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Echinacea purpurea L. (EP) preparations are globally popular herbal supplements known for their medicinal benefits, including anti-inflammatory activities, partly related to their phenolic composition. However, regarding their use for the management of inflammation-related intestinal diseases, the knowledge about the fate of orally ingested constituents throughout the human gastrointestinal tract and the exposition of in vitro digested extracts in relevant inflammatory models are unknown. This study investigated for the first time the impact of in vitro gastrointestinal digestion (INFOGEST) on the phenolic composition and anti-inflammatory properties of EP extracts from flowers (EF), leaves (EL), and roots (ER) on IL-1ß-treated human colon-derived CCD-18Co cells. Among the seven hydroxycinnamic acids identified using HPLC-UV-MS/MS, chicoric and caftaric acids showed the highest concentrations in EL, followed by EF and ER, and all extracts exerted significant reductions in IL-6, IL-8, and PGE2 levels. After digestion, despite reducing the bioaccessibility of their phenolics, the anti-inflammatory effects were preserved for digested EL and, to a lesser extent, for EF, but not for digested ER. The lower phenolic content in digested EF and ER could explain these findings. Overall, this study emphasizes the potential of EP in alleviating intestinal inflammatory conditions and related disorders.
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Echinacea , Espectrometria de Massas em Tandem , Humanos , Extratos Vegetais/farmacologia , Folhas de Planta , Anti-Inflamatórios/farmacologia , ColoRESUMO
OBJECTIVE: Hyperintensity signal in T2-weighted magnetic resonance imaging (MRI) has been related to better therapeutic response during pasireotide treatment in acromegaly. The aim of the study was to evaluate T2 MRI signal intensity and its relation with pasireotide therapeutic effectiveness in real-life clinical practice. DESIGN, PATIENTS AND MEASUREMENTS: Retrospective multicentre study including acromegaly patients treated with pasireotide. Adenoma T2-weighted MRI signal at diagnosis was qualitatively classified as iso-hyperintense or hypointense. Insulin-like growth factor (IGF-I), growth hormone (GH) and tumour volume reduction were assessed after 6 and 12 months of treatment and its effectiveness evaluated according to baseline MRI signal. Hormonal response was considered 'complete' when normalization of IGF-I levels was achieved. Significant tumour shrinkage was defined as a volume reduction of ≥25% from baseline. RESULTS: Eighty-one patients were included (48% women, 50 ± 1.5 years); 93% had previously received somatostatin receptor ligands (SRLs) treatment. MRI signal was hypointense in 25 (31%) and hyperintense in 56 (69%) cases. At 12 months of follow-up, 42/73 cases (58%) showed normalization of IGF-I and 37% both GH and IGF-I. MRI signal intensity was not associated with hormonal control. 19/51 cases (37%) presented a significant tumour volume shrinkage, 16 (41%) from the hyperintense group and 3 (25%) from the hypointense. CONCLUSIONS: T2-signal hyperintensity was more frequently observed in pasireotide treated patients. Almost 60% of SRLs resistant patients showed a complete normalization of IGF-I after 1 year of pasireotide treatment, regardless of the MRI signal. There was also no difference in the percentage tumour shrinkage over basal residual volume between the two groups.
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Acromegalia , Adenoma , Hormônio do Crescimento Humano , Humanos , Feminino , Masculino , Acromegalia/tratamento farmacológico , Acromegalia/diagnóstico , Fator de Crescimento Insulin-Like I/metabolismo , Adenoma/complicações , Adenoma/diagnóstico por imagem , Adenoma/tratamento farmacológico , Hormônio do Crescimento Humano/uso terapêutico , Imageamento por Ressonância Magnética/métodos , Resultado do Tratamento , Octreotida/uso terapêuticoRESUMO
Despite researchers' and clinicians' exponential understanding of chronic diseases' complexity, ranging from cancer, diabetes, and neurodegenerative disorders, we still have a lot of unanswered questions on pathobiology mechanisms, wherein inflammation is central [...].
