RESUMO
Neuroinflammation is a condition associated with several types of dementia, such as Alzheimer's disease (AD), mainly caused by an inflammatory response to amyloid peptides that induce microglial activation, with subsequent cytokine release. Neuronal caspase-1 from inflammasome and cathepsin B are key enzymes mediating neuroinflammation in AD, therefore, revealing new molecules to modulate these enzymes may be an interesting approach to treat neurodegenerative diseases. In this study, we searched for new caspase-1 and cathepsin B inhibitors from five species of Brazilian marine invertebrates (four cnidarians and one echinoderm). The results show that the extract of the box jellyfish Chiropsalmus quadrumanus inhibits caspase-1. This extract was fractionated, and the products monitored for their inhibitory activity, until the obtention of a pure molecule, which was identified as trigonelline by mass spectrometry. Moreover, four extracts inhibit cathepsin B, and Exaiptasia diaphana was selected for subsequent fractionation and characterization, resulting in the identification of betaine as being responsible for the inhibitory action. Both molecules are already found in marine organisms, however, this is the first study showing a potent inhibitory effect on caspase-1 and cathepsin B activities. Therefore, these new prototypes can be considered for the enzyme inhibition and subsequent control of the neuroinflammation.
Assuntos
Doença de Alzheimer , Catepsina B , Humanos , Animais , Caspase 1/farmacologia , Inflamassomos , Microglia , Doenças Neuroinflamatórias , Organismos Aquáticos , Betaína , Citocinas , Peptídeos/farmacologia , Invertebrados , Peptídeos beta-Amiloides/farmacologiaRESUMO
Neuroinflammation is a condition associated with several types of dementia, such as Alzheimer’s disease (AD), mainly caused by an inflammatory response to amyloid peptides that induce microglial activation, with subsequent cytokine release. Neuronal caspase-1 from inflammasome and cathepsin B are key enzymes mediating neuroinflammation in AD, therefore, revealing new molecules to modulate these enzymes may be an interesting approach to treat eurodegenerative diseases. In this study, we searched for new caspase-1 and cathepsin B inhibitors from five species of Brazilian marine invertebrates (four cnidarians and one echinoderm). The results show that the extract of the box jellyfish Chiropsalmus quadrumanus inhibits caspase-1. This extract was fractionated, and the products monitored for their inhibitory activity, until the obtention of a pure molecule, which was identified as trigonelline by mass spectrometry. Moreover, four extracts inhibit cathepsin B, and Exaiptasia diaphana was selected for subsequent fractionation and characterization, resulting in the identification of betaine as being responsible for the inhibitory action. Both molecules are already found in marine organisms, however, this is the first study showing a potent inhibitory effect on caspase-1 and cathepsin B activities. Therefore, these new prototypes can be considered for the enzyme inhibition and subsequent control of the neuroinflammation.
RESUMO
Umbu, a common fruit from the northeastern region of Brazil, contains many bioactive compounds not yet exploited. Thus, this study evaluated the potential of pulps and peels of mature and semi-mature umbu as a source of bioactive compounds. Trigonelline contents ranged from 1.75 to 6.14 mg/100 g, values higher than those of many vegetables described in the literature, such as corn and barley. The contents of extractable and non-extractable phenolic compounds were also higher than those of other vegetables. Bioaccessibility of total extractable phenolics, flavonoids, and tannins was determined (15.67-37.73%, 31.87-39.10% and 18.81-114.27%, respectively). The constituent polysaccharides of the pulp and peel were tentatively chemically characterized as arabinoxylans, arabinogalactans, rhamnoarabinogalactans, xyloglucans, and pectin of the rhamnogalacturonan type. The technological potential of peel flours was evaluated. The maturation advancement showed no significant changes in the technological properties of the flours, except for color and water solubility index. Results indicated excellent prospects for future research on umbu pulps and peels as potential sources of natural bioactive compounds.
