Análise da eficácia do uso terapêutico da trimetazidina nas principais síndromes coronarianas agudas

A injúria de reperfusão, ou isquemia, é um mecanismo fisiopatológico que ocorre nas etiopatogenias do miocárdio, como na angina instável. Assim, são utilizados fármacos adjuvantes citoprotetores, como a trimetazidina (TMZ), que visam à diminuição do tempo de hospitalização e melhora na função cardíaca com ação profilática contra essa lesão. No entanto, apesar dos seus potenciais benefícios no tratamento da síndrome coronariana aguda, ainda não está clara a sua eficácia em relação a outras terapias disponíveis. Nesse sentido, o objetivo do estudo é analisar a eficácia do uso terapêutico da trimetazidina nas principais síndromes coronarianas agudas. Foi realizada uma revisão sistemática usando as bases de dados PubMed, Cochrane Library e Embase. Um total de 3 estudos foi incluído na análise. Os resultados mostraram que a terapia com trimetazidina reduziu significativamente a incidência de eventos cardíacos adversos maiores (ECAM) (OR = 0,33, IC 95% 0,15-0,75, p = 0,007), menor dano miocárdico (p < 0,05) e fração de ejeção ventricular esquerda mais elevada e menos eventos adversos em comparação com o grupo placebo (p < 0,05). Não foram observadas diferenças significativas entre os grupos de trimetazidina e controle em termos de mortalidade por todas as causas, mortalidade cardiovascular ou incidência de eventos adversos. Os resultados deste estudo sugerem que a terapia adjuvante com trimetazidina pode melhorar os resultados clínicos e a função cardíaca em pacientes com IAM sem aumentar o risco de eventos adversos. No entanto, são necessários mais ensaios clínicos randomizados em larga escala para confirmar esses resultados e determinar a duração e dose ideais da terapia com trimetazidina nessa população de pacientes

Desenvolvimento de processos químicos sustentáveis para extração de carotenoides de Bactris gasipaes: aplicações tecnológicas e nutricionais