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Cognição , Diabetes Mellitus , Humanos , InflamaçãoRESUMO
Traumatic brain injury (TBI) remains one of the leading causes of death and disability in young adults worldwide. Despite growing evidence and advances in our knowledge regarding the multifaceted pathophysiology of TBI, the underlying mechanisms, though, are still to be fully elucidated. Whereas initial brain insult involves acute and irreversible primary damage to the brain, the processes of subsequent secondary brain injury progress gradually over months to years, providing a window of opportunity for therapeutic interventions. To date, extensive research has been focused on the identification of druggable targets involved in these processes. Despite several decades of successful pre-clinical studies and very promising results, when transferred to clinics, these drugs showed, at best, modest beneficial effects, but more often, an absence of effects or even very harsh side effects in TBI patients. This reality has highlighted the need for novel approaches that will be able to respond to the complexity of the TBI and tackle TBI pathological processes on multiple levels. Recent evidence strongly indicates that nutritional interventions may provide a unique opportunity to enhance the repair processes after TBI. Dietary (poly)phenols, a big class of compounds abundantly found in fruits and vegetables, have emerged in the past few years as promising agents to be used in TBI settings due to their proven pleiotropic effects. Here, we give an overview of the pathophysiology of TBI and the underlying molecular mechanisms, followed by a state-of-the-art summary of the studies that have evaluated the efficacy of (poly)phenols administration to decrease TBI-associated damage in various animal TBI models and in a limited number of clinical trials. The current limitations on our knowledge concerning (poly)phenol effects in TBI in the pre-clinical studies are also discussed.
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Lesões Encefálicas Traumáticas , Neoplasias Encefálicas , Animais , Fenóis/uso terapêutico , Encéfalo/patologia , Modelos Animais , Neoplasias Encefálicas/patologiaRESUMO
Pheochromocytomas and paragangliomas (PPGLs) provide some of the clearest genetic evidence for the critical role of metabolism in the tumorigenesis process. Approximately 40% of PPGLs are caused by driver germline mutations in 16 known susceptibility genes, and approximately half of these genes encode members of the tricarboxylic acid (TCA) cycle. Taking as a starting point the involvement of the TCA cycle in PPGL development, we aimed to identify unreported mutations that occurred in genes involved in this key metabolic pathway and that could explain the phenotypes of additional individuals who lack mutations in known susceptibility genes. To accomplish this, we applied a targeted sequencing of 37 TCA-cycle-related genes to DNA from 104 PPGL-affected individuals with no mutations in the major known predisposing genes. We also performed omics-based analyses, TCA-related metabolite determination, and 13C5-glutamate labeling assays. We identified five germline variants affecting DLST in eight unrelated individuals (â¼7%); all except one were diagnosed with multiple PPGLs. A recurrent variant, c.1121G>A (p.Gly374Glu), found in four of the eight individuals triggered accumulation of 2-hydroxyglutarate, both in tumors and in a heterologous cell-based assay designed to functionally evaluate DLST variants. p.Gly374Glu-DLST tumors exhibited loss of heterozygosity, and their methylation and expression profiles are similar to those of EPAS1-mutated PPGLs; this similarity suggests a link between DLST disruption and pseudohypoxia. Moreover, we found positive DLST immunostaining exclusively in tumors carrying TCA-cycle or EPAS1 mutations. In summary, this study reveals DLST as a PPGL-susceptibility gene and further strengthens the relevance of the TCA cycle in PPGL development.
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Aciltransferases/genética , Neoplasias das Glândulas Suprarrenais/genética , Mutação em Linhagem Germinativa , Paraganglioma/genética , Feocromocitoma/genética , Adulto , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Carcinogênese , Domínio Catalítico , Ciclo do Ácido Cítrico , Metilação de DNA , Feminino , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Predisposição Genética para Doença , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Perda de Heterozigosidade , Masculino , Pessoa de Meia-IdadeRESUMO
A large number of epidemiological studies have shown that consumption of fruits, vegetables, and beverages rich in (poly)phenols promote numerous health benefits from cardiovascular to neurological diseases. Evidence on (poly)phenols has been applied mainly to flavonoids, yet the role of phenolic acids has been largely overlooked. Such phenolics present in food combine with those resulting from gut microbiota catabolism of flavonoids and chlorogenic acids and those produced by endogenous pathways, resulting in large concentrations of low molecular weight phenolic metabolites in human circulation. Independently of the origin, in human intervention studies using diets rich in (poly)phenols, a total of 137 low molecular weight phenolic metabolites have been detected and quantified in human circulation with largely unknown biological function. In this review, we will pinpoint two main aspects of the low molecular weight phenolic metabolites: (i) the microbiota responsible for their generation, and (ii) the analysis (quali- and quantitative) in human circulation and their respective pharmacokinetics. In doing so, we aim to drive scientific advances regarding the ubiquitous roles of low molecular weight phenolic metabolites using physiologically relevant concentrations and under (patho)physiologically relevant conditions in humans.