RESUMO
Aberrant microRNA expression implicates on hepatocellular carcinoma (HCC) development. Conversely, coffee consumption reduces by ~40% the risk for fibrosis/cirrhosis and HCC, while decaffeinated coffee does not. It is currently unknown whether these protective effects are related to caffeine (CAF), or to its combination with other common and/or highly bioavailable coffee compounds, such as trigonelline (TRI) and chlorogenic acid (CGA). We evaluated whether CAF individually or combined with TRI and/or CGA alleviates fibrosis-associated hepatocarcinogenesis, examining the involvement of miRNA profile modulation. Then, male C3H/HeJ mice were submitted to a diethylnitrosamine/carbon tetrachloride-induced model. Animals received CAF (50 mg/kg), CAF+TRI (50 and 25 mg/kg), CAF+CGA (50 and 25 mg/kg) or CAF+TRI+CGA (50, 25 and 25 mg/kg), intragastrically, 5×/week, for 10 weeks. Only CAF+TRI+CGA combination reduced the incidence, number and proliferation (Ki-67) of hepatocellular preneoplastic foci while enhanced apoptosis (cleaved caspase-3) in adjacent parenchyma. CAF+TRI+CGA treatment also decreased hepatic oxidative stress and enhanced the antioxidant Nrf2 axis. CAF+TRI+CGA had the most pronounced effects on decreasing hepatic pro-inflammatory IL-17 and NFκB, contributing to reduce CD68-positive macrophage number, stellate cell activation, and collagen deposition. In agreement, CAF+TRI+CGA upregulated tumor suppressors miR-144-3p, miR-376a-3p and antifibrotic miR-15b-5p, frequently deregulated in human HCC. CAF+TRI+CGA reduced the hepatic protein levels of pro-proliferative EGFR (miR-144-3p target), antiapoptotic Bcl-2 family members (miR-15b-5p targets), and the number of PCNA (miR-376a-3p target) positive hepatocytes in preneoplastic foci. Our results suggest that the combination of most common and highly bioavailable coffee compounds, rather than CAF individually, attenuates fibrosis-associated hepatocarcinogenesis by modulating miRNA expression profile.
Assuntos
Alcaloides/uso terapêutico , Anticarcinógenos/uso terapêutico , Cafeína/uso terapêutico , Carcinoma Hepatocelular/prevenção & controle , Ácido Clorogênico/uso terapêutico , Cirrose Hepática/complicações , Neoplasias Hepáticas/prevenção & controle , Animais , Carcinoma Hepatocelular/etiologia , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Cirrose Hepática/genética , Cirrose Hepática/patologia , Neoplasias Hepáticas/etiologia , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Masculino , Camundongos Endogâmicos C3H , MicroRNAs/genética , Transcriptoma/efeitos dos fármacosRESUMO
BACKGROUND: The relationships between soil and coffee beans variables were evaluated and then the influence of bean composition on cup quality attributes was computed by means of relation studies. A total of 139 coffee and soil samples were collected directly from the same number of coffee plantations in Chiapas, Mexico. RESULTS: In the elemental composition, only phosphorus, potassium, calcium, and copper in coffee beans had a significant (P < 0.05) relationship with the content of the same elements in soil. The level of macro- and microelements in the coffee bean affected some of the cup quality attributes, but variables such as texture, titratable acidity, and pH of water in soil had a major influence on those attributes. Caffeine, trigonelline, and 5-caffeoylquinic acid in green coffee beans also had a significant influence (P < 0.05) on the sensory attributes of the beverage. CONCLUSION: The elemental composition of soil and coffee beans was important in explaining the cup quality attributes, but the most important variables influencing the sensory quality of coffee were altitude of plantations and moisture of coffee beans. © 2020 Society of Chemical Industry.
