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.

Anticonvulsant Activity of trans-Anethole in Mice.

Epilepsy is a chronic neurological disorder affecting 1-2% of world population, and one-third of patients are refractory to pharmacological treatment. This fact has stimulated research for new antiepileptic drugs and natural products have been an important source. trans-Anethole (TAN) is a phenylpropanoid, component of some essential oils, extracted from plants, and its effects have been little studied. Therefore, this study is aimed at investigating the TAN effect in classic seizure models and evaluate the electroencephalographic (EEG) profile of animals treated with this substance. For this, Swiss male mice (Mus musculus) were used, and the lethal dose was evaluated and subsequently submitted to the test maximal electroshock (MES), the pentylenetetrazole- (PTZ) induced seizure test, and the EEG profile. Initially, the LD50 for TAN was estimated in 1000 mg/kg (i.p.) dose and there was no sign of acute toxicity or death. In the MES test, TAN 300, i.p. (12.00 ± 2.9 s) and 400 mg/kg, i.p. (9.00 ± 4.4 s) doses was able to decrease tonic seizures duration induced by electric discharge (0.5 mA, 150 pulses/s, for 0.5 s). In the PTZ test (75 mg/kg, i.p.), TAN 400 mg/kg, i.p. increased the latency to myoclonic jerks (80.0 (56.0-134.0)), the latency totonic-clonic seizures (900.0 (861.0-900.0) and decrease seizure duration (0.0 (0.0-10.0)). No deaths were found in this groups compared to vehicle. EEG analysis showed an amplitude decrease of waves (ratio of baseline) in TAN 300 (1.82 ± 0.23) and 400 mg/kg (1.06 ± 0.16) groups. In this way, TAN at 400 mg/kg was able to inhibit and/or attenuate seizures by increasing the time for the onset of spasms and convulsions, as reducing the duration of seizures. The EEG profile corroborate with this results showing a reduction in the amplitude of waves compared to the PTZ group. Thus, TAN showed an anticonvulsant effect in all experimental models performed, behavioral and electroencephalographic.

Efecto antinociceptivo y antiinflamatorio del aceite esencial de Lippia pedunculosa Hayek y su complejo de inclusión de ß-ciclodextrina / Antinociceptive and anti-inflammatory effect of Lippia pedunculosa Hayek essential oil and its ß-cyclodextrin inclusion complex

Lippia pedunculosa Hayek (EOLp) presenta efectos tripanocidas y amebicidas. En este trabajo se estudia su aceite esencial en modelos experimentales de analgesia e inflamación una vez que la prevalencia del dolor en la población genera un gran sufrimiento y discapacidad, y los medicamentos que se usan con mayor frecuencia tienen efectos secundarios indeseables. También se evalúa si la formulación del complejo de inclusión EOLp/ß-ciclodextrina (ß-CD) fue capaz de mejorar la actividad antinociceptiva de la EOLp sola. Los datos se evaluaron mediante análisis de varianza (ANOVA), seguido de la prueba de Tukey. Las diferencias se consideraron significativas si p<0,05. EOLp presentó un mejor efecto antinociceptivo en comparación con el complejo de inclusión EOLp/ß-CD. De esta manera, las ciclodextrinas parecen no ser eficientes para aceites esenciales con sustancias de peróxido. Sin embargo, en peritonitis, EOLp redujo la migración total de leucocitos y los niveles de IL-1ß en el líquido peritoneal, lo que confirma su efecto antiinflamatorio. Los efectos observados sugieren que EOLp es una buena y prometedora opción para el tratamiento de la inflamación y los trastornos relacionados con el dolor.

Lippia pedunculosa Hayek (EOLp) presents tripanocid and amebicid effects. However essential oil needs to be further studied in experimental models of analgesia and inflammation once the prevalence of pain in the population generates great suffering and disability and the drugs most often used have undesirable side effects. We also evaluated whether the inclusion complex formulation EOLp/ß-cyclodextrin (ß-CD) was able to improve the antinociceptive activity of the EOLp alone. Data were evaluated by analysis of variance (ANOVA), followed by Tukey's test. Differences were considered significant if p<0.05. EOLp presented better antinociceptive effect when compared to the EOLp/ß-CD inclusion complex. Thus, cyclodextrins appear not to be efficient for essential oils with peroxide substances. However, in peritonitis, EOLp reduced total leucocyte migration and IL-1ß levels in the peritoneal fluid, which confirmed its anti-inflammatory effect. The observed effects suggest that EOLp is the best promising option for the treatment of inflammation and pain-related disorders.

