Pentylenetetrazole: a review.

Pentylenetetrazole (PTZ), a tetrazole derivative, is commonly used as a chemical agent to induce neurological disorders and replicate the characteristics of human epileptic seizures in animal models. This review offers a comprehensive analysis of the behavioral, neurophysiological, and neurochemical changes induced by PTZ. The epileptogenic and neurotoxic mechanisms of PTZ are associated with an imbalance between the GABAergic and glutamatergic systems. At doses exceeding 60 mg/kg, PTZ exerts its epileptic effects by non-competitively antagonizing GABAA receptors and activating NMDA receptors, resulting in an increased influx of cations such as Na+ and Ca2+. Additionally, PTZ promotes oxidative stress, microglial activation, and the synthesis of pro-inflammatory mediators, all of which are features characteristic of glutamatergic excitotoxicity. These mechanisms ultimately lead to epileptic seizures and neuronal cell death, which depend on the dosage and method of administration. The behavioral, electroencephalographic, and histological changes associated with PTZ further establish it as a valuable preclinical model for the study of epileptic seizures, owing to its simplicity, cost-effectiveness, and reproducibility.

Neuroprotective effect of cinnamic alcohol: A bioactive compound of Cinnamomum spp. essential oil.

Cinnamic alcohol (CA) is a phenylpropanoid found in the essential oil of the bark of the genus Cinnamomum spp. Schaeff. (Lauraceae Juss.), known as cinnamon. To evaluate the neuroprotective effect of CA and its possible mechanism of action on mice submitted to the pentylenetetrazole (PTZ) induced epileptic seizures model. Behavioral, neurochemical, histomorphometric and immunohistochemistry analysis were carried out. The administration of CA (50-200 mg/kg, i.p., 30 min prior to PTZ and 0.7-25 mg/kg, i.p., 60 min prior to PTZ) increased the latency to seizure onset and the latency to death. The effects observed with CA treatment at 60 min were partially reversed by pretreatment with flumazenil. Furthermore, neurochemical assays indicated that CA reduced the concentration of malondialdehyde and nitrite, while increasing the concentration of reduced glutathione. Finally, histomorphometric and immunohistochemistry analysis revealed a reduction in inflammation and an increase in neuronal preservation in the hippocampi of CA pre-treated mice. Taken together, the results suggest that CA seems to modulate the GABAA receptor, decrease oxidative stress, mitigate neuroinflammation, and reduce cell death processes.

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.

An In Silico Approach to Exploring the Antinociceptive Biological Activities of Linalool and its Metabolites.

Pain is characterized by the unpleasant sensory and emotional sensation associated with actual or potential tissue damage, whereas nociception refers to the mechanism by which noxious stimuli are transmitted from the periphery to the CNS. The main drugs used to treat pain are nonsteroidal anti-inflammatory drugs (NSAIDs) and opioid analgesics, which have side effects that limit their use. Therefore, in the search for new drugs with potential antinociceptive effects, essential oils have been studied, whose constituents (monoterpenes) are emerging as a new therapeutic possibility. Among them, linalool and its metabolites stand out. The present study aims to investigate the antinociceptive potential of linalool and its metabolites through a screening using an in silico approach. Molecular docking was used to evaluate possible interactions with important targets involved in antinociceptive activity, such as α2-adrenergic, GABAergic, muscarinic, opioid, adenosinergic, transient potential, and glutamatergic receptors. The compounds in the investigated series obtained negative energies for all enzymes, representing satisfactory interactions with the targets and highlighting the multi-target potential of the L4 metabolite. Linalool and its metabolites have a high likelihood of modulatory activity against the targets involved in nociception and are potential candidates for future drugs.

Investigation of mechanisms of action involved in the antidepressant-like effect of Trans,trans-farnesol in mice.

This study aimed to investigate, through in vivo and biochemical methodologies, the effect of trans,trans-farnesol (12.5, 25, 50 or 100 mg/kg, p.o.) acute administration, adopting different behavioral and neurochemical parameters associated with an acute induced-depression model in mice. The initial results showed that, the oral treatment with trans,trans-farnesol, at the dose of 100 mg/kg induced a possible antidepressant-like effect in animals subjected to forced swim test (FST) and reserpine-induced akinesia. In addition, it was observed that the compound in question has an effect size and properties similar to imipramine (prototype of tricyclic antidepressants), but devoid of proconvulsant adverse effect. In biochemical assays, the pretreatment with trans,trans-farnesol, at a dose of 100 mg/kg (p.o.), decreased the hippocampal concentration of thiobarbituric acid reactive substances (TBARS) and restored striatal levels of noradrenaline and serotonin in mice subjected to FST. Altogether, these results suggest that trans,trans-farnesol showed a significant antidepressant-like effect, which seems to be mediated by the antagonism of muscarinic cholinergic receptors, reduction of oxidative stress and the modulation of noradrenaline and serotonin content in the central nervous system.