Assuntos
Coffea/crescimento & desenvolvimento , Café/química , Sementes/química , Solo/química , Altitude , Cálcio/análise , Cálcio/metabolismo , Coffea/química , Coffea/metabolismo , Cobre/análise , Cobre/metabolismo , Qualidade dos Alimentos , Humanos , México , Fósforo/análise , Fósforo/metabolismo , Potássio/análise , Potássio/metabolismo , Sementes/crescimento & desenvolvimento , Sementes/metabolismo , PaladarRESUMO
The development of obesity-associated complications is related to various pathogenic events including chronic inflammation, oxidative stress and generation of advanced glycation end products (AGEs). Due to their antioxidant, anti-inflammatory and antiglycation properties, trigonelline and curcumin are interesting candidates to counteract complications of obesity and diabetes mellitus. The current study aimed to investigate the effects of treatment with curcumin or trigonelline mixed into yoghurt, alone or in combination, on mice fed high-fat diet (HFD); the focus was mainly on the potential of these phytochemicals to counteract oxidative and glycative stress. Yoghurt alone improved glucose tolerance and reduced proinflammatory cytokine levels in HFD mice; however, it did not affect the antioxidant status. Trigonelline-enriched yoghurt prevented fat accumulation in adipose tissue, improved both insulin sensitivity and glucose tolerance and exerted anti-inflammatory and antiglycation activities (reduced AGEs and AGE receptor levels and increased the levels of components related to AGE detoxification) in liver and kidney of HFD mice. Curcumin-enriched yoghurt exerted anti-inflammatory and potent antioxidant properties (increased antioxidant enzyme activities and decreased lipid peroxidation) in liver and kidney of HFD mice. However, several beneficial effects were nullified when trigonelline and curcumin were administered in combination. Trigonelline and curcumin have emerged as promising complementary therapy candidates for liver and kidney complications associated with obesity. However, the administration of these phytochemicals in combination, at least in HFD mice, was not effective; inhibition of biotransformation processes and/or the reaching of toxic doses during combined treatment may be prevailing over the individual pharmacodynamic actions of these phytochemicals.
Assuntos
Alcaloides/administração & dosagem , Curcumina/administração & dosagem , Glicosilação/efeitos dos fármacos , Inflamação/tratamento farmacológico , Obesidade/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , Animais , Antioxidantes/metabolismo , Biomarcadores/metabolismo , Glicemia/metabolismo , Peso Corporal , Dieta Hiperlipídica , Modelos Animais de Doenças , Quimioterapia Combinada , Glucose/metabolismo , Teste de Tolerância a Glucose , Homeostase , Rim/efeitos dos fármacos , Rim/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BLRESUMO
The study of Brazilian Conilon coffee genotypes with unknown chemical composition and sensory quality is extremely important since these data may contribute to the launching of new coffee cultivars in the international market with high cup quality. The present study aimed to investigate the metabolic profile of 3 genotypes of Conilon and compared them to Robusta Tropical and Arabica coffees, all collected at 3 different levels of ripeness. The extracts were analysed by ESI-LTQ-ORBITRAP, and 11 attributes were evaluated by sensory analysis. To correlate sensory, composition and maturation, chemometric analysis was used. The metabolites trigonelline, caffeine, caffeoylquinic acid and sugars revealed higher concentrations in genotypes 105 and 108. According to the sensorial analysis, genotype 108 showed the highest final score (82), which was even higher than the Arabica coffees. Among the new coffees studied, genotype 108 presented promising characteristics, sparking interest in its national and international commercialization.
Assuntos
Coffea/química , Genótipo , Alcaloides/análise , Brasil , Cafeína/análise , Coffea/genética , Genes de Plantas , Ácido Quínico/análogos & derivados , Ácido Quínico/análise , Sementes/química , Espectrometria de Massas por Ionização por ElectrosprayRESUMO
Recent meta-analyses indicate that coffee consumption reduces the risk for digestive tract (oral, esophageal, gastric and colorectal) and, especially, liver cancer. Coffee bean-derived beverages, as the widely-consumed espresso and "common" filtered brews, present remarkable historical, cultural and economic importance globally. These drinks have rich and variable chemical composition, depending on factors that vary from "seeding to serving". The alkaloids caffeine and trigonelline, as well as the polyphenol chlorogenic acid, are some of the most important bioactive organic compounds of these beverages, displaying high levels in both espresso and common brews and/or increased bioavailability after consumption. Thus, we performed a comprehensive literature overview of current knowledge on the effects of coffee beverages and their highly bioavailable compounds, describing: 1) recent epidemiological and experimental findings highlighting the beneficial effects against gastrointestinal/liver carcinogenesis, and 2) the main molecular mechanisms in these in vitro and in vivo bioassays. Findings predominantly address the protective effects of coffee beverages and their most common/bioavailable compounds individually on gastrointestinal and liver cancer development. Caffeine, trigonelline and chlorogenic acid modulate common molecular targets directly implicated in key cancer hallmarks, what could stimulate novel translational or population-based mechanistic investigations.
