GQ-16, a novel peroxisome proliferator-activated receptor (PPAR ) ligand, promotes insulin sensitization without weight gain

ABSTRACTBackground: PPAR agonists improve insulin sensitivity but also evoke weight gain. Results: GQ-16 is a PPAR partial agonist that blocks receptor phosphorylation by Cdk5 and improves insulin sensitivity in diabetic mice in the absence of weight gain. Conclusion: The unique binding mode of GQ-16 appears to be responsible for the compound’s advantageous pharmacological profile. Significance: Similar compounds could have promise as anti-diabetic therapeutics

Síntese, Modelagem Molecular e Atividade Hipoglicemiante de Novas Arilideno-Tiazolidinadionas

As glitazonas, também conhecidas como sensibilizadores de insulina, é a denominação genérica de uma série de tiazolidinadionas (TZDs) possuidoras de atividade hipoglicemiante administrada por via oral em pacientes com diabetes mellitus tipo 2. Dentre essas inclui a rosiglitazona e pioglitazona. No presente estudo, sintetizamos 12 derivados arilideno-tiazolidinadionas (ATZDs) da 5-benzilideno-3-(4-metil-benzil)-thiazolidina-2,4-diona com potencial atividade hipoglicemiante. Em seguida, investigamos os efeitos metabólicos e moleculares do composto 5- (4-cloro-benzilideno)-3-(4-metil-benzil)-tiazolidina-2,4-diona (GQ2) em camundongos swiss com obesidade induzida por dieta hiperlipidica (DH). As novas ATZDs, foram sintetizadas pela reação de adição nucleofílica da 3-(4-metil-benzil)-tiazolidina-2,4-diona com etil-(2-ciano-3- fenil)-acrilatos substituídos. De acordo com os estudos de modelagem molecular, os complexos formados entre as novas ATZDs e o domínio LBD do receptor PPARγ apresentaram boa estabilidade quando comparadas com a energia de ligação da rosiglitazona. O tratamento de camundongos obesos com GQ2 durante 14 dias reduziu os níveis basais de glicose, insulina e leptina associados a um aumento da sensibilidade à insulina, redução da gordura epididimal, com menor retenção de fluídos e concomitante redução no ganho de peso corporal. Quando nesse mesmo período foi avaliada a quantidade de ração ingerida, não foi detectada diferença significativa no consumo de ração durante 24 horas entre os animais tratados com GQ2 e DH. A via de sinalização da insulina, IR/IRSs/PI3K/Akt, que foi reduzida pela DH, apresentou recuperação completa após tratamento com GQ2 em fígado, músculo e tecido adiposo, acompanhados de redução da fosforilação do IRS-1ser307 em tecido adiposo e hepático. O tratamento com GQ2 levou ainda a redução da expressão da enzima iNOS em músculo e tecido adiposo, redução do TNF-α em tecido adiposo, paralelo a uma redução da ativação das serinas quinases IKK e JNK nos 3 tecidos estudados. Sendo assim, o novo agonista de PPARγ, GQ2, reduz a resistência à insulina e parece levar a um aumento da sensibilidade à insulina no fígado, músculo esquelético e tecido adiposo através de alterações da expressão e fosforilação de proteínas envolvidas na via de transmissão do sinal da insulina, via IR/IRSs/PI3K/Akt, em animais com resistência insulínica e obesidade induzida por dieta hiperlipídic

Psittacanthus plagiophyllus Eichl. (Loranthaceae): Perfil Fitoquímico, Efeito Gastroprotetor e Toxicidade Aguda