RMD86, a thiophene derivative, promotes antinociceptive and antipyretic activities in mice.

Treatment of pain and fever remains an important challenge for modern medicine. Non-steroidal anti-inflammatory drugs (NSAIDs) are the pharmacological options most often used, but their frequent use exposes the patient to serious side effects and dangerous drug interactions. In this context, thiophene derivatives are promising therapeutic alternatives. In this study, we evaluated the in vivo and in silico antinociceptive and antipyretic properties of RMD86, a thiophene derivative. At 100 mg/kg, RMD86 induced no significant changes in the motor coordination of mice in the Rotarod test. At 25, 50, and 100 mg/kg RMD86 significantly reduced the number of abdominal contortions induced by acetic acid (antinociceptive activity) in mice when compared to the control. In the formalin test, for the first phase, there was a reduction in licking times at doses of 50 and 100 mg/kg. In the second phase, reduction occurred at all doses. In the hot plate test, RMD86 (at 100 mg/kg) increased latency time in the first 30 min. For antipyretic activity, RMD86, when compared to the reference drug acetaminophen (250 mg/kg), significantly reduced pyrexia at 30, 60, and 120 min, at dosages of 25, 50 and 100 mg/kg. Molecular docking studies revealed that RMD86 presents a greater number of interactions and lower energy values than both the co-crystallized ligand and the reference drug (meloxicam) against COX-1 and COX-2 isoenzymes. The results give evidence of the analgesic and antipyretic properties like NSAIDs suggesting its potential for pain therapy.

Antinociceptive Activity of Chemical Components of Essential Oils That Involves Docking Studies: A Review.

INTRODUCTION: Pain is considered an unpleasant sensory and emotional experience, being considered as one of the most important causes of human suffering. Computational chemistry associated with bioinformatics has stood out in the process of developing new drugs, through natural products, to manage this condition. OBJECTIVE: To analyze, through literature data, recent molecular coupling studies on the antinociceptive activity of essential oils and monoterpenes. DATA SOURCE: Systematic search of the literature considering the years of publications between 2005 and December 2019, in the electronic databases PubMed and Science Direct. ELIGIBILITY CRITERIA: Were considered as criteria of 1) Biological activity: non-clinical effects of an OE and/or monoterpenes on antinociceptive activity based on animal models and in silico analysis, 2) studies with plant material: chemically characterized essential oils and/or their constituents isolated, 3) clinical and non-clinical studies with in silico analysis to assess antinociceptive activity, 4) articles published in English. Exclusion criteria were literature review, report or case series, meta-analysis, theses, dissertations, and book chapter. RESULTS: Of 16,006 articles, 16 articles fulfilled all the criteria. All selected studies were non-clinical. The most prominent plant families used were Asteraceae, Euphorbiaceae, Verbenaceae, Lamiaceae, and Lauraceae. Among the phytochemicals studied were α-Terpineol, 3-(5-substituted-1,3,4-oxadiazol-2-yl)-N'-[2-oxo-1,2-dihydro-3H-indol-3-ylidene] propane hydrazide, ß-cyclodextrin complexed with citronellal, (-)-α-bisabolol, ß-cyclodextrin complexed with farnesol, and p-Cymene. The softwares used for docking studies were Molegro Virtual Docker, Sybyl®X, Vlife MDS, AutoDock Vina, Hex Protein Docking, and AutoDock 4.2 in PyRx 0.9. The molecular targets/complexes used were Nitric Oxide Synthase, COX-2, GluR2-S1S2, TRPV1, ß-CD complex, CaV1, CaV2.1, CaV2.2, and CaV2.3, 5-HT receptor, delta receptor, kappa receptor, and MU (µ) receptor, alpha adrenergic, opioid, and serotonergic receptors, muscarinic receptors and GABAA opioid and serotonin receptors, 5-HT3 and M2 receptors. Many of the covered studies used molecular coupling to investigate the mechanism of action of various compounds, as well as molecular dynamics to investigate the stability of protein-ligand complexes. CONCLUSIONS: The studies revealed that through the advancement of more robust computational techniques that complement the experimental studies, they may allow some notes on the identification of a new candidate molecule for therapeutic use.