Assuntos
Cafeína/análise , Coffea/química , Café/química , Alcaloides/análise , Carcinogênese/efeitos dos fármacos , Ácido Clorogênico/análise , Neoplasias Gastrointestinais/prevenção & controle , Trato Gastrointestinal/efeitos dos fármacos , Trato Gastrointestinal/metabolismo , Humanos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Neoplasias Hepáticas/prevenção & controle , Metanálise como AssuntoRESUMO
Diabetes mellitus type 2 is a metabolic disorder characterized by chronic hyperglycemia, and an important cardiovascular risk factor with a high morbidity and mortality worldwide. Phytotherapy can be an useful complement in the treatment of chronic diseases, so the hypoglycemic effect of Bauhinia forficata (L) subsp. pruinosa (Fabaceae) was evaluated, as used in Chilean traditional medicine. The content of rutin (R) and trigonelline (T) in aqueous extracts (0.15 and 1.0 percent infusions) and lyophilized extract from leaves of B. forficata were determined by HPLC. It was obtained 2.80 ugR/mL and 2.87 ugT/mL for 0.15 percent infusion, 12.48 ugR/mL and 16.24 ugT/mL for 1.0 percent infusion, and 5.70 ugR/mL and 8.14 ugT/mL for the lyophilized extract (0.1percent). Subsequently, a pilot clinical study in diabetic and prediabetic volunteers (n = 15) was performed, taking one dose of the 0.15 percent infusion, three times a day after meals, for 3 months. The results showed a significant statistically reduction in percent of HbA1c of 0.57 +/- 0.83 (p = 0.0179), suggesting that the 0.15 percent infusion of B. forficata could be useful in the prevention or complementary treatment of diabetes...
La diabetes mellitus tipo 2 es una alteración metabólica caracterizada por hiperglicemia crónica, y un importante factor de riesgo cardiovascular con elevada morbimortalidad a nivel mundial. La Fitoterapia puede ser un complemento útil en el tratamiento de enfermedades crónicas, por lo que se evaluó el efecto hipoglicemiante de Bauhinia forficata (L) subsp. pruinosa (Fabaceae), según su uso en medicina tradicional Chilena. Se determinó mediante HPLC el contenido de rutina (R) y trigonelina (T) en infusos (0.15 por ciento y 1.0 por ciento) y extracto acuoso liofilizado de las hojas de B. forficata. Se obtuvo para el infuso 0.15 por ciento = 2.80 ugR/mL y 2.87 ugT/mL, infuso 1.0 por ciento = 12.48 ugR/mL y 16.24 ugT/mL, y en el extracto liofilizado 0.1 por ciento = 5.70 ugR/mL y 8.14 ugT/mL. Posteriormente, se realizó un estudio clínico piloto en voluntarios diabéticos y prediabéticos (n = 15), tomando una dosis del infuso al 0.15 por ciento, tres veces al día después de las comidas, durante 3 meses. Los resultados mostraron una reducción estadísticamente significativa del por ciento de HbA1c de 0.57 +/- 0.83 (p = 0.0179), sugiriendo que el infuso de hojas de B. forficata (0.15 por ciento) podría ser útil en la prevención o tratamiento complementario de la diabetes...
Assuntos
Humanos , Bauhinia/química , /tratamento farmacológico , Extratos Vegetais/administração & dosagem , Hipoglicemiantes/administração & dosagem , Alcaloides/análise , Cromatografia Líquida de Alta Pressão , Extratos Vegetais/química , Medicina Tradicional , Fitoterapia , Rutina/análiseRESUMO
Trigonelline (N-methylnicotinate) biosynthesized from nicotinate is one of the metabolically active pyridine alkaloid, widely distributed in plant kingdom. In the present study trigonelline has been isolated from various plant parts and callus cultures of Moringa oleifera Lam., Moringaceae, and was identified using TLC, GLC, GC-MS, which was comparable to that of the standard trigonelline. The trigonelline recovery was found to be maximum in the pods and minimum in flowers. In order to enhance the production of trigonelline in vitro grown cultures, different treatment doses of nicotinic acid (250, 500 and 750 mg L-1) were supplemented in the medium as precursor. Maximum increase (up to 1.10 fold) was observed in the treatment dose of 500 mg L-1 of nicotinic acid.