Computational Studies Applied to Linalool and Citronellal Derivatives Against Alzheimer's and Parkinson's Disorders: A Review with Experimental Approach.

Alzheimer's and Parkinson's are neurodegenerative disorders that affect a great number of people around the world, seriously compromising the quality of life of individuals, due to motor and cognitive damage. In these diseases, pharmacological treatment is used only to alleviate symptoms. This emphasizes the need to discover alternative molecules for use in prevention. Using Molecular Docking, this review aimed to evaluate the anti-Alzheimer's and anti-Parkinson's activity of linalool and citronellal, as well as their derivatives. Before performing Molecular Docking simulations, the compounds' pharmacokinetic characteristics were evaluated. For Molecular Docking, 7 chemical compounds derived from citronellal, and 10 compounds derived from linalool, and molecular targets involved in Alzheimer's and Parkinson's pathophysiology were selected. According to the Lipinski rules, the compounds under study presented good oral absorption and bioavailability. For toxicity, some tissue irritability was observed. For Parkinson-related targets, the citronellal and linalool derived compounds revealed excellent energetic affinity for α-Synuclein, Adenosine Receptors, Monoamine Oxidase (MAO), and Dopamine D1 receptor proteins. For Alzheimer disease targets, only linalool and its derivatives presented promise against BACE enzyme activity. The compounds studied presented high probability of modulatory activity against the disease targets under study, and are potential candidates for future drugs.

Possible mechanisms involved in the neuroprotective effect of Trans,trans-farnesol on pilocarpine-induced seizures in mice.

This study aimed to investigate, through in vivo and in vitro methodologies, the effect of acute trans,trans-farnesol (12.5, 25, 50 or 100 mg/kg, p.o.) administration on behavioral and neurochemical parameters associated with pilocarpine-induced epileptic seizure (300 mg/kg, i.p.) in mice. The initial results showed that the compound in question presents no anxiolytic-like or myorelaxant effects, despite reducing locomotor activity in the animals at all doses tested. In addition, the lowest dose increased the latency to onset of the first epileptic seizure, and the time to death. In addition to decreasing the mortality percentage in mice submitted to the pilocarpine model. In this same model, pretreatment with the lowest dose of the compound decreased the hippocampal concentrations of thiobarbituric acid and nitrite, and partially restored striatal concentrations of noradrenaline, dopamine, and serotonin. Taken together, the results suggest that trans,trans-farnesol presents a central depressant effect which contributes to its antiepileptic action which, in turn, seems to be mediated by the antagonism of muscarinic cholinergic receptors, reduction of oxidative stress. and modulation of noradrenaline, dopamine and serotonin concentrations in the central nervous system.

The Protein-Rich Fraction from Spirulina platensis Exerts Neuroprotection in Hemiparkinsonian Rats by Decreasing Brain Inflammatory-Related Enzymes and Glial Fibrillary Acidic Protein Expressions.

Spirulina platensis is a cyanobacterium with high protein content and presenting neuroprotective effects. Now, we studied a protein-enriched fraction (SPF), on behavior, neurochemical and immunohistochemical (IHC) assays in hemiparkinsonian rats, distributed into the groups: SO (sham-operated), 6-hydroxydopamine (6-OHDA), and 6-OHDA (treated with SPF, 5 and 10 mg/kg, p.o., 15 days). Afterward, animals were subjected to behavioral tests and euthanized, and brain areas used for neurochemical and IHC assays. SPF partly reversed the changes in the apomorphine-induced rotations, open field and forced swim tests, and also the decrease in striatal dopamine and 3,4-dihydroxyphenylacetic acid contents seen in hemiparkinsonian rats. Furthermore, SPF reduced brain oxidative stress and increased striatal expressions of tyrosine hydroxylase and dopamine transporter and significantly reduced hippocampal inducible nitric oxide synthase, cyclooxygenase-2 and glial fibrillary acidic protein expressions. The data suggest that the protein fraction from S. platensis, through its brain anti-inflammatory and antioxidative actions, exerts neuroprotective effects that could benefit patients affected by neurodegenerative diseases, like Parkinson's disease.

Hypoglycemic, Hypolipidemic, and Anti-Inflammatory Effects of Beta-Pinene in Diabetic Rats.