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Dieta , Fenóis , Flavonoides/metabolismo , Frutas , Humanos , Peso MolecularRESUMO
Breast cancer (BC) is the most common malignancy and the leading cause of cancer-related death in adult women worldwide. Over 85% of BC cases are non-hereditary, caused by modifiable extrinsic factors related to lifestyle, including dietary habits, which play a crucial role in cancer prevention. Although many epidemiological and observational studies have inversely correlated the fruit and vegetable consumption with the BC incidence, the involvement of their phenolic content in this correlation remains contradictory. During decades, wrong approaches that did not consider the bioavailability, metabolism, and breast tissue distribution of dietary phenolics persist behind the large currently existing gap between preclinical and clinical research. In the present review, we provide comprehensive preclinical and clinical evidence according to physiologically relevant in vitro and in vivo studies. Some dietary phenolics such as resveratrol (RSV), quercetin, isoflavones, epigallocatechin gallate (EGCG), lignans, and curcumin are gaining attention for their chemopreventive properties in preclinical research. However, the clinical evidence of dietary phenolics as BC chemopreventive compounds is still inconclusive. Therefore, the only way to validate promising preclinical results is to conduct clinical trials in BC patients. In this regard, future perspectives on dietary phenolics and BC research are also critically discussed.
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Anticarcinógenos/uso terapêutico , Neoplasias da Mama/prevenção & controle , Quimioprevenção/métodos , Suplementos Nutricionais , Flavonoides/uso terapêutico , Fenóis/uso terapêutico , Animais , Anticarcinógenos/farmacocinética , Disponibilidade Biológica , Neoplasias da Mama/epidemiologia , Ensaios Clínicos como Assunto , Dieta , Modelos Animais de Doenças , Feminino , Flavonoides/farmacocinética , Humanos , Incidência , Fenóis/farmacocinéticaRESUMO
Recently, the development of functional beverages has been enhanced to promote health and nutritional well-being. Thus, the fermentation of plant foods with lactic acid bacteria can enhance their antioxidant capacity and others like anti-inflammatory activity, which may depend on the variations in the total content and profile of (poly)phenols. The present study aimed to investigate the impact of fermentation with two strains of Lactiplantibacillus plantarum of several herbal infusions from thyme, rosemary, echinacea, and pomegranate peel on the (poly)phenolic composition and whether lacto-fermentation can contribute to enhance their in vitro antioxidant and anti-inflammatory effects on human colon myofibroblast CCD18-Co cells. HPLC-MS/MS analyses revealed that fermentation increased the content of the phenolics present in all herbal infusions. In vitro analyses indicated that pomegranate infusion showed higher antioxidant and anti-inflammatory effects, followed by thyme, echinacea, and rosemary, based on the total phenolic content. After fermentation, despite increasing the content of phenolics, the antioxidant and anti-inflammatory effects via reduction pro-inflammatory markers (IL-6, IL-8 and PGE2) were similar to those of their corresponding non-fermented infusions, with the exception of a greater reduction in lacto-fermented thyme. Overall, the findings suggest that the consumption of lacto-fermented herbal infusions could be beneficial in alleviating intestinal inflammatory disorders.