Made available in DSpace on 2017-06-02T11:10:32Z (GMT). No. of bitstreams: 2 license.txt: 1748 bytes, checksum: 8a4605be74aa9ea9d79846c1fba20a33 (MD5) 3.pdf: 765549 bytes, checksum: 27ced155ab4b931e600a548120cb1fb3 (MD5) Previous issue date: 1Universidade Federal do Oeste do Pará. Laboratório de Bioprospecção e Biologia Experimental. Santarém, Pará, Brasil.Universidade Federal do Oeste do Pará. Laboratório de Bioprospecção e Biologia Experimental. Santarém, Pará, Brasil.Universidade Federal do Oeste do Pará. Laboratório de Bioprospecção e Biologia Experimental. Santarém, Pará, Brasil.Psittacanthus plagiophyllus (Loranthaceae) é uma das espécies utilizadas no distrito de Alter do Chão, Santarém - PA, para o tratamento de gastrite. Levando em consideração o uso popular desta espécie, aliado à ausência de estudos farmacológicos e à sua grande disponibilidade nas savanas de Alter do Chão, o objetivo deste trabalho foi investigar o possível efeito gastroprotetor dos extratos aquoso e hidroalcólico das folhas de P. plagiophyllus contra lesões gástricas induzidas por etanol em ratos, além de sua toxicidade aguda em ratos e de seu perfil fitoquímico por Cromatografia em Camada Delgada. No perfil cromatográfico dos extratos foi identificada a presença de flavonoides, taninos hidrolisáveis e cumarinas. O extrato aquoso de P. plagiophyllus nas doses de 500 e 1000 mg/Kg e o hidroalcoólico na dose de 500 mg/Kg inibiram significativamente a formação de lesões gástricas induzidas por etanol em ratos, quando comparados ao grupo controle, pelo teste de Dunnett (p<0,05). No ensaio de toxicidade aguda não foram observados sinais tóxicos de caráter geral e nem morte dos animais até a dose de 5000 mg/Kg dos extratos, o que indica baixa ou nenhuma toxicidade. Os compostos fenólicos detectados em P. plagiophyllus podem estar relacionados ao efeito gastroprotetor evidenciado.Psittacanthus plagiophyllus (Loranthaceae) is one of the many species used in the district of Alter do Chão, Santarém - PA for the treatment of gastritis. Considering the popular use of this species, combined with the absence of pharmacological studies and its wide availability in the savanna of Alter do Chão, the aim of this study was to investigate the possible gastroprotective effect of hydroalcoholic and aqueous extracts of P. plagiophyllus leaves against ethanol-induced gastric lesions in rats, in addition to its acute toxicity in rats and phytochemical profile by Thin Layer Chromatography. The chromatographic profile of the extracts showed the presence of flavonoids, hydrolysable tannins and coumarins. The aqueous extract of P. plagiophyllus at doses of 500 and 1000 mg/Kg and hydroalcoholic at a dose of 500 mg/Kg significantly inhibited the formation of ethanol-induced gastric lesions in rats compared to the control group by the Dunnett's test (p <0.05). In the acute toxicity test were not observed signs of general toxic and no death of the animal to 5000 mg/Kg of the extracts, indicating low or no toxicity. Phenolic compounds found in P. plagiophyllus may be related to evidenced gastroprotective effect

Chemical composition and antimicrobial activity of the essential oil of Lippia grandis Schauer (Verbenaceae) from the western Amazon

AbstractLippia grandis Schauer is an aromatic plant that has been used as a spice in Brazilian culinary and in traditional medicine to treat liver disease, disorders of the stomach and throat infections. We determined the chemical composition of the essential oil of L. grandis and evaluated its potential for the treatment of clinically-important pathogenic micro-organisms. The essential oil was obtained by hydrodistillation and analyzed by gas chromatography-mass spectrometry (GC-MS), giving carvacrol (37.12%), ρ-cymene (11.64%), and thymol (7.83%) as the main components. The agar disk diffusion method of the essential oil was effective against 75% of the micro-organisms analyzed, in particular, Staphylococcus aureus, Enterococcus faecalis, and Escherichia coli. The minimum inhibitory concentration was 0.57mg/ml for E. faecalis and 1.15mg/ml for all the other strains. The results indicate that the essential oil of L. grandis contains chemical compounds with good potential for the treatment of infections

Chemical Composition And Antimicrobial Activity Of The Essential Oil Of Lippia Grandis Schauer (verbenaceae) From The Western Amazon.