Background: Diabetes is a metabolic disease linked to multiple comorbidities, such as low-grade inflammation. ß-pinene, a monoterpene commonly found in aromatic plants, is endowed with anti-inflammatory effect and this fact lead us to investigate the possible hypoglycemic, hypolipidemic and anti-inflammatory effects of the monoterpene in the alloxan-induced diabetes experimental model. Methods: Male Wistar rats (200-250 g) were treated orally with ß-pinene (25, 50, 100, and 200 mg/kg) or glibenclamide (5 mg/kg), for seven consecutive days. Diabetes was induced by alloxan (40 mg/kg) through the penile vein. On the seventh day of treatment, blood samples were collected for biochemical analysis. The anti-inflammatory effect of ß-pinene was evaluated using the carrageenan-induced paw edema model, followed by the carrageenan-induced peritonitis. Results: The treatment with ß-pinene decreased plasma glucose, triglyceride, VLDL, LDL, and HDL levels, when compared to those of the control group. In addition, the association ß-pinene 10 mg/kg + glibenclamide 2 mg/kg significantly decreased blood glucose, total cholesterol, and triglyceride level. Finally, oral treatment with ß-pinene reduced carrageenan-induced paw edema and leukocyte migration in the peritoneum. Taken together, our results indicate that ß-pinene shows hypoglycemic and hypolipemic effects, which may involve some common mechanisms of glibenclamide. Besides, the monoterpene presented an anti-inflammatory action in diabetic rats that needs further investigation in order to clarify such effect and its correlation with the alterations observed in plasma parameters of ß-pinene-treated diabetic rats.

Antinociceptive activity of the Psidium brownianum Mart ex DC. leaf essential oil in mice.

Chronic pain management has several adverse effects and research looking for new and effective pain management drugs posing lower undesirable effects is necessary. Given the above, the pharmacological investigation of medicinal plants significantly contributes to the dissemination of plant-derived therapeutics. The aim of this study was to evaluate the antinociceptive activity of the Psidium brownianum Mart ex DC. leaf essential oil (PBEO) and the participation of the opioid pathway in this effect in mice. Swiss Mus musculus male mice were tested using acute nociception models (acetic acid induced abdominal contortions, formalin, capsaicin and hot plate tests). The possible myorelaxant action of the PBEO was tested using the rotarod test. The essential oil reduced animal nociception in chemical and heat models, with this action being devoid of a myorelaxant effect. Naloxone (2 mg/kg, intraperitoneally - i.p.) partially antagonized the PBEO activity, possibly acting via opioid receptors. The results obtained provide evidence that the traditional Psidium brownianum use may be effective for pain treatment.

Anxiolytic and antidepressant-like effects of Annona coriacea (Mart.) and caffeic acid in mice.

This research evaluated the anxiolytic and antidepressant-like effects of a hydroethanolic extract from the leaves of Annona coriacea (EHFAC) and caffeic acid (CA). Mice were intraperitoneally treated with saline, EHFAC (1, 10, 20 mg/kg) or CA (0.15 mg/kg) and subject to the elevated plus-maze, open field, rota-rod, forced swimming and reserpine-induced akinesia tests. Pro-convulsant and anticholinergic effects were also evaluated. EHFAC presented anxiolytic-like effect on the elevated plus-maze, which was partially reversed by flumazenil. A similar effect was observed with CA. In the forced swimming test, EHFAC and CA reduced the immobility time of mice; such effect was potentiated when EHFAC or CA were associated with imipramine, bupropion and fluoxetine. The antidepressant-like effect was reinforced as EHFAC partially reversed the reserpine-induced akinesia. In addition, a pre-treatment with EHFAC and CA did not decrease the latency to 1st seizure of animals that received a sub-convulsive dose of PTZ, nor reduced the intensity of oxotremorine-induced tremors. Taken together, the results indicate that EHFAC and CA have anxiolytic and antidepressant-like effects, which involve important neurotransmitter systems, such as GABAergic and monoaminergic ones, being devoid of side effects, commonly associated with classical psychotropic drugs.

Effects of the Hyptis martiusii Benth. leaf essential oil and 1,8-cineole (eucalyptol) on the central nervous system of mice.

The aim of this study was to characterize the central effects of the Hyptis martiusii leaf essential oil (OEHM) and 1,8-cineole (eucalyptol) using behavioral animal models. Gas chromatography coupled to mass spectrometry (GC/MS) was used to characterize the chemical compounds present in the OEHM. For the behavioral tests, female Swiss mice treated with the OEHM (25, 50, 100 and 200 mg/kg, i.p.) and 1,8-cineole (50 mg/kg, i.p.) were used and subjected to the following tests: open field, elevated cross maze, rotarod, sodium pentobarbital- or ethyl ether-induced sleep time, pentylenetetrazol-induced convulsions, haloperidol-induced catalepsy, and ketamine-induced hyperkinesia. GC/MS analysis identified 20 constituents with the majority of them being monoterpenes and sesquiterpenes, with eucalyptol (1,8-cineol), the major sample compound (25.93%), standing out. The results showed the OEHM (25, 50 100 and 200 mg/kg, i.p.) and its major compound (50 mg/kg, i.p.) reduced animal motility in the open field test, increased pentobarbital- and ethyl ether-induced sleep time, as well as death latency in the pentylenetetrazole-induced convulsion model. However, the tested compounds were devoid of anxiolytic-like and myorelaxant activity. In addition, the OEHM (100 and 200 mg/kg, i.p.) and 1,8-cineole (50 mg/kg, i.p.) potentiated haloperidol-induced catalepsy and reduced ketamine-induced hyperkinesia. Taken together, the results suggest the OEHM has important hypnotic-sedative and antipsychotic-like effects, which appear to be due to the monoterpene 1,8-cineole, the major compound identified in the essential oil.

