 mM) in sucrose solution for 72 h. In addition, total phenolic content of extract and fractions was evaluated as well as ABTS radical scavenging capacity. Our results demonstrated that AMAF presented higher content of phenols and ABTS chelating potential. Treatment of flies with the extract or fractions did not alter the survivorship, locomotor ability, and acetylcholinesterase (AchE) activity per se. Paraquat caused 85 % mortality of flies and 30 % increase in reactive species generation, which were significantly attenuated by AMHE and AMMF. AAMF increased catalase activity (from 66.77 ± 6.64 to 223.94 ± 25.92 mU/mg of protein), while AMAF increased GST activity (from 477.76 ± 92 to 770.19 ± 147.92 mU/mg of protein) and catalase activity (from 66.77 ± 6.64 to 220.54 ± 26.63 mU/mg of protein). AMHE and AMMF were more effective in protecting against paraquat toxicity. Taken together, the data indicate the potential of this plant in acting as a protective and antioxidant agent in vivo .

Background: Anti-inflammatory drugs can be ineffective in treating some inflammatory conditions. Improved drug delivery systems like cyclodextrins (CDs) could enhance their efficacy and safety., Objective: We conducted a systematic review to evaluate the anti-inflammatory activity of compounds complexed in CDs, analyzing whether these complexes improved their pharmacological action., Methods: The search terms 'Anti-inflammatory Agents', 'Cyclodextrins' and 'Drug effects' were used to retrieve articles in SCOPUS, PUBMED, MEDLINE and EMBASE., Results: Forty-four papers were identified. In the in vivo and clinical studies, there was greater efficacy for complexed drugs when compared to control groups or uncomplexed drug, decreasing inflammation and inflammatory mediators. Through a meta-analysis, the preclinical studies demonstrated that the complexed drug had a significantly (p<0.001) greater anti-inflammatory effect than the non-CD-complexed drug., Conclusion: The use of CDs can improve the action of anti-inflammatory compounds and it can also be a way to reduce the side effects, therapeutic doses and toxicity., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

Orofacial pain is associated with diagnosis of chronic pain of head, face, mouth, neck and all the intraoral structures. Carvacrol, a naturally occurring isoprenoid with diverse class of biological activities including anti-inflammatory, analgesic, antitumor and antioxidant properties. Now, the antinociceptive effect was studied in mice pretreatment with carvacrol (CARV) and β-cyclodextrin complex containing carvacrol (CARV-βCD) in formalin-, capsaicin-, and glutamate- induced orofacial nociception. Mice were pretreated with vehicle (0.9% Nacl, p.o.), CARV (10 and 20mg/kg, p.o.), CARV-βCD (10 and 20mg/kg, p.o.) or MOR (10mg/kg, i.p.) before the nociceptive behavior induced by subcutaneous injections (s.c.) of formalin (20μl, 2%), capsaicin (20μl, 2.5μg) or glutamate (20μl, 25μM) into the upper lip respectively. The interference on motor coordination was determined using rotarod and grip strength meter apparatus. CARV-βCD reduced the nociceptive during the two phases of the formalin test, whereas CARV did not produced the reduction in face-rubbing behavior in the initial phase. CARV-βCD (20mg/kg, p.o.) produced 49.3% behavior pain while CARV alone at 20mg/kg, p.o, produced 28.7% of analgesic inhibition in the second phase of formalin test. CARV, CARV-βCD and Morphine (MOR) showed a significant reduction against nociception caused by capsaicin or glutamate injection. Thus the encapsulation of carvacrol in β-cyclodextrin can acts as a considerable therapeutic agent with pharmacological interest for the orofacial pain management., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