Carotenoids are natural pigments present in vegetables, animals and algae. Due to their hydrophobicity, carotenoids are usually extracted and synthesized by volatile organic solvents (COSs), restricting their potential applications, since they have low extraction selectivity, and an inherent toxicological potential (even in a low residual level in the final extract). In the food industry, these pigments have a big important sensory role, attributing an orange-redish color to the products, and important health benefits, since they act in important anti-inflammatory and antioxidant biochemical pathways. Commercially, synthetic carotenoids are more used than natural ones. However, the current market trend predicts that synthetic dyes will be sooner replaced by natural ones. Thus, alternative strategies, mainly based on the sustainability and green chemistry principles are excellent ways to mitigating the toxicity of the extracts and to create new integrated benign extraction platforms. Therefore, non-volatile solvents, such as ionic liquids (ILs), can be considered a promising alternative for replacing (or decreasing) the use of non-benign solvents. ILs are molten salts formed by large cations and organic or inorganic anions that vary in their dimensions. ILs have high thermal and chemical stability, negligible volatility in most cases and are known to be high performance solvents, capable of improving the extraction yield of natural compounds when compared to VOS-mediated processes. As a model, Bactris gasipaes fruits (peach palm) were used. This biomass are from Amazonian region, rich in carotenoids, namely all-isomers of carotene and lycopene, little explored commercially, being wasted in many cultivation systems, since the main commercial target of the species is the palm heart, a food delicacy of high economic value, which represents a predatory farming system. In this work, based on the principles of green chemistry and the concepts of biorefinery and circular economy, the valorization of the peach palm fruit was carried out. In particular, two IL-mediated carotenoid extraction platforms were developed, with low environmental impact (assessed by low carbon footprint and E-factor metrics), with solvent and raw material recycling, with optimized extraction operational conditions, which provided carotenoid extracts with high antioxidant activity, high thermal stability, and high yield compared to VOSmediated processes. In addition, the extracts were evaluated for their bioaccessibility and cellular uptake, using in vitro digestion assays of Caco-2 cells. Bioproducts enriched with carotenoids were developed, namely a vegan mayonnaise sauce, and a biodegradable packaging film. Finally, the extracts (obtained by ILs and VOS) were compared in terms of their biological activity, by an in vivo experimental assay, using Wistar rats, submitted to a high-fat diet for 7 days. Pro- and antiinflammatory cytokines, as well as oxidative stress markers were analyzed, with extracts obtained by ILs capable of raising the levels of anti-inflammatory and antioxidant markers, contrasting with the results found for extracts mediated by VOS.Os carotenoides são pigmentos naturais presentes em vegetais, animais e algas. Devido sua hidrofobicidade, são usualmente extraídos e sintetizados por solventes orgânicos convencionais voláteis (VOS), restringindo potenciais aplicações, visto que possuem baixa seletividade de extração, além de toxicidade inerente mesmo com baixo nível residual no extrato. No ramo alimentar, estes pigmentos desempenham um importante papel sensorial, atribuindo coloração alaranjado-avermelhado aos produtos, além de benefícios à saúde, por atuarem em importantes vias anti-inflamatórias e antioxidantes. Comercialmente, os carotenoides sintéticos são os mais demandados. Entretanto, a atual tendência de mercado prevê que corantes sintéticos sejam substituídos pelos naturais. Por isso, estratégias alternativas, embasadas nos princípios de sustentabilidade e de química verde são uma excelente estratégia para minimizar a toxicidade dos extratos e para construção de novas plataformas integradas de extração, que sejam mais benignas ao ambiente e ao consumidor. Sendo assim, solventes não voláteis, como líquidos iônicos (IL), podem ser considerados uma alternativa promissora para a substituição (ou diminuição) do uso de VOS. Os IL são sais fundidos formados por cátions de grandes dimensões e ânions orgânicos ou inorgânicos que variam em suas dimensões. Estes apresentam elevada estabilidade térmica e química, volatilidade desprezável na maioria dos casos, e são conhecidos por serem solventes de alta performance, capazes de melhorar o rendimento de extração de metabólitos naturais quando comparado aos processos mediados por VOS. Como modelo de estudo, frutos da palmeira Bactris gasipaes (pupunha) foram utilizados. Esta biomassa possui origem amazônica, rica em carotenoides, nomeadamente isômeros de caroteno e licopeno, pouco explorada comercialmente, sendo rejeitada em muitos sistemas de cultivo, pois o principal alvo comercial desta espécie é o palmito, iguaria alimentar de alto valor econômico agregado, mas que representa um cultivo predatório ao ecossistema. Neste trabalho, pautado nos princípios da química verde e nos conceitos de biorrefinaria e economia circular, a valorização do fruto da pupunha foi realizada. Nomeadamente, foram desenvolvidas duas plataformas de extração de carotenoides mediadas por IL, de baixo impacto ambiental (avaliadas por métricas de pegada de carbono e fator-E), com reciclagem de solventes e matérias-primas, além da otimização das condições operacionais de extração, que proporcionaram extratos de carotenoides com elevada atividade antioxidante, estabilidade térmica, e alto rendimento comparado aos processos mediados por VOS. Além disso, os extratos foram avaliados quanto a sua bioacessibilidade e uptake celular, utilizando ensaios de digestão in vitro e células Caco-2. Bioprodutos enriquecidos de carotenoides foram desenvolvidos, nomeadamente um molho do tipo maionese vegano, e uma embalagem biodegradável. E, por fim, os extratos (obtidos por IL e VOS) foram comparados quanto a sua atividade biológica, por meio de ensaio experimental in vivo, utilizando ratos da linhagem Wistar, submetidos à dieta hiperlipídica por 7 dias. Citocinas pró- e anti-inflamatórias, bem como marcadores de estresse oxidativo foram analisados, sendo os extratos obtidos por IL capazes de elevar os níveis dos marcadores anti-inflamatórios e antioxidantes, contrapondo aos resultados encontrados para os extratos mediados por VOS.Dados abertos - Sucupira - Teses e dissertações (2021

Lactobacillus fermentation of jussara pulp leads to the enzymatic conversion of anthocyanins increasing antioxidant activity

Bacteria possessing an enzymatic system able to metabolize anthocyanins may play a major role in the production of compounds with different bioavailability and biological activity. In this study, Lactobacillus and Bifidobacterium strains were screened for the enzymatic activities of alpha-galactosidase, beta-galactosidase and beta-glucosidase. These strains were also screened for their ability to convert the anthocyanins from jussara. The nine evaluated strains produced at least two of the three enzymesthey were also capable of changing the main anthocyanin's chromatographic profile. The values of cyanidin 3-glucoside and cyanidin 3-rutinoside, following fermentation, ranged from 0 to 3217.7 and 4323.3 to 17190.9 mu g/100 mL of medium fermented, respectively. The Lactobacillus deubruekii strain was able to change the anthocyanins from jussara pulp more extensively. Therefore, a culture medium containing jussara pulp and glucose was optimized using the experimental design as a statistical tool. Medium maximization occurred with a mixture composing 20% jussara pulp and 10% glucose in which the microorganism was able to reach the highest enzymatic production as well as produce the most extensive conversion of the main anthocyanins. Protocatechuic acid was the main enzymatic bioconversion product identified following fermentation. In addition, there was an observed increase in antioxidant activity following the jussara pulp fermentation process.Sao Paulo Research Foundation (FAPESP)Fed Univ Sao Paulo UNIFESP, Dept Biosci, Silva Jardim Str 136, BR-11015020 Santos, SP, BrazilSao Paulo State Univ UNESP, Biosci Inst, Coastal Campus Sao Vicente, BR-11330900 Sao Vicente, SP, BrazilFed Univ Sao Paulo UNIFESP, Dept Biosci, Silva Jardim Str 136, BR-11015020 Santos, SP, BrazilFAPESP: 2014/09301-6Web of Scienc