Lippia grandis Schauer is an aromatic plant that has been used as a spice in Brazilian culinary and in traditional medicine to treat liver disease, disorders of the stomach and throat infections. We determined the chemical composition of the essential oil of L. grandis and evaluated its potential for the treatment of clinically-important pathogenic micro-organisms. The essential oil was obtained by hydrodistillation and analyzed by gas chromatography-mass spectrometry (GC-MS), giving carvacrol (37.12%), ρ-cymene (11.64%), and thymol (7.83%) as the main components. The agar disk diffusion method of the essential oil was effective against 75% of the micro-organisms analyzed, in particular, Staphylococcus aureus, Enterococcus faecalis, and Escherichia coli. The minimum inhibitory concentration was 0.57 mg/ml for E. faecalis and 1.15 mg/ml for all the other strains. The results indicate that the essential oil of L. grandis contains chemical compounds with good potential for the treatment of infections.1341474-

Mercurial exposure of residents of Santarém and Oriximiná cities (Pará, Brazil) through fish consumption

International audienceA survey of the mercurial exposure of residents of Santarém and Oriximiná showed a differential mercurial impregnation between men and women. At the level of both cities, the mean hair mercury concentrations were 1.5 ± 0.5 (90th and 95th percentiles: 2.8 and 4.3) and 2.52 ± 0.09 μg g Hg/g (90th and 95th percentiles: 4.7 and 8.1) for women and men, respectively. The mercurial contamination appeared significantly closely linked to the daily amount of consumed fish. Carnivore species pescada branca (Plagioscion squamosissimus) and apapá (Pellona castelnaeana) and non-carnivore species pacú (Mylossoma duriventre) and aracú (Schizodon fasciatus) were consumed by 22, 19, 55 and 25 % of people, respectively, and the mean mercury concentrations within fish flesh were 1.44 ± 0.11, 1.66 ± 0.19, 0.48 ± 0.09 and 0.49 ± 0.06 μg/g dry weight, respectively. Men aged above 35 were significantly more contaminated than those below. The mean hair concentrations of men were 5.20 ± 1.25 and 1.50 ± 0.22 μg/g, for those aged above 35 and below, respectively. The probability for women of childbearing age from both cities to present a hair mercury concentration above 1 μg Hg/g (corresponding to the US Environmental Protection Agency reference dose) was equal to 0.30 (95 % confidence interval of 0.24-0.36). The probability of hair mercury concentration to be above the lowest observable adverse effect level (LOAEL) (0.3 μg Hg/g) was equal to 0.79 (95 % confidence interval: 0.73-0.86)

Cultivo do Guaco (Mikania laevigata Sch. Bip. ex Baker) no Baixo Rio Amazonas e monitoramento de cumarina, seu principal constituinte ativo