Ethnopharmacological Relevance: Stachys lavandulifolia Vahl (Lamiaceae) is a medicinal plant widely used in Turkey and Iranian folk medicine due to its analgesic and anti-inflammatory properties, but little is known about its essential oil., Aim of This Study: We studied the antinociceptive and anti-inflammatory effects of S. lavandulifolia essential oil (EOSl) and (-)-α-bisabolol (BIS), its main compound, in algogen-induced orofacial nociceptive behavior in mice, and assessed the possible involvement of pro-inflammatory cytokines in these profiles., Materials and Methods: The GC-FID and GC-MS analysis of EOSl demonstrated the presence of (-)-α-bisabolol (56.4%), bicyclogermacrene (5.3%), δ-cadinene (4.2%) and spathulenol (2.9%) as the main compounds. Male Swiss mice were pretreated with EOSl (25 or 50mg/kg, p.o.), BIS (25 or 50mg/kg, p.o.), morphine (3mg/kg, i.p.) or vehicle (saline 0.9% with two drops of tween 80, 0.2%), before formalin- (20μl, 2%), capsaicin- (20μl, 2.5µg) or glutamate- (20μl, 25Mm) injection into the right upper lip (perinasal area) in mice. The anti-inflammatory profile of EOSl or BIS (50mg/kg) was assessed by the inflammatory response induced by carrageenan (2% in 0.2mL) in mice (pleurisy model)., Results: Our results showed that p.o. treatment with EOSl and BIS displayed significant inhibitory (p<0.05 or p<0.01 or p<0.001) effects in different orofacial pain tests on mice, but BIS proved to be more effective, significantly reducing nociceptive behavior in all tests including both phases of the formalin test. The analgesic effect is not related to any abnormality since EOSl- or BIS-treated mice exhibited no performance alteration in grip strength. Moreover, EOS1 and BIS exhibited a significant anti-inflammatory effect (p<0.001) in the pleurisy model of inflammation, which seems to be related to a significant reduction (p<0.05) of the pro-inflammatory cytokine TNF-α in BIS treatment, and of the pro-inflammatory cytokine IL-1β (p<0.01) in EOS1 treatment., Conclusion: Our results corroborate the use of S. lavandulifolia in traditional medicine as an analgesic and anti-inflammatory, which seems to be related to (-)-α-Bisabolol, the main compound of EOSl., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Background: The use of natural resources for the treatment of acute respiratory infections in children is a widespread practice within traditional communities, especially by women by being the primary caregivers. This study aimed to perform ethnobiological survey of plants and animals used for the treatment of acute respiratory infections in children of a traditional community in the municipality of Barbalha, Ceará, Brazil., Methods: It is a descriptive exploratory study with a quantitative approach, developed in Sitio Santo Antonio, in the municipality of Barbalha, Ceará, Brazil. As a tool for data collection, was applied a questionnaire and a semi-structured interview. Data analysis used descriptive statistics (simple and percentage rate) and the Relative Frequency of Citation., Results: The research included a total of 54 informants. In total, there were 38 species cited. According to the Relative Frequency of Citation the following species were the most cited: Ocimum basilicum L. (0.59), Eucalyptus globulus Labili (0.59), Plectranthus amboinicus (L.) Spreng (0.42), Hyptis suaveolens (L.) Poit. (0.24), Allium aescalonicum L. (0.22) and Mentha arvensis L. (0.18). Among the symptoms mentioned by the research subjects to treat the acute respiratory infections in childhood, there were: fever; cough; coughing with secretions; sore throat; hoarseness; tiredness; nasal congestion., Conclusions: It is important the knowledge about the usefulness of natural resources as alternative practices in diseases treatment, seeking to rescue popular knowledge used in the traditional community and fomenting the need to consider cultural aspects in the full practice to children's health care.

The therapeutic combinations have been increasingly used against fungal resistance. Natural products have been evaluated in combination with pharmaceutical drugs in the search for new components able to work together in order to neutralize the multiple resistance mechanisms found in yeasts from the genus Candida. The aqueous and hydroethanolic extracts from Psidium brownianum Mart ex DC. and Psidium guajava L. species were evaluated for their potential to change the effect of commercial pharmaceutical drugs against Candida albicans and Candida tropicalis strains. The tests were performed according to the broth microdilution method. Plate readings were carried out by spectrophotometry, and the data generated the cell viability curve and IC50 of the extracts against the yeasts. A chemical analysis of all the extracts was performed for detection and characterization of the secondary metabolites. The total phenols were quantified in gallic acid eq/g of extract (GAE/g) and the phenolic composition of the extracts was determined by HPLC. Fluconazole and all extracts presented high Minimum Inhibitories Concentrations (MICs). However, when associated with the extracts at sub-inhibitory concentrations (MIC/16), fluconazole had its effect potentiated. A synergistic effect was observed in the combination of fluconazole with Psidium brownianum extracts against all Candida strains. However, for Psidium guajava extracts the synergistic effect was produced mainly against the Candida albicans LM77 and Candida tropicalis INCQS 400042 strains. The IC50 values of fluconazole ranged from 19.22 to 68.1 μg/mL when it was used alone, but from 2.2 to 45.4 μg/mL in the presence of the extracts. The qualitative chemical characterization demonstrated the presence of phenols, flavonoids and tannins among the secondary metabolites. The concentration of total phenols ranged from 49.25 to 80.77 GAE/g in the P. brownianum extracts and from 68.06 to 82.18 GAE/g in the P. guajava extracts. Our results indicated that both P. brownianum and P. guajava extracts are effective on potentiating the effect of fluconazole, and therefore, these plants have the potential for development of new effective drugs for treating fungal infections., (Copyright © 2016 Elsevier Ltd. All rights reserved.)