Modulatory Effects of Guarana (Paullinia cupana) on Adipogenesis

Guarana (Paullinia cupana) is a plant originated in Brazil that presents a beneficial effect on body weight control and metabolic alterations. The aim of this study was to evaluate the effects of guarana on genes and miRNAs related to adipogenesis in 3T3L1 cells. The anti-adipogenic effect of guarana was evaluated by Oil Red-O staining. Gene and miRNA expression levels were determined by real time PCR. The Cebpα and β-catenin nuclear translocation were evaluated using immunocytochemistry. Our data indicated that the triglyceride-reducing effect of guarana was dose-dependent from 100 to 300 µg/mL (−12%, −20%, −24% and −40%, respectively, p < 0.0001). An up-regulation of the anti-adipogenic genes Wnt10b, Wnt3a, Wnt1, Gata3 and Dlk1 and a down-regulation of pro-adipogenic genes Cebpα, Pparγ and Creb1 were also observed. Furthermore, guarana repressed mmu-miR-27b-3p, mmu-miR-34b-5p and mmu-miR-760-5p, that contributed for up-regulation of their molecular targets Wnt3a, Wnt1 and Wnt10b. Additionally, cells treated with guarana presented an increase on β-catenin nuclear translocation (p < 0.0018). In summary, our data indicate that guarana has an anti-adipogenic potential due to its ability to modulate miRNAs and genes related to this process. Together our data demonstrate the important role of guarana as a putative therapeutic agent

Brazilian biodiversity fruits : discovering bioactive compounds from underexplored sources

Large segments of the Brazilian population still suffer from malnutrition and diet-related illnesses. In contrast, many native fruits have biodiversity and are underexploited sources of bioactive compounds and unknown to consumers. The phytochemical composition of nine underexplored Brazilian fruits was determined. Carotenoids and anthocyanins were identified and quantified by high performance liquid chromatography-photodiode array-tandem mass spectrometry (HPLC-PDA-MS/MS), and phenolic compounds and iridoids were identified by flow injection analysis-electrospray-ion trap-tandem mass spectrometry (FIA-ESI-IT-MS/MS); in total, 84 compounds were identified. In addition, the chemical structure and pathway mass fragmentation of new iridoids from jenipapo (Genipa americana) and jatoba (Hymenae coubaril) are proposed. The highest level of carotenoids was registered in pequi (Caryocar brasiliense; 10156.21 μg/100 g edible fraction), while the major total phenolic content was found in cambuci (Campomanesia coubaril; 221.70 mg GAE/100 g). Anthocyanins were quantified in jabuticaba (Plinia cauliflora; 45.5 mg/100 g) and pitanga (Eugenia uniflora; 81.0 mg/100 g). Our study illustrates the chemical biodiversity of underexplored fruits from Brazil, supporting the identification of new compounds and encouraging the study of more food matrixes not yet investigated67718601876CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQFUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESP303956/2015-12013/07914-8We thank the Biodiversity for Food and Nutrition Project, Brazilian Environmental Ministry, FUNBIO − Biodiversity Fund, Bioversity International, FAO, ONU − Environmental, and GEF − Global Environmental Facility for financial support. A.Z.M. thanks FAPESP (proc. 2013/07914-8). V.V.d.R. thanks CNPq (303956/2015-1

Phenolic isomers from plantago catharinea leaves: Isolation, identification, quantification and in vitro antioxidant activity

In this study we isolated two polyphenolic acids of m/z 639, called catharinol A and catharinol B, from Plantago catharinea L. (Plantaginaceae) leaves. Although presenting very similar structures, catharinol A showed higher antioxidant activity when compared with gallic acid and quercetin standards. These compounds are position isomers and present in their chemical structure the rare sugar D-allose. Molecules with similar constitution are known to have important biological activities such as antitumor and immunosuppressive. These compounds were isolated by high-performance liquid chromatography (HPLC) and characterized by mass spectrometry (FIA-ESI-IT-MS/MS) and nuclear magnetic resonance (NMR). This work is the first study on the chemical composition of P. catharinea and encourages the production of Plantago species as a good source of bioactive molecules