Made available in DSpace on 2017-06-02T11:14:52Z (GMT). No. of bitstreams: 2 license.txt: 1748 bytes, checksum: 8a4605be74aa9ea9d79846c1fba20a33 (MD5) 1.pdf: 420593 bytes, checksum: 793743f9d7c2d428416aeec8b4e19d18 (MD5) Previous issue date: 23Universidade Federal do Oeste do Pará. Laboratório de Bioprospecção e Biologia Experimental. Santarém, PA, Brasil / Universidade Federal do Pará. Programa de Pós-Graduação em Química. Belém, PA, Brasil.Universidade Federal do Oeste do Pará. Laboratório de Bioprospecção e Biologia Experimental. Santarém, PA, Brasil / Universidade Federal do Oeste do Pará. Programa de Pós-Graduação em Recursos Naturais da Amazônia. Santarém, PA, Brasil.Universidade Federal do Oeste do Pará. Laboratório de Bioprospecção e Biologia Experimental. Santarém, PA, Brasil.Universidade Estadual de Campinas. Divisão de Agrotecnologia. CPQBA-UNICAMP. Campinas, SP, Brasil.Universidade Federal do Oeste do Pará. Programa de Pós-Graduação em Recursos Naturais da Amazônia. Santarém, PA, Brasil.Universidade Federal do Oeste do Pará. Laboratório de Bioprospecção e Biologia Experimental. Santarém, PA, Brasil / Universidade Federal do Pará. Programa de Pós-Graduação em Química. Belém, PA, Brasil / Universidade Federal do Oeste do Pará. Programa de Pós-Graduação em Recursos Naturais da Amazônia. Santarém, PA, Brasil.Universidade Federal do Oeste do Pará. Laboratório de Bioprospecção e Biologia Experimental. Santarém, PA, Brasil / Universidade Federal do Oeste do Pará. Programa de Pós-Graduação em Recursos Naturais da Amazônia. Santarém, PA, Brasil.Mikania laevigata (Asteraceae) é popularmente usada no tratamento de doenças respiratórias, incluindo asma, bronquite e tosse. No Brasil, extratos de guaco são usados como produtos medicinais autorizados pela Agência Nacional de Vigilância Sanitária (ANVISA). No estudo, avaliou-se a adaptação e influência da variação sazonal do guaco, em um cultivo mantido em Santarém, Estado do Pará, Brasil; além do monitoramento da cumarina, seu principal constituinte ativo. No cultivo do guaco, as variáveis climáticas e o teor de cumarina foram avaliados mensalmente. A cumarina foi analisada por CCD (Cromatografia em Camada Delgada) e quantificada por HPLC (Cromatografia Liquida de Alta Eficiência) com base nos extratos hidroalcoólico e aquoso das folhas desidratadas. Na estação chuvosa (janeiro a julho), o guaco teve um crescimento homogêneo. Na estação de estiagem (agosto a novembro) houve perda das plantas que cresciam a pleno sol. O teor de cumarina foi detectado durante o desenvolvimento da planta, com níveis que variaram de 0,470 ± 0,01% a 0,886 ± 0,063%. O tempo da coleta não influenciou no teor de cumarina nas plantas cultivadas com 50% de sombra, tendo a média de 0,712% no extrato hidroalcoólico e 0,744% no extrato aquoso. Baseado nos resultados, em condições de sombreamento parcial, assegurou-se que o cultivo do guaco no Baixo Rio Amazonas pode ser replicado pelos pequenos agricultores, em seus Arranjos Produtivos Locais (APL) de plantas medicinais.Mikania laevigata (Asteraceae) is popularly used in the treatment of respiratory diseases, including asthma, bronchitis, and cough. In Brazil, guaco extracts are used as medicinal products authorized by the National Health Surveillance Agency (ANVISA). In the study, it was evaluated the adaptation and the influence of the seasonal variation of guaco, in a cultivation held in Santarém, state of  Pará, Brazil, and a monitoring of coumarin, its primary active constituent. In the growing of guaco, the climate variables, and the coumarin content were evaluated monthly. The coumarin was analyzed by TLC (Thin Layer Chromatography) and quantified by HPLC (High Performance Liquid Chromatography) from hydroalcoholic and aqueous extracts of dried leaves. In the rainy season (january-july), the guaco had a homogeneous growth. In the dry season (august to november), there was loss of plants grown in full sun. The coumarin content was detected throughout the development of the plant, with levels that varied from 0.470 ± 0.01% to 0.886 ± 0.063%. The time of collection does not influenced in the coumarin content of the plants grown with 50% shade, having the mean of 0.712% in the hydroalcoholic extract and 0.744% in the aqueous extract. Based on the results, in partial shade conditions, it was ensured that small farmers could replicate the cultivation of guaco in the Lower Amazon River, in their local productive arrangements of medicinal plants

Ventilatory frequency and anesthetic efficacy in silver catfish, Rhamdia quelen: a comparative approach between different essential oils