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Management of inflammatory bowel disease (IBD) poses significant challenges, and there is a need for innovative therapeutic approaches. This study investigates the anti-inflammatory properties of the dietary sesquiterpene lactone (SL) 11ß,13-dihydrolactucin, which can be found in chicory, in three distinct complementary models of intestinal inflammation (two cell models and a zebrafish model), offering comprehensive insights into its potential application for IBD treatment alternatives. In a triple cell co-culture composed of Caco-2, HT29-MTX-E12, and Raji B, 11ß,13-dihydrolactucin demonstrated remarkable anti-inflammatory activity at several levels of the cellular inflammatory response. Notably, 11ß,13-dihydrolactucin prevented the activation of critical signalling pathways associated with inflammation, namely NF-κB and MAPK p38. This SL also decreased the release of the neutrophil-recruiting chemokine IL-8. Additionally, the compound reduced the gene expression of IL-6 and TNF-α, as well as the gene and protein expression of the inflammatory inducible enzymes iNOS and COX-2. In a myofibroblast-like human cell model, 11ß,13-dihydrolactucin decreased the release of the cytokine TNF-α and the COX-2-derived inflammation mediator PGE2. Finally, in a zebrafish model of gut inflammation, 11ß,13-dihydrolactucin effectively reduced neutrophil infiltration, further supporting its anti-inflammatory efficacy in a physiological context. Collectively, our findings highlight the promising anti-inflammatory potential of 11ß,13-dihydrolactucin across various facets of intestinal inflammation, providing a foundation for the consideration of chicory as a promising candidate for incorporation in food or nutraceutical products for the potential prevention of IBD.
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INTRODUCTION: Growth hormone (GH)-secreting pituitary tumors (GHomas) are the most common acromegaly cause. At diagnosis, most of them are macroadenomas, and up to 56% display cavernous sinus invasion. Biomarker assessment associated with tumor growth and invasion is important to optimize their management. OBJECTIVES: The study aims to identify clinical/hormonal/molecular biomarkers associated with tumor size and invasiveness in GHomas and to analyze the influence of pre-treatment with somatostatin analogs (SSAs) or dopamine agonists (DAs) in key molecular biomarker expression. METHODS: Clinical/analytical/radiological variables were evaluated in 192 patients from the REMAH study (ambispective multicenter post-surgery study of the Spanish Society of Endocrinology and Nutrition). The expression of somatostatin/ghrelin/dopamine system components and key pituitary/proliferation markers was evaluated in GHomas after the first surgery. Univariate/multivariate regression studies were performed to identify association between variables. RESULTS: Eighty percent of patients harbor macroadenomas (63.8% with extrasellar growth). Associations between larger and more invasive GHomas with younger age, visual abnormalities, higher IGF1 levels, extrasellar/suprasellar growth, and/or cavernous sinus invasion were found. Higher GH1 and lower PRL/POMC/CGA/AVPR1B/DRD2T/DRD2L expression levels (P < .05) were associated with tumor invasiveness. Least Absolute Shrinkage and Selection Operator's penalized regression identified combinations of clinical and molecular features with areas under the curve between 0.67 and 0.82. Pre-operative therapy with DA or SSAs did not alter the expression of any of the markers analyzed except for DRD1/AVPR1B (up-regulated with DA) and FSHB/CRHR1 (down-regulated with SSAs). CONCLUSIONS: A specific combination of clinical/analytical/molecular variables was found to be associated with tumor invasiveness and growth capacity in GHomas. Pre-treatment with first-line drugs for acromegaly did not significantly modify the expression of the most relevant biomarkers in our association model. These findings provide valuable insights for risk stratification and personalized management of GHomas.
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Acromegalia , Adenoma , Adenoma Hipofisário Secretor de Hormônio do Crescimento , Invasividade Neoplásica , Humanos , Masculino , Feminino , Acromegalia/metabolismo , Pessoa de Meia-Idade , Adulto , Adenoma Hipofisário Secretor de Hormônio do Crescimento/patologia , Adenoma Hipofisário Secretor de Hormônio do Crescimento/metabolismo , Adenoma/metabolismo , Adenoma/patologia , Idoso , Agonistas de Dopamina/uso terapêutico , Biomarcadores Tumorais/metabolismo , Somatostatina/análogos & derivados , Somatostatina/uso terapêutico , Hormônio do Crescimento Humano/metabolismoRESUMO
The Aryl Hydrocarbon Receptor (AHR) is a ligand-dependent transcription factor able to control complex transcriptional processes in several cell types, which has been correlated with various diseases, including inflammatory bowel diseases (IBD). Numerous studies have described different compounds as ligands of this receptor, like xenobiotics, natural compounds, and several host-derived metabolites. Dietary (poly)phenols have been studied regarding their pleiotropic activities (e.g., neuroprotective and anti-inflammatory), but their AHR modulatory capabilities have also been considered. However, dietary (poly)phenols are submitted to extensive metabolism in the gut (e.g., gut microbiota). Thus, the resulting gut phenolic metabolites could be key players modulating AHR since they are the ones that reach the cells and may exert effects on the AHR throughout the gut and other organs. This review aims at a comprehensive search for the most abundant gut phenolic metabolites detected and quantified in humans to understand how many have been described as AHR modulators and what could be their impact on inflammatory gut processes. Even though several phenolic compounds have been studied regarding their anti-inflammatory capacities, only 1 gut phenolic metabolite, described as AHR modulator, has been evaluated on intestinal inflammatory models. Searching for AHR ligands could be a novel strategy against IBD.