RESUMO
O processo de torração do café induz alterações físicas, químicas e sensoriais na matéria-prima, cuja intensidade e tipo dependem, principalmente, da composição química dos grãos e do tempo e temperatura utilizados na execução do mesmo. Este processo promove a degradação, formação e volatilização de vários compostos. Comercialmente, existem cafés torrados e moídos em diferentes pontos de torração, os quais originam bebidas com diferentes propriedades sensoriais e nutricionais. Os compostos trigonelina, ácidos clorogênicos e cafeína interferem no sabor e aroma do café. A trigonelina e os ácidos clorogênicos vêm sendo estudados também quanto ao aspecto nutricional, uma vez que esses compostos possuem ação benéfica à saúde. Esses compostos são solúveis em água quente, portanto, estarão presentes na bebida em função da sua estabilidade no processo de torração. Conduziu-se este trabalho, com o objetivo de avaliar as concentrações dos compostos trigonelina, ácidos clorogênicos e cafeína em cafés da espécie Coffea arabica L. classificados como bebida mole, dura e rio submetidos a três pontos de torração: claro, médio e escuro. As torrações mais acentuadas promoveram uma maior degradação de trigonelina e ácido 5-cafeoilquínico, enquanto que a torração clara promoveu degradação apenas para o ácido clorogênico, não interferindo nas concentrações de trigonelina. A degradação da cafeína não ocorreu em nenhum ponto de torração.
The roasting process of coffee induces sensorial, chemical and physical alterations in the raw material. The type and intensity of the process depend mainly on the chemical composition of the grains and on the time and temperature used. This process promotes the degradation, formation and volatilisation of several compounds. There are roast and ground coffees submitted to different roasting conditions available in the market, which give origin to beverages with different sensorial and nutritional properties. The compounds trigonelline, chlorogenic acids and caffeine interfere with the flavor of the coffee. The trigonelline and the chlorogenic acids were studied considering their nutritional aspect as well, since these compounds and"or their degradation products have a beneficial action to our health. These compounds are soluble in hot water therefore they will be present in the beverage depending on their stability through the roasting process. The aim of this work was to asses the concentrations of trigonelline, chlorogenic acids and caffeine in coffees of the species Coffea arabica, classified as soft, hard, and rio which were submitted to three roasting degrees: light, medium, and dark. The most intense roasting process generated a greater degradation of trigonelline and 5-caffeoilquinic (5-CQA) while the light roasting caused degradation just of the chlorogenic acid, not interfering with the trigonelline concentrations. Caffeine was not degraded at any roasting degree.
RESUMO
A rapid liquid chromatography-mass spectrometry method for the simultaneous quantification of caffeine, trigonelline, nicotinic acid and sucrose in coffee was developed and validated. The method involved extraction with hot water, clarification with basic lead acetate and membrane filtration, followed by chromatographic separation using a Spherisorb(®) S5 ODS2, 5µm chromatographic column and gradient elution with 0.3% aqueous formic acid/methanol at a flow rate of 0.2mL/min. The electrospray ionization source was operated in the negative mode to generate sucrose ions and in the positive mode to generate caffeine, trigonelline and nicotinic acid ions. Ionization suppression of all analytes was found due to matrix effect. Calibrations curves prepared in green and roasted coffee extracts were linear with r(2)>0.999. Roasted coffee was spiked and recoveries ranged from 93.0% to 105.1% for caffeine, from 85.2% to 116.2% for trigonelline, from 89.6% to 113.5% for nicotinic acid and from 94.1% to 109.7% for sucrose. Good repeatibilities (RSD<5%) were found for all analytes in the matrix. The limit of detection (LOD), calculated on the basis of signal-to-noise ratios of 3:1, was 11.9, 36.4, 18.5 and 5.0ng/mL for caffeine, trigonelline, nicotinic acid and sucrose, respectively. Analysis of 11 coffee samples (regular or decaffeinated green, ground roasted and instant) gave results in agreement with the literature. The method showed to be suitable for different types of coffee available in the market thus appearing as a fast and reliable alternative method to be used for routine coffee analysis.