ABSTRACT This study investigated the efficacy of essential oils of Lippia alba (EOLA) citral chemotype and Lippia origanoides (EOLO) and their effects on ventilatory frequency (VF) of silver catfish, Rhamdia quelen. Fish were exposed to 50-300 μL L−1 of EOLA and 25-300 μL L−1 of EOLO to determine induction times to sedation, anesthesia, and recovery. Moreover, VF was determined in fish exposed to 5 or 10 μL L−1 of EOLA and of EOLO for 8 h. The increasing concentration of essential oils proportionally decreased sedation and anesthesia induction times. The highest EOLA concentration increased VF of fish from the control group at 1 h of exposure, but VF decreased at both EOLO concentrations after 2 h. The EOLA citral chemotype and EOLO were effective sedatives and anesthetics for silver catfish. However, EOLO was the most suitable sedative for additional studies regarding fish transport as it reduced VF and did not induce VF increase in silver catfish. The EOLA citral chemotype and EOLO are effective sedatives and anesthetics for silver catfish. Moreover, the EOLO is recommended for transport of silver catfish, because it maintains the ventilatory frequency constant, avoiding a possible metabolic stress

Evaluation of the anti-snakebite, antimicrobial and antioxidant potential of Philodendron megalophyllum Schott (Araceae), traditionally used in accidents caused by snakes in the western region of Pará, Brazil

Ethnopharmacological relevance: In the region of Western Pará, Amazonia, Brazil, Philodendron megalophyllum is widely used for the treatment of envenomations caused by bites from venomous snakes. The traditional use of plants is usually done through oral administration of an infusion (decoction) soon after the bite occurs. The efficiency of aqueous extracts of P. megalophyllum was demonstrated for blocking the activity of the venom of Bothrops sp., but only for a pre-incubation protocol (venom:extract), which fails to simulate the real form of use of this species. In this context, the objective of this research was to evaluate the anti-snakebite potential of the aqueous extract of P. megalophyllum to inhibit for the biological activity induced by Bothrops atrox venom (BaV) using traditional treatment methods. Material and methods: Initially, an aqueous extract using the stem of P. megalophyllum (AEPm) was prepared following the standard procedure used by the residents of the rural area along the Tapajós River (Eixo Forte region) in Santarém, PA, Brazil. The phytochemical profile of AEPm was conducted using thin layer chromatography (TLC) and phenolic compounds were quantified through colorimetric trials. The cytotoxicity of AEPm was evaluated using the MRC-5 human fibroblast line, and the antioxidant potential was measured using DPPH methods and cell culture. AEPm antimicrobial action was evaluated by the 96-well plate microdilution and the minimum inhibitory concentration (MIC) methods using 18 types of microorganisms including bacteria that are present in the oral cavity of snakes. AEPm blocking potential was tested against BaV activity in vitro (fibrinolytic) and in vivo (defibrinating and hemorrhagic). In order to test for an interaction between BaV and AEPm SDS-PAGE electrophoresis was conducted. Results: The presence of coumarins, fatty acids, and hydrolysable tannins were detected in the AEPm. The colorimetric trials showed that AEPm had a high concentration of condensed tannins (20.1 ± 1.2%). The potential of AEPm for blocking of hemorrhagic and fibrinolytic activity of BaV showed a maximum reduction of 86.1% and 96.5%, respectively, for the pre-incubation protocol (1:10, venom:extract). However, when the extract was administered orally there was no significant blocking of these activities. The interaction of BaV and AEPm showed a modification of the profile of proteic bands when compared to the pattern of bands obtained from the BaV alone. The AEPm was not considered toxic, demonstrated antioxidant activity, and was capable of reducing the growth of 10 of the 18 studied microorganisms. Conclusion: Although the stem of P. megalophyllum is indicated by traditional medicine techniques as effective against snakebites, the extract, when tested orally was not able to significantly inhibit (p ˃ 0.05) hemorrhage and defibrinating activity induced by the B. atrox venom. On the other hand, the extract yielded a promising result with respect to antioxidant and antimicrobial potential, and after further studies it could be used as a complementary treatment for localized action and secondary infections that frequently occur with snakebites from the genus of Bothrops sp. © 2020 Elsevier Lt