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Microbioma Gastrointestinal , Doenças Inflamatórias Intestinais , Humanos , Receptores de Hidrocarboneto Arílico/metabolismo , Inflamação , Regulação da Expressão GênicaRESUMO
Sesquiterpene lactones - such as those found in chicory - are considered promising bioactive compounds. These small molecules have shown several health benefits for various diseases, including brain disorders. However, it is unknown whether these compounds can cross the blood-brain barrier (BBB), and which could be the effects on brain microvascular endothelial cells. We show that six sesquiterpene lactones evaluated in an in vitro model of the BBB have different capacities to be transported through the barrier. Costunolide presented more than 20 % of transport while lactucin, 11ß-13-dihydrolactucin, 11ß-13-dihydrolactucopicrin, and parthenolide presented between 10 % and 20 %, whilst almost no transport was detected for lactucopicrin. Furthermore, costunolide and parthenolide reduced P-gp ABC transporter expression alongside an increase in caveolin-1, the main protein of caveolae. Remarkably, these two compounds improved barrier tightness by increasing the expression of both tight and adherens junctions. These findings open a new avenue to explore costunolide and parthenolide as promising compounds for brain therapies.
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Barreira Hematoencefálica , Sesquiterpenos , Barreira Hematoencefálica/metabolismo , Células Endoteliais/metabolismo , Lactonas/farmacologia , Sesquiterpenos/farmacologiaRESUMO
Current knowledge indicates that the consumption of isoflavone-rich foodstuffs can have a beneficial impact on cardiovascular health. To what extent these isoflavones act as the main actors of that benefit is less clear. Genistein (GEN), daidzein (DAZ), and the DAZ-derived microbial metabolite equol (Eq) exhibit antiangiogenic effects in vitro, but their low bloodstream concentrations make it difficult to rationalize the in vivo effects. Their derived phase-II metabolites (glucuronides and sulfates) are major metabolites found in plasma, but their role as antiangiogenic molecules remains unexplored. We aimed here to first assess the anti-angiogenic activities of the main circulating isoflavone metabolites (glucuronides and sulfates) and compare them with their corresponding free forms at physiological concentrations (0.1-10 µM). The effects of the conjugated vs. free forms on tubulogenesis, cell migration, and VEGF-induced signalling were investigated in primary human aortic endothelial cells (HAECs). While (R,S)-equol 7-ß-D-glucuronide (Eq 7-glur) exerted dose-dependent inhibition of tubulogenesis and endothelial migration comparable to that exerted by the free forms (GEN, DAZ, and Eq), the rest of the phase-II conjugates exhibited no significant effects. The underlying molecular mechanisms were independent of the bFGF but related to the modulation of the VEGF pathway. Besides, the observed dissimilar cellular metabolism (conjugation/deconjugation) places the phase-II metabolites as precursors of the free forms; however, the question of whether this metabolism impacts their biological activity requires additional studies. These new insights suggest that isoflavones and their circulating metabolites, including Eq 7-glur, may be involved in cardiovascular health (e.g., targeting angiogenesis).
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Angiogenesis is a complex process encompassing endothelial cell proliferation, migration, and tube formation. While numerous studies describe that curcumin exerts antitumor properties (e.g., targeting angiogenesis), information regarding other dietary curcuminoids such as demethoxycurcumin (DMC) and bisdemethoxycurcumin (BisDMC) is scant. In this study, we evaluated the antiangiogenic activities of these three curcuminoids at physiological concentrations (0.1-5 µM) on endothelial cell migration and tubulogenesis and the underlying associated mechanisms on human aortic endothelial cells (HAECs). Results showed that the individual compounds and a representative mixture inhibited the tubulogenic and migration capacity of endothelial cells dose-dependently, while sparing cell viability. Notably, DMC and BisDMC at 0.1 and 1 µM showed higher capacity than curcumin inhibiting tubulogenesis. These compounds also reduced phosphorylation of the VEGFR2 and the downstream ERK and Akt pathways in VEGF165-stimulated cells. In silico analysis showed that curcuminoids could bind the VEGFR2 antagonizing the VEGF-mediated angiogenesis. These findings suggest that physiologically concentrations of curcuminoids might counteract pro-angiogenic stimuli relevant to tumorigenic processes.