Anti-inflammatory activity of herb products from Licania rigida Benth.

PURPOSE: The objective of the present study was to evaluate the systemic anti-inflammatory activity of the hydroalcoholic extract of the leaves of Licania rigida Benth (EHFLR) on models of systemic inflammation in mice. METHODS: The quantitative chemical profiles of phenolic acids and flavonoids were performed by High-Performance Liquid Chromatography (HPLC). Systemic anti-inflammatory activity was determined from carrageenan and dextran-induced paw edema models and the animals were orally treated (p.o.) with EHFLR at doses of 25, 50, 100 mg/kg, indomethacin (10 mg/kg) for carrageenan-induced paw edema and promethazine (6 mg/kg) for dextran-induced paw edema. The possible mechanisms involved in the anti-inflammatory action of the extract were evaluated by the paw edema models induced by histamine and arachidonic acid, and by the model of carrageenan-induced peritonitis, where vascular permeability and leukocyte migration to the peritoneal cavity were evaluated. RESULTS: The results of the HPLC identified the presence of phenolic acids and flavonoids, with chlorogenic acid (1.16%) and Caempferol (0.81%) as the main constituents. From the results, it was concluded that the extract has an LD50 ≥5000 mg/kg when administered orally in mice as this dose did not trigger deaths in any of the observed groups. EHFLR (25 mg/kg) showed a significant antiderematogenic effect on histamine and arachidonic acid-induced paw edema at the third hour of the tests, with a percentage of inhibition of 46.64% and 18.33%, respectively. The extract (25 mg/kg, p.o.) also significantly reduced vascular permeability and leukocyte migration in the peritoneal cavity. CONCLUSIONS: It is concluded that EHFLR exerts a systemic anti-inflammatory action, which seems to depend, at least in part, on the inhibition of arachidonic acid metabolism and the action of vasoactive amines. In addition, the extract reduced the leukocyte migration in the peritoneal cavity, indicating that its action may be linked to the inhibition of pro-inflammatory cytokines.

Phytochemical Analysis and Central Effects of Annona Muricata Linnaeus: Possible Involvement of the Gabaergic and Monoaminergic Systems.

Annona muricata Linnaeus (Annonaceae), popularly known as graviola, is used in folk medicine as both sedative and anticonvulsant. This study correlates the neurochemical profile with the behavioral effects of the hydroalcoholic extract from the leaves of Annona muricata (HLEAM) in mice, proposing to elucidate their mechanism of action on the central nervous system. Flavonoids and phenolic compounds were identified and quantified by High Performance Liquid Chromatography (HPLC) method. The acute toxicity (median lethal dose - LD50) was determined by probitos method using the percentage of mortality based on the Hippocratic screen. HLEAM (25, 50 and 100 mg/kg) was tested, intraperitoneally (i.p.), in models of sedation, anxiety, motor coordination, and seizures. The endogenous levels of dopamine, norepinephrine and DOPAC were assayed by reverse-phase HPLC with electrochemical detection. The HPLC analysis of the extract revealed the presence of flavonoids (quercetin, isoquercitrin, quercitrin, rutin, and kaempferol) and phenolics acids (gallic, chlorogenic, ellagic and caffeic acids). The LD50 was 1091.7 mg/kg and Hippocratic screening indicated central nervous system depressant effect. HLEAM presented sedative effects at doses of 25, 50, and 100 mg/kg, as well as anxiolytic and anticonvulsant effects at a dose of 100 mg/kg. In addition, these effects were partially reversed by flumazenil. The monoamines analysis by HPLC showed that HLEAM decreased the level of norepinefrine and dopamine in the mouse brain striatum. Thus, the results indicate a possible interaction of HLEAM with the GABAergic and monoaminergic systems, adding medicinal value to the popular use of the plant for the treatment of behavioral and neurological disorders.

Antiparasitic Activity and Essential Oil Chemical Analysis of the Piper Tuberculatum Jacq Fruit.

With the increase of neglected diseases such as leishmaniasis and Chagas disease, there was a need for the search for new therapeutic alternatives that reduce the harm caused by medicine available for treatment. Thus, this study was performed to investigate the antiparasitic activity of the essential oil from the fruits of Piper tuberculatum Jacq, against lines of Leishmania braziliensis (MHOM/CO/88/UA301), Leishmania infantum (MHOM/ES/92/BCN83) and Trypanosoma cruzi (LC-B5 clone). Before running protocols, an analysis of the chemical composition of essential oil was conducted, which presented monoterpenes and sesquiterpenes. As major constituents, ß-pinene and α-pinene were identified. Regarding to antiparasitic activity, the essential oil had an EC50 values of 133.97 µg/mL and 143.59 µg/mL against variations promastigotes of L. infantum and L. braziliensis, respectively. As for trypanocidal activity, the oil showed EC50 value of 140.31 µg/mL against epimastigote form of T. cruzi. Moreover, it showed moderate cytotoxicity in fibroblasts with LC50 value of 204.71 µg/mL. The observed effect may be related to the presence of terpenes contained in the essential oil, since it has its antiparasitic activity proven in the literature.