Non-clinical study of the anxiolytic effect of Citrus aurantium L. essential oil in an inclusion complex with 2-hydroxypropyl-ß-cyclodextrin

Anxiety in the world population has increased significantly; the problem has encouraged studies regarding innovative alternatives for treatment. Research with Citrus aurantium L. essential oil (CEO) has revealed positive results with anxiolytic effects in both animals and humans. However, certain limitations affect its storage and preservation, its efficiency in therapy, and determination of adequate posologies. The potential use of cyclodextrins as drug carriers has been successfully explored. This study aims to assess the anxiolytic potential of a CEO/2-hydroxypropyl-ß-cyclodextrin (HP-ß-CD) inclusion complex. Preparation of the inclusion complex was performed using the Alpha 1-2 LDplus lyophilizer. To allow formation, and avoid loss of volatiles to the atmosphere, Limonene (LIM), the main compound in CEO, together with HP-ß-CD in a molar ratio of (1: 1M) was dispersed in ethanol for 36 hours using a laboratory shaker at room temperature (25°C). Non-clinical murine pharmacological tests were performed for anxiety assessment in experimental and control groups. To assess anxiety and motor impairment, the animals were evaluated using the elevated plus maze, open field, and rota-rod tests. Satisfactory results of the anxiolytic effect of the OEC complexed in HP-ß-CD were observed, with the indication of an potentiation of the effect with doses lower than 500 mg/kg and 250 mg/kg complexed, suggesting improvement in the anxiolytic properties of the OEC.

Auditoria em enfermagem: análise do processo, concepções e expectativas / Audit in nursing: process analysis, conceptions and expectations / Auditoría en enfermería: análisis del proceso, concepciones y expectativas

Objetivo: analisar o desenvolvimento da auditoria em enfermagem, investigando métodos, finalidades, indicadores, concepções e expectativas, em instituições pública e privadas de saúde. Método: estudo exploratório, descritivo, com abordagem qualitativa, realizado mediante entrevistas semiestruturadas com cinco enfermeiros auditores. As entrevistas foram analisadas pela técnica da análise de conteúdo. O projeto foi aprovado pelo Comitê de Ética em Pesquisa CAAE 13182213.5.0000.5188. Resultados: as unidades temáticas possibilitaram a construção das seguintes categorias de análise: métodos do processo de auditoria em enfermagem; indicadores do processo de auditoria em enfermagem; finalidades do processo de auditoria em enfermagem; concepção sobre a auditoria em enfermagem; expectativa para a auditoria em enfermagem. Conclusão: entre as instituições pública e privadas há diferenças quanto aos métodos, indicadores e finalidades do processo de auditoria. Com relação às concepções e expectativas, observa-se importância e tendência ao seu crescimento.(AU)

Objective: to analyze the development of audit in nursing with investigation of methods, purposes, indicators, conceptions and expectations in public and private health institutions. Method: exploratory, descriptive study with qualitative approach and carried out through semi-structured interviews with five auditor nurses. Interviews were analyzed by the content analysis technique. The project was approved by the Research Ethics Committee CAAE 13182213.5.0000.5188. Results: thematic units enabled the construction of the following categories of analysis: methods of nursing audit process; indicators of nursing audit process; purposes of audit process in nursing; conception on audit in nursing; expectation for audit in nursing. Conclusion: differences in methods, indicators and audit process purposes were observed between public and private institutions. The importance and tendency to growth is evident in conceptions and expectations.(AU)

Objetivo: analizar el desarrollo de la auditoría en la enfermería, investigando métodos, finalidades, indicadores, concepciones y expectativas, en instituciones públicas y privadas de salud. Método: estudio exploratorio, descriptivo, con enfoque cualitativo, realizado mediante entrevistas semi-estructuradas con cinco enfermeros auditores. Las entrevistas fueron analizadas por la técnica del análisis de contenido. El proyecto fue aprobado por el Comité de Ética en Investigación CAAE 13182213.5.0000.5188. Resultados: las unidades temáticas posibilitaron la construcción de las siguientes categorías de análisis: métodos del proceso de auditoría en enfermería; indicadores del proceso de auditoría en enfermería; finalidades del proceso de auditoría y enfermería; concepción sobre la auditoría en enfermería; expectativa para la auditoría en enfermería. Conclusión: entre las instituciones públicas y privadas hay diferencias entre los métodos, indicadores y finalidades del proceso de auditoría. Con relación a las concepciones y expectativas, se observó importancia y tendencia de su crecimiento.(AU)