ABSTRACT
Extracellular adenosine 5'-triphosphate (ATP) triggers the P2X7 receptor (P2X7R) ionic channel to stimulate the release of the interleukin-IL-1ß cytokine into macrophages. The current study explored the reaction of six structurally diverse triazole derivatives on P2X7-mediated dye uptake into murine peritoneal macrophages. P2X7R activity determined by ATP-evoked fluorescent dye uptake. Triazole derivatives toxicity measured using dextran rhodamine exclusion based colorimetric assay. A740004 and BBG, both P2X7R antagonist, inhibited ATP-induced dye uptake. In contrast, the derivatives 5a, 5b, 5e, and 5f did not diminish P2X7R activity in concentrations until 100⯵M. 5c and 5d analogs caused a potent inhibitory activity on P2X7-induced dye uptake. Dextran Rhodamine exclusion measurements after 24â¯h of continuous treatment with triazole derivatives indicated a moderated toxicity for all molecules. In conclusion, this study showed that a series of new hybrid 1,2,3-triazolic naphthoquinones reduces P2X7R-induced dye uptake into murine macrophages. In silico analysis indicates a good pharmacokinetic profile and molecular docking results of these analogs indicate the potential to bind into an allosteric site located into the P2X7R pore and juxtaposed with the ATP binding pocket. In this manner, the compounds 5c and 5d may be used as a scaffold for new P2X7R inhibitors with reduced toxicity, and good anti-inflammatory activity.
Subject(s)
Naphthoquinones/chemistry , Purinergic P2X Receptor Antagonists/chemistry , Receptors, Purinergic P2X7/metabolism , Triazoles/chemistry , Allosteric Site , Animals , Binding Sites , Caco-2 Cells , Cell Line , Coloring Agents/metabolism , Humans , Macrophages/cytology , Macrophages/metabolism , Mice , Microsomes, Liver/metabolism , Molecular Docking Simulation , Permeability/drug effects , Protein Structure, Tertiary , Purinergic P2X Receptor Antagonists/metabolism , Purinergic P2X Receptor Antagonists/pharmacology , Receptors, Purinergic P2X7/chemistry , Triazoles/metabolism , Triazoles/pharmacologyABSTRACT
Carotenoids are pigments responsible for the yellow-reddish color of many foods and are related to important functions and physiological actions, preventing several chronic-degenerative diseases. The objective of this study was to confirm the carotenoid composition of jackfruit by high-performance liquid chromatography connected to photodiode array and mass spectrometry detectors (HPLC-PDA-MS/MS). The main carotenoids were all-trans-lutein (24-44%), all-trans-beta-carotene (24-30%), all-trans-neoxanthin (4-19%), 9-cis-neoxanthin (4-9%) and 9-cis-violaxanthin (4-10%). Either qualitative or quantitative differences, mainly related to the lutein proportion, were found among three batches of jackfruit. Since the fruits from batch A showed significantly lower contents for almost all carotenoids, it also had the lowest total carotenoid content (34.1 microg/100 g) and provitamin A value, whereas the total carotenoid ranged from 129.0 to 150.3 microg/100 g in the other batches. The provitamin A values from batches B and C were 3.3 and 4.3 microg RAE/100 g, respectively. The carotenoid composition of jackfruit was successfully determined, where 14 of the 18 identified carotenoids were reported for first time. Differences among batches may be due to genetic and/or agricultural factors.
Subject(s)
Artocarpus/chemistry , Carotenoids/analysis , Chromatography, High Pressure Liquid , Lutein/isolation & purification , Mass Spectrometry , Xanthophylls/isolation & purificationABSTRACT
OBJETIVO: O propósito deste estudo foi analisar os efeitos do resfriamento e do aquecimento sobre a flexibilidade dos músculos isquiotibiais, observando os efeitos agudos e crônicos. MÉTODOS: Quarenta voluntários foram aleatoriamente incluídos em um dos quatro grupos (n=10): 1) grupo controle; 2) grupo alongamento (técnica sustentar-relaxar) para os músculos isquiotibiais, por duas semanas consecutivas; 3) grupo alongamento precedido da aplicação de crioterapia (25 minutos) na região posterior da coxa e 4) grupo alongamento precedido de aquecimento com diatermia por ondas curtas (25 minutos). A avaliação da flexibilidade muscular foi realizada através de uma prancha acoplada a um sistema de goniometria, especialmente preparada para avaliar o ângulo extensor do joelho. RESULTADOS: Os três grupos experimentais aumentaram significativamente a ADM em relação ao grupo controle. Os ganhos médios diários, considerados efeitos agudos, mostraram diferenças significativas em favor do grupo submetido ao resfriamento, quando comparado aos demais (aumento de 2,6 ± 0,9º, 4,3 ± 1,5º e 2,4 ± 0,7º para os grupos 2, 3 e 4, respectivamente, p= 0,008). Em relação aos efeitos crônicos, não foi observada diferença significativa entre os três grupos experimentais, embora todos diferiram do controle (aumento de 1,5 ± 0,5º, 11,1 ± 6,1º, 14,4 ± 5,4º e 14,4 ± 6,2º, para os grupos 1, 2, 3 e 4, respectivamente). CONCLUSÕES: Sessões de alongamento, aplicadas diariamente, aumentaram significativamente a flexibilidade dos músculos isquiotibiais. Os efeitos agudos foram maiores no grupo submetido ao resfriamento, quando comparado aos grupos somente alongado ou aquecido. Os efeitos crônicos não foram influenciados pelo aquecimento nem pelo resfriamento.
OBJECTIVE: The aim of this study was to analyze the acute and chronic effects of cooling and warming on hamstring muscle flexibility. METHOD: Forty volunteers were randomly included in one of four groups (n=10): 1) control group; 2) stretching group, using a sustain-and-relax technique on the hamstring muscles, for two consecutive weeks; 3) stretching group preceded by applying cryotherapy (25 minutes) to the posterior thigh region; 4) stretching group preceded by warming using shortwave diathermy (25 minutes). Muscle flexibility was assessed using a board coupled to a goniometric system specially prepared for evaluating the extensor angle of the knee. RESULTS: The three experimental groups significantly increased their range of motion in relation to the control group. The mean daily gains (considered to be acute effects) showed significant differences in favor of the group subjected to cooling, in comparison with the other two (increases of 2.6 ± 0.9º, 4.3 ± 1.5º and 2.4 ± 0.7º for groups 2, 3 and 4, respectively, p= 0.008). With regard to chronic effects, there were no significant differences between the three experimental groups, but they all differed from the control group (increases of 1.5 ± 0.5º, 11.1 ± 6.1º, 14.4 ± 5.4º and 14.4 ± 6.2º, for groups 1, 2, 3 and 4, respectively). CONCLUSION: Stretching sessions applied daily significantly increased hamstring muscle flexibility. The acute effects were greatest in the group subjected to cooling, in comparison with the groups with stretching alone and stretching plus warming. The chronic effects were not influenced by warming or by cooling.