Avaliação da atividade moduladora e citotóxica do óleo essencial das folhas de Hyptis martiusii Benth / Evaluación de la actividad moduladora y citotóxica del aceite esencial de las hojas de Hyptis martiusii Benth / Assessment of Modulatory and Cytotoxic Activity of the Essential Oil in Hyptis Martiusii Benth Leaves

Resumo Introdução: a espécie Hyptis martiusii Benth, comumente chamada de "cidrera del campo", têm múltiplas propriedades biológicas, como ser inseticida, antifúngica e anti-inflamatória. O objetivo deste estudo foi investigar a atividade moduladora do óleo essencial das folhas frescas de Hyptis martiusii em associação com diferentes antibióticos contra as bactérias Staphylococcus aureus, Escherichia coli e Pseudomonas aeruginosa, e avaliar a atividade citotóxica da espécie. Materiais e métodos: o estudo utilizou a concentração inibitória mínima (CIM) como uma forma de avaliar a modulação com uma inoculação de 100 microlitros de cada estirpe bacteriana. As provas de citotoxicidade se realizaram mediante cultivo in vitro de células do tecido conectivo de camundongo (fibroblastos de mamíferos). Resultados: a pesquisa demonstrou que o óleo essencial das folhas de Hyptis martiusii Benth (OEHM) apresenta sinergismo só em associação com os antibióticos gentamicina e imipenem contra as bactérias Pseudomonas aeruginosa e Escherichia coli. No entanto, apresenta antagonismo em associação com amicacina, gentamicina e imipenem contra as três bactérias estudadas. Para além da ciprofloxacina não demonstrou resultados relevantes. Em relação com a atividade citotóxica, a concentração letal média (LC50) expôs um valor de 263,12 [ig/ml. Conclusão: finalmente, revelou-se que a H. martiusii apresenta atividade citotóxica sinérgica contra as bactérias avaliadas.

Resumen Introducción: la especie Hyptis martiusii Benth, comúnmente llamada "cidreira do campo", tiene múltiples propiedades biológicas, como ser insecticida, antifúngica y antiinflamatoria. El objetivo de este estudio fue investigar la actividad moduladora del aceite esencial de las hojas frescas de Hyptis martiusii en asociación con diferentes antibióticos contra las bacterias Staphylococcus aureus, Escherichia coli y Pseudomonas aeruginosa, y evaluar la actividad citotóxica de la especie. Materiales y métodos: el estudio utilizó la concentración mínima inhibitoria (CMI) como una forma de evaluar la modulación con una inoculación de 100 microlitros de cada cepa bacteriana. Las pruebas de citotoxicidad se realizaron mediante cultivo in vitro de células de tejido conectivo de ratón (fibroblastos de mamíferos). Resultados: la investigación demostró que el aceite esencial de las hojas de Hyptis martiusii Benth (OEHM) presenta sinergismo solo en asociación con los antibióticos gentamicina e imipenem contra las bacterias Pseudomonas aeruginosa y Escherichia coli. Sin embargo, presenta antagonismo en asociación con amikacina, gentamicina e imipenem contra las tres bacterias estudiadas. Además de la ciprofloxacina, no demostró resultados relevantes. En relación con la actividad citotóxica, la concentración letal media (CL50) exhibió un valor de 263,12 [ig/ml. Conclusión: finalmente, se reveló que la H. martiusii presenta actividad citotóxica sinérgica contra las bacterias evaluadas.

Abstract Introduction: The species Hyptis martiusii Benth. commonly called "cidreira do campo" has multiple biological properties, such as antifungal, anti-inflammatory, and insecticide. The aim of this study was to investigate the modulating activity of the essential oil of the fresh leaves of Hyptis martiusii in association with different antibiotics against the bacteria Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa, as also the cytotoxic activity of this species. Materials and methods: The study used the MIC (minimum inhibitory concentration) as a way of assessing the modulation using an inoculation of 100 microliters of each bacterial strain. The cytotoxicity tests were conducted using in vitro culture of mouse connective tissue cells (fibroblasts of mammals). Results: The research demonstrated that the essential oil from leaves of Hyptis martiusii Benth (OEHM) presented synergism only when associated with the antibiotics gentamicin and imipenem against the bacteria Pseudomonas aeruginosa and Escherichia coli. However, it presented antagonism in association with amikacin, gentamicin and imipenem against the three studied bacteria. In addition to the ciprofloxacin showed no relevant results. In relation to the cytotoxic activity the lethal concentration (LC50) exhibited a value of 263.12 [ig/ml. Conclusion: Ultimately it was established, that H. Martiusii presents a synergistic cytotoxic activity against the evaluated bacteria.