Anatomical differentiation and metabolomic profiling: a tool in the diagnostic characterization of some medicinal Plantago species

There is a large list of plants used by the population as medicine, but in some case the choice of the right plant becomes a real drawback in phytotherapy, since it is often difficult to differentiate morphologically between the active and inactive species. Plantago species are widely used throughout the world as analgesic, anti-inflammatory, expectorant, digestive and wound healing. Nonetheless, Plantago spp. share very strong morphological similarities, which hinders their correct botanical identification and, in addition, they are equivocally marketed by the same common name “Plantain”. Therefore, the establishment of a reliable approach to distinguish unambiguously closely related species arises as an important task in the development of herbal medicines. In this work, we report a method that combines anatomical leaf features and chemical composition of four Plantago species to generate a multivariate model, which allows the differentiation of these species. Descriptive leaf anatomy was converted into a binary matrix to create a qualitative/quantitative non-metric multidimensional scaling (nmMDS) based on Jaccard index. The main results show that P. lanceolata L. is the most distinct species, the only one that owns mesophyll isolateral, colateral vascular bundle and a glandular trichome with spindle cells. Plantago major L. also has a unique glandular trichome, with enlarged basal cell and collar cell. This statistical-based anatomical approach is suitable to solve similar drawbacks in plant medicines of any other plant-cases. In addition, it was generated a nmMDS to chemical markers by mass spectrometry (FIA–ESI–IT–MS), to define how similar the species are regarding their chemical composition. Plantago major showed all compounds evaluated and is the only species to have the compounds hellicoside (m/z 655) and lavandulifolioside (m/z 755). The conversion of anatomical features into statistical data with the chemical composition emerges as a useful approach toward the quantitative differentiation of morphologically close related specimens.Fil: Mesquita, Leonardo Mendes de Souza. Universidade de Sao Paulo; BrasilFil: Delevati Colpo, Karine. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Limnología "Dr. Raúl A. Ringuelet". Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo. Instituto de Limnología; ArgentinaFil: da Rocha, Cláudia Quintino. University of Maranhão ; BrasilFil: Gatte Picchi, Douglas. Universidade de Sao Paulo; BrasilFil: Pereira Tangerina, Marcelo Marucci. Universidade de Sao Paulo; BrasilFil: Zachello Nunes, Beatriz. Universidade de Sao Paulo; BrasilFil: Gonçalves Martins, Maria Bernadete. Universidade de Sao Paulo; BrasilFil: Vilegas, Wagner. Universidade de Sao Paulo; Brasi

Addendum: de Souza Mesquita, L.M., et al. Modulatory Effect of Polyphenolic Compounds from the Mangrove Tree Rhizophora mangle L. on Non-Alcoholic Fatty Liver Disease and Insulin Resistance in High-Fat Diet Obese Mice. Molecules, 2018, 23, 2114

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Modulatory Effect of Polyphenolic Compounds from the Mangrove Tree Rhizophora mangle L. on Non-Alcoholic Fatty Liver Disease and Insulin Resistance in High-Fat Diet Obese Mice

No scientific report proves the action of the phytochemicals from the mangrove tree Rhizophora mangle in the treatment of diabetes. The aim of this work is to evaluate the effects of the acetonic extract of R. mangle barks (AERM) on type 2 diabetes. The main chemical constituents of the extract were analyzed by high-performance liquid chromatography (HPLC) and flow injection analysis electrospray-iontrap mass spectrometry (FIA-ESI-IT-MS/MS). High-fat diet (HFD)-fed mice were used as model of type 2 diabetes associated with obesity. After 4 weeks of AERM 5 or 50 mg/kg/day orally, glucose homeostasis was evaluated by insulin tolerance test (kiTT). Hepatic steatosis, triglycerides and gene expression were also evaluated. AERM consists of catechin, quercetin and chlorogenic acids derivatives. These metabolites have nutritional importance, obese mice treated with AERM (50 mg/kg) presented improvements in insulin resistance resulting in hepatic steatosis reductions associated with a strong inhibition of hepatic mRNA levels of CD36. The beneficial effects of AERM in an obesity model could be associated with its inhibitory α-amylase activity detected in vitro. Rhizophora mangle partially reverses insulin resistance and hepatic steatosis associated with obesity, supporting previous claims in traditional knowledge