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Diarileptanoides , Neovascularização Patológica , Receptor 2 de Fatores de Crescimento do Endotélio Vascular , Inibidores da Angiogênese/farmacologia , Movimento Celular , Proliferação de Células , Curcumina/uso terapêutico , Diarileptanoides/metabolismo , Diarileptanoides/farmacologia , Diarileptanoides/uso terapêutico , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Neovascularização Patológica/tratamento farmacológico , Fator A de Crescimento do Endotélio Vascular/efeitos dos fármacos , Fator A de Crescimento do Endotélio Vascular/metabolismo , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/efeitos dos fármacos , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismoRESUMO
Exosomes are extracellular vesicles (EVs) that regulate intercellular signaling by transferring small RNAs, proteins, nucleic acids, lipids, and other metabolites to local or distant organs, including the brain, by crossing the blood-brain barrier. However, the transport of (poly)phenols in human EVs has not yet been described. Therefore, we aimed here to explore (i) whether resveratrol and (or) its derived metabolites are found in the cargo of human plasma exosome-containing EVs (E-EVs), (ii) when this incorporation occurs, and (iii) whether resveratrol intake stimulates the release of E-EVs. Thus, in a pharmacokinetic study, healthy volunteers (n = 16) consumed 1 capsule (420 mg resveratrol) in the evening before attending the clinic and one more capsule on the day of the pharmacokinetics. The plasma and the isolated E-EVs were analyzed using UPLC-ESI-QTOF-MS. Of 17 metabolites in the plasma, 9 were identified in the E-EVs, but not free resveratrol. The kinetic profiles of resveratrol metabolites were similar in the plasma and the E-EVs, a higher metabolite concentration being detected in the plasma than in the E-EVs. However, the plasma/E-EVs ratio decreased in the gut microbial metabolites, suggesting their better encapsulation efficiency in E-EVs. In addition, glucuronide conjugates of resveratrol, dihydroresveratrol, and lunularin were incorporated into the E-EVs more efficiently than their corresponding sulfates despite glucuronides reaching lower plasma concentrations. Notably, more E-EVs were detected 10 h after resveratrol consumption. This exploratory study provides the first evidence that (i) resveratrol metabolites are transported by E-EVs, with a preference for glucuronide vs. sulfates, (ii) the gut microbial metabolites concentration and kinetic profiles are closely similar in E-EVs and plasma, and (iii) resveratrol intake elicits E-EVs secretion. Overall, these results open new research avenues on the possible role of E-EVs in (poly)phenol health effects.
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Exossomos , Vesículas Extracelulares , Exossomos/metabolismo , Vesículas Extracelulares/metabolismo , Glucuronídeos/metabolismo , Humanos , Resveratrol , SulfatosRESUMO
SARS-CoV-2 is a highly transmissible and pathogenic coronavirus causing a respiratory disease that emerged in 2019, leading to a public health emergency situation which continues to date. The treatment options are still very limited and vaccines available are less effective against new variants. SARS-CoV-2 enzymes, namely main protease (Mpro) and papain-like protease (PLpro), play a pivotal role in the viral life cycle, making them a putative drug target. Here, we described for the first time the potential inhibitory activity of chicory extract against both proteases. Besides, we have identified that the four most abundant sesquiterpene lactones in chicory inhibited these proteases, showing an effective binding in the active sites of Mpro and PLpro. This paper provides new insight for further drug development or food-based strategies for the prevention of SARS-CoV-2 by targeting viral proteases.