Modulação in vitro da atividade antibiótica pelo óleo essencial dos frutos de Piper tuberculatum Jacq / In vitro modulation of the antibiotic activity of essential oil from fruits of Piper tuberculatum Jacq

Introdução: Piper tuberculatum Jacq., popularmente conhecida como pimenta-longa ou pimenta-d'Arda, é utilizada empiricamente no tratamento de doenças respiratórias (asma, bronquite e tosse) e digestivas (dores abdominais e diarreias). Na literatura é descrita com importantes atividades anti-inflamatória, antimicrobiana, antileucêmico e anti-helmíntica. Objetivos: avaliar a atividade moduladora do óleo essencial dos frutos de P. tuberculatum (OEPT) em associação com diferentes antibióticos frente à Staphylococcus aureus, Escherichia coli e Pseudomona aeruginosa. Metodos: Os frutos (frescos) de P. tuberculatum foram coletados em Barbalha/CE e submetidos à hidrodestilação em aparelho tipo Clevenger para ser extraído o óleo essencial, após a extração o óleo essencial foi tratado com sulfato de sódio anidro para eliminação da umidade residual. A avaliação da atividade antibacteriana e modulação (em resistência bacteriana) frente às cepas de S. aureus (SA358), E. coli (EC27) e P. aeruginosa (PA03) foram determinadas pelo método de microdiluição para identificar a concentração inibitória mínima (CIM), realizada em triplicata. CIM de ≤ 256 µg/mL foi considerado clinicamente relevante. Resultados: a atividade antibacteriana do OEPT exibiu um CIM de ≥ 1024 µg/mL contra as cepas de bactérias de padrão resistente...(AU)

Introducción: Piper tuberculatum Jacq. popularmente conocida como pimenta-longa o pimenta-d'Arda, se utiliza empíricamente en el tratamiento de enfermedades respiratorias (asma, bronquitis y tos) y digestivas (dolor abdominal y diarrea). En la literatura es describe con importantes actividades antiinflamatorias, antimicrobianas, antileucémicas y antihelmínticas. Objetivo: evaluar la actividad moduladora de los aceites esenciales de frutos de P. tuberculatum (AEPT) en asociación con diferentes antibióticos contra Staphylococcus aureus, Escherichia coli y Pseudomona aeruginosa. Metodología: los frutos (frescos) de P. tuberculatum fueron recolectados en Barbalha/CE y sometidos a hidrodestilación en un equipo Clevenger, para extraer el aceite essencial (AEPT), el cual, una vez extraído, fue tratado con sulfato de sodio anhidro para eliminar la humedad residual. Se evaluó su actividad antibacteriana contra las cepas de S. aureus (SA358), E. coli (EC27) y P. aeruginosas (PA03). Empleando el método de microdilución se determinó la concentración inhibitoria mínima (CIM), con tres réplicas por cada tratamiento. Un valor de CIM ≤ 256 µg/mL se considera clínicamente...(AU)

Introduction: Piper tuberculatum Jacq., commonly known as pimenta-longa or pimenta-d'Arda, is empirically used to treat respiratory conditions (asthma, bronchitis and coughing) and digestive disorders (abdominal pain and diarrhea). Reference may be found in the literature to outstanding antiinflammatory, antimicrobial, antileukemic and antihelmintic activity. Objective: Evaluate the modulatory activity of essential oils from fruits of P. tuberculatum (AEPT) combined with various antibiotics againstStaphylococcus aureus, Escherichia coli and Pseudomona aeruginosa. Methods: Fresh fruits of P. tuberculatum were collected in Barbalha, CE, and subjected to hydrodistillation in a Clevenger set to extract the essential oil (AEPT). The oil extracted was then treated with anhydrous sodium sulfate to eliminate residual humidity. Antibacterial activity was evaluated against strains of S. aureus (SA358), E. coli (EC27) and P. aeruginosas (PA03). Minimum inhibitory concentration (MIC) was determined by the microdilution method, with three replications for each treatment. A MIC ≤ 256 µg/mL was considered to be clinically relevant. Results: Antibacterial activity of AEPT displayed a MIC of ≥1024 µg/mL against standard strains of multi-drug resistant bacteria. In fact, activity of AEPT antagonized the effect of amikacin against...(AU)

Modulação in vitro da atividade antibiótica pelo óleo essencial dos frutos de Piper tuberculatum Jacq / Modulación in vitro de la actividad antibiótica por el aceite esencial de frutos de Piper tuberculatum Jacq / In vitro modulation of the antibiotic activity of essential oil from fruits of Piper tuberculatum Jacq

Introdução: Piper tuberculatum Jacq., popularmente conhecida como pimenta-longaou pimenta-d'Arda, é utilizada empiricamente no tratamento de doenças respiratórias (asma, bronquite e tosse) e digestivas (dores abdominais e diarreias). Na literatura é descrita com importantes atividades anti-inflamatória, antimicrobiana, antileucêmico e anti-helmíntica. Objetivos: avaliar a atividade moduladora do óleo essencial dos frutos de P. tuberculatum (OEPT) em associação com diferentes antibióticos frente à Staphylococcus aureus, Escherichia coli e Pseudomona aeruginosa. Metodos: Os frutos (frescos) de P. tuberculatum foram coletados em Barbalha/CE e submetidos à hidrodestilação em aparelho tipo Clevenger para ser extraído o óleo essencial, após a extração o óleo essencial foi tratado com sulfato de sódio anidro para eliminação da umidade residual. A avaliação da atividade antibacteriana e modulação (em resistência bacteriana) frente às cepas de S. aureus (SA358), E. coli (EC27) e P. aeruginosa (PA03) foram determinadas pelo método de microdiluição para identificar a concentração inibitória mínima (CIM), realizada em triplicata. CIM de ≤ 256 µg/mL foi considerado clinicamente relevante. Resultados: a atividade antibacteriana do OEPT exibiu um CIM de ≥ 1024 µg/mL contra as cepas de bactérias de padrão resistente a múltiplas drogas. Na avaliação da atividade moduladora, o OEPT antagonizou o efeito da amicacina contra E. coli e S. aureus, mas teve efeito sinérgico contra P. aeruginosa. Combinado com a getamicina o óleo exibiu antagonismo frente a E. coli, no entanto não apresentou resultado relevante contra S. aureas e P. aeruginosa. A associação do OEPT com o antibiótico imipenem resultou efeito mais relevante, apresentando sinergismo para todas as bactérias avaliadas, por outro lado, em associação com ciprofloxacino não apresentou efeito significante em relação ao controle. Conclusão: O OEPT apresentou uma melhor atividade quando associado ao imipenem frente todas as bactérias avaliadas, mostrando ser uma possível alternativa no desenvolvimento de novos fármacos com atividade antibacteriana advindos de produtos fitoterápicos(AU)

Introducción: Piper tuberculatum Jacq. popularmente conocida como pimenta-longa o pimenta-d'Arda, se utiliza empíricamente en el tratamiento de enfermedades respiratorias (asma, bronquitis y tos) y digestivas (dolor abdominal y diarrea). En la literatura es describe con importantes actividades antiinflamatorias, antimicrobianas, antileucémicas y antihelmínticas. Objetivo: evaluar la actividad moduladora de los aceites esenciales de frutos de P. tuberculatum (AEPT) en asociación con diferentes antibióticos contra Staphylococcus aureus, Escherichia coli y Pseudomona aeruginosa. Metodología: los frutos (frescos) de P. tuberculatum fueron recolectados en Barbalha/CE y sometidos a hidrodestilación en un equipo Clevenger, para extraer el aceite essencial (AEPT), el cual, una vez extraído, fue tratado con sulfato de sodio anhidro para eliminar la humedad residual. Se evaluó su actividad antibacteriana contra las cepas de S. aureus (SA358), E. coli (EC27) y P. aeruginosas (PA03). Empleando el método de microdilución se determinó la concentración inhibitoria mínima (CIM), con tres réplicas por cada tratamiento. Un valor de CIM ≤ 256 µg/mL se considera clínicamente relevante. Resultados: la actividad antibacteriana del AEPT exhibió una CIM ≥ 1024 µg/mL contra las cepas estándar de bacterias resistentes a múltiples fármacos. En efecto, la actividad AEPT antagoniza el efecto de amikacina contra E. coli y S. aureus, pero tenía un efecto sinérgico contra P. aeruginosa. Combinado con la getamicina el aceite exhibió antagonismo contra E. coli, sin embargo no presentó resultado relevante ante S. aureus y P. aeruginosa. La asociación de AEPT con el antibiótico imipenem resultó el efecto más relevante, mostrando sinergismo frente a todas las bacterias evaluadas. Por el contrario, en asociación con ciprofloxacina no mostró ningún efecto significativo con respecto al control. Conclusión: el AEPT presentó una mejor actividad cuando se asoció a imipenem, frente todas las bacterias evaluadas, demostrando ser una posible alternativa en el desarrollo de nuevos fármacos con actividad antimicrobiana, a partir de productos herbarios(AU)