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Tratamento Farmacológico da COVID-19 , Cichorium intybus , Sesquiterpenos , Cichorium intybus/química , Cichorium intybus/metabolismo , Humanos , Lactonas/farmacologia , Peptídeo Hidrolases/metabolismo , SARS-CoV-2 , Sesquiterpenos/química , Sesquiterpenos/farmacologia , Replicação ViralRESUMO
Previous studies have shown that a resistant dextrin soluble fibre has prebiotic properties with related health benefits on blood glucose management and satiety. Our aim was to demonstrate the effects of continuous administration of resistant dextrin on intestinal gas production, digestive sensations, and gut microbiota metabolism and composition. Healthy subjects (n = 20) were given resistant dextrin (14 g/d NUTRIOSE®, Roquette Frères, Lestrem, France) for four weeks. Outcomes were measured before, at the beginning, end, and two weeks after administration: anal evacuations of gas during daytime; digestive perception, girth, and gas production in response to a standard meal; sensory and digestive responses to a comfort meal; volume of colonic biomass by magnetic resonance; taxonomy and metabolic functions of fecal microbiota by shotgun sequencing; metabolomics in urine. Dextrin administration produced an initial increase in intestinal gas production and gas-related sensations, followed by a subsequent decrease, which magnified after discontinuation. Dextrin enlarged the volume of colonic biomass, inducing changes in microbial metabolism and composition with an increase in short chain fatty acids-producing species and modulation of bile acids and biotin metabolism. These data indicate that consumption of a soluble fibre induces an adaptative response of gut microbiota towards fermentative pathways with lower gas production.
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Dextrinas , Microbiota , Humanos , Dextrinas/farmacologia , Intestinos , Prebióticos , Fezes , HomeostaseRESUMO
Urolithins, metabolites produced by the gut microbiota from the polyphenols ellagitannins and ellagic acid, are discovered by the research group in humans almost 20 years ago. Pioneering research suggests urolithins as pleiotropic bioactive contributors to explain the health benefits after consuming ellagitannin-rich sources (pomegranates, walnuts, strawberries, etc.). Here, this study comprehensively updates the knowledge on urolithins, emphasizing the review of the literature published during the last 5 years. To date, 13 urolithins and their corresponding conjugated metabolites (glucuronides, sulfates, etc.) have been described and, depending on the urolithin, detected in different human fluids and tissues (urine, blood, feces, breastmilk, prostate, colon, and breast tissues). There has been a substantial advance in the research on microorganisms involved in urolithin production, along with the compositional and functional characterization of the gut microbiota associated with urolithins metabolism that gives rise to the so-called urolithin metabotypes (UM-A, UM-B, and UM-0), relevant in human health. The design of in vitro studies using physiologically relevant assay conditions (molecular forms and concentrations) is still a pending subject, making some reported urolithin activities questionable. In contrast, remarkable progress has been made in the research on the safety, bioactivity, and associated mechanisms of urolithin A, including the first human interventions.
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Microbioma Gastrointestinal , Juglans , Masculino , Humanos , Microbioma Gastrointestinal/fisiologia , Cumarínicos/farmacologia , Cumarínicos/metabolismo , Taninos Hidrolisáveis/farmacologia , Taninos Hidrolisáveis/metabolismo , Fezes , Ácido ElágicoRESUMO
The intake of hesperidin-rich sources, mostly found in orange juice, can decrease cardiometabolic risk, potentially linked to the gut microbial phase-II hesperetin derivatives. However, the low hesperidin solubility hampers its bioavailability and microbial metabolism, yielding a high inter-individual variability (high vs. low-producers) that prevents consistent health-related evidence. Contrarily, the human metabolism of (lemon) eriocitrin is hardly known. We hypothesize that the higher solubility of (lemon) eriocitrin vs. (orange) hesperidin might yield more bioavailable metabolites than hesperidin. A randomized-crossover human pharmacokinetic study (n = 16) compared the bioavailability and metabolism of flavanones from lemon and orange extracts and postprandial changes in oxidative, inflammatory, and metabolic markers after a high-fat-high-sugars meal. A total of 17 phase-II flavanone-derived metabolites were identified. No significant biomarker changes were observed. Plasma and urinary concentrations of all metabolites, including hesperetin metabolites, were higher after lemon extract intake. Total plasma metabolites showed significantly mean lower Tmax (6.0 ± 0.4 vs. 8.0 ± 0.5 h) and higher Cmax and AUC values after lemon extract intake. We provide new insights on hesperetin-eriodictyol interconversion and naringenin formation from hesperidin in humans. Our results suggest that regular consumption of a soluble and eco-friendly eriocitrin-rich lemon extract could provide a circulating concentration metabolites threshold to exert health benefits, even in the so-called low-producers.