Introduction: Piper tuberculatum Jacq., commonly known as pimenta-longa or pimenta-d'Arda, is empirically used to treat respiratory conditions (asthma, bronchitis and coughing) and digestive disorders (abdominal pain and diarrhea). Reference may be found in the literature to outstanding antiinflammatory, antimicrobial, antileukemic and antihelmintic activity. Objective: Evaluate the modulatory activity of essential oils from fruits of P. tuberculatum (AEPT) combined with various antibiotics againstStaphylococcus aureus, Escherichia coli and Pseudomona aeruginosa. Methods: Fresh fruits of P. tuberculatum were collected in Barbalha, CE, and subjected to hydrodistillation in a Clevenger set to extract the essential oil (AEPT). The oil extracted was then treated with anhydrous sodium sulfate to eliminate residual humidity. Antibacterial activity was evaluated against strains of S. aureus (SA358), E. coli (EC27) and P. aeruginosas (PA03). Minimum inhibitory concentration (MIC) was determined by the microdilution method, with three replications for each treatment. A MIC ≤ 256 µg/mL was considered to be clinically relevant. Results: Antibacterial activity of AEPT displayed a MIC of ≥1024 µg/mL against standard strains of multi-drug resistant bacteria. In fact, activity of AEPT antagonized the effect of amikacin against E. coli and S. aureus, but had a synergic effect against P. aeruginosa. Combined with gentamicin, the oil exhibited antagonism against E. coli, but no relevant result was obtained against S. aureus and P. aeruginosa. Combination of AEPT with the antibiotic imipenem had the most relevant effect, displaying synergism against all the bacteria evaluated. However, in combination with ciprofloxacin it did not show any significant effect with respect to the control. Conclusion: AEPT displayed better activity against all the bacteria evaluated when combined with imipenem, proving to be a possible alternative for the development of new herbal drugs with antimicrobial activity(AU)

Avaliação da atividade anti-Leishmania e anti-Trypanosoma do extrato etanólico das folhas de Annona squamosa L / Evaluation of the anti-leishmania and anti-trypanosoma activity of ethanolic extract from the leaves of Annona squamosa L

As doenças parasitárias, também chamadas de “doenças negligenciadas”, continuam sendo uma grande dificuldade para o desenvolvimento social e econômico dos países mais pobres. Podemos citar como exemplo dessas doenças, a leishmaniose e a doença de Chagas. A leishmaniose é causada por parasitas do gênero Leishmania e afeta cerca de 12 milhões de pessoas. A doença de Chagas, causada pelo protozoário Trypanosoma cruzi, causa aproximadamente 50.000 mortes por ano. Os fármacos disponíveis para o tratamento dessas doenças são altamente tóxicos, sendo este um dos motivos que leva à busca por drogas eficazes e seguras para seus tratamentos. As folhas da Annona squamosa, espécie da família Annonaceae, já foram descritas na literatura por suas atividades hepatoprotetora, antiparasitária, pesticida e antimicrobiana. Nesse estudo avaliamos a atividade anti-leishmania e tripanocida do extrato etanólico das folhas de Annona squamosa L. (EEAS) em formas promastigota do parasita Leishmania braziliensis e Leishmania infantum e epimastigota de Trypanosoma cruzi, além de avaliar a atividade citotóxica em fibroblasto. Os resultados demonstram que o extrato apresentou uma melhor atividade contra Leishmania infantum e Leishmania brasiliensis quando comparados com Trypanosoma cruzi; e que apresentou uma maior toxicidade nas concentrações de 500 e 1000 μg/ml, com mortalidade dos fibroblastos de aproximadamente 85% e 100%, respectivamente. Esse estudo aponta para uma perspectiva terapêutica alternativa que se mostrou eficaz frente aos parasitas aqui estudados, exceto a forma epimastigota de Trypanosoma cruzi. Com relação aos testes de citotoxicidade fazem-se necessários novos testes, uma vez que apresentou um alto nível de toxicidade, viabilizando assim futuros ensaios in vivo.

The parasitic diseases, also calls by “neglected diseases”, continue being a major difficulty for the social and economic development of the poorest countries. We can cite as an example of these diseases, the leishmaniasis and the Chagas disease. Leishmaniasis is caused by parasites of the genus Leishmania and affects about 12 million people. The Chagas disease, caused by the protozoan Trypanosoma cruzi, causes approximately 50,000 deaths per year. The drugs available for the treatment of these diseases are highly toxic, being this one of the reasons that leads to the search for effective and safe drugs for their treatments. The leaves of the Annona squamosa, species of the family Annonaceae, have already been described in the literature by their hepatoprotective activities, antiparasitic, pesticide and antimicrobial. In this study we assessed the activity tripanocidal and antileishmania of ethanolic extract from the leaves of Annona squamosa L. (EEAS) in promastigota forms of the parasite Leishmania braziliensis and Leishmania infantum and epimastigota of Trypanosoma cruzi, in addition to evaluating the cytotoxic activity in fibroblasts. The results demonstrate that the extract presented a better activity against Leishmania infantum and Leishmania brasiliensis when compared with Trypanosoma cruzi; and which presented a greater toxicity at concentrations of 500 and 1000 μg/ml, with mortality of fibroblasts of approximately 85% and 100%, respectively. This study points to an alternative therapeutic perspective that showed effective against the parasites here studied, except the epimastigota form of Trypanosoma cruzi. With relation to cytotoxicity tests are required new tests, once presented a high level of toxicity, thus enabling future in vivo assays.