In vitro simulated digestion and colonic fermentation of lychee pulp phenolics and their impact on metabolic pathways based on fecal metabolomics of mice

2021 ◽  
Author(s):  
Guitao Huang ◽  
Zhineng Wang ◽  
Guangxu Wu ◽  
Xuejiao Cao ◽  
Ruifen Zhang ◽  
...  
Keyword(s):  
Metabolic Pathways ◽  
Biochemical Change ◽  
Colonic Fermentation ◽  
Simulated Digestion

Biochemical change and bioactivities of lychee pulp phenolics following simulated human digestion and in vivo metabolism in mice.

scholarly journals Phosphatidylcholine Synthesis Influences the Diacylglycerol Homeostasis Required for Sec14p-dependent Golgi Function and Cell Growth

2001 ◽  
Vol 12 (3) ◽  
pp. 511-520 ◽  
Author(s):  
Annette L. Henneberry ◽  
Thomas A. Lagace ◽  
Neale D. Ridgway ◽  
Christopher R. McMaster
Keyword(s):  
Cell Death ◽  
Cell Growth ◽  
Phosphatidic Acid ◽  
Metabolic Pathways ◽  
Eukaryotic Cells ◽  
Kennedy Pathway ◽  
Phosphatidylcholine Synthesis ◽  
Long Chain

Phosphatidylcholine and phosphatidylethanolamine are the most abundant phospholipids in eukaryotic cells and thus have major roles in the formation and maintenance of vesicular membranes. In yeast, diacylglycerol accepts a phosphocholine moiety through aCPT1-derived cholinephosphotransferase activity to directly synthesize phosphatidylcholine. EPT1-derived activity can transfer either phosphocholine or phosphoethanolamine to diacylglcyerol in vitro, but is currently believed to primarily synthesize phosphatidylethanolamine in vivo. In this study we report that CPT1- and EPT1-derived cholinephosphotransferase activities can significantly overlap in vivo such that EPT1 can contribute to 60% of net phosphatidylcholine synthesis via the Kennedy pathway. Alterations in the level of diacylglycerol consumption through alterations in phosphatidylcholine synthesis directly correlated with the level of SEC14-dependent invertase secretion and affected cell viability. Administration of synthetic di8:0 diacylglycerol resulted in a partial rescue of cells fromSEC14-mediated cell death. The addition of di8:0 diacylglycerol increased di8:0 diacylglycerol levels 20–40-fold over endogenous long-chain diacylglycerol levels. Di8:0 diacylglcyerol did not alter endogenous phospholipid metabolic pathways, nor was it converted to di8:0 phosphatidic acid.

Bioaccessibility of Anthocyanins on in vitro Digestion Mmodels: Factors Implicated and Role in Functional Foods Development

2021 ◽  
Vol 28 ◽  
Author(s):  
Gabriel Prado ◽  
Isidora Pierattini ◽  
Guiselle Villarroel ◽  
Fernanda Fuentes ◽  
Alejandra Silva ◽  
...  
Keyword(s):  
Functional Foods ◽  
Raw Materials ◽  
Food Product ◽  
In Vitro Digestion ◽  
Raw Material ◽  
Simulated Digestion ◽  
Prevalence Of Obesity ◽  
Food Matrices

Background: Worldwide, the prevalence of obesity and related non-communicable chronic diseases is high and continues to grow. In that sense, anthocyanins (ANC) have shown beneficial health effects in preventing obesity and metabolic risk factors. Moreover, the demand for functional foods incorporating these compounds has risen significantly in the past years. Thus, there is a need for validations of the functional properties of these formulations; nevertheless, in vivo assays are complex and require a lot of resources. One approach for estimating bioactive compounds' functionality and health benefits is to evaluate their bioaccessibility on a specific food matrix, determined by various factors. This article aims to review different factors influencing the bioaccessibility of ANC evaluated on in vitro digestion models as a functionality parameter, elucidating the effect of chemical composition, raw materials, food matrices, and vehicles for the delivery of ANC. Methods: Study searches were performed using PubMed, Web of Science, Scopus, and Science Direct databases. Results: Different factors influenced bioaccessibility and stability of ANC studied by in vitro digestion which are: i) the raw material used for ANC obtention; ii) food processing; iii) other food components; iv) the extraction method and solvents used; v) the structure of ANC; vi) delivery system (e.g., microencapsulation); vii) pH of the medium; viii) the digestion stage. Conclusion: Simulated digestion systems allow to determine free or encapsulated ANC bioaccessibility in different food matrices, which offers advantages in determining the potential functionality of a food product.

scholarly journals Effects of indole-3-carbinol on metabolic parameters and on lipogenesis and lipolysis in adipocytes 182

2009 ◽  
Vol 54 (No. 4) ◽  
pp. 182-189 ◽  
Author(s):  
M. Okulicz ◽  
I. Hertig ◽  
J. Chichłowska
Keyword(s):  
Metabolic Pathways ◽  
Direct Action ◽  
Liver Steatosis ◽  
Density Lipoprotein ◽  
Metabolic Parameters ◽  
Male Rats ◽  
Liver Cholesterol ◽  
Carbohydrate And Lipid Metabolism

: Indole-3-carbinol (I3C) was found to have possible anticarcinogenic, antioxidant and anti-atherogenic effects on the organism. So far, its influence on metabolic pathways has been unknown. This work was the first attempt to determine the carbohydrate and lipid metabolism changes <I>in vivo</I> after administration of 150 mg/kg b.wt./day I3C to male rats. Additionally, the aim of this trial was to evaluate the direct effect of I3C on basal and hormone-induced lipogenesis and lipolysis in isolated rat adipocytes at concentrations 1, 10, 100 &mu;M <I>in vitro</I>. We can corroborate that adipocytes are susceptible to the direct action of I3C. The incubation of adipocytes with I3C at the three above-mentioned concentrations resulted in its influence on restriction of glucose entry into adipocytes in the basal as well as insulin-stimulated conditions. However, it was observed that I3C at these concentrations strongly intensified basic and epinephrine-stimulated lipolysis. I3C also has a significant influence on metabolism <I>in vivo</I>. Its administration to rats caused a significant increase in the content of triglycerides and a decrease in glycogen in the liver. The considerable augmentation of glucose, triglycerides, cholesterol in high-density lipoprotein and insulin with a concomitant decrease in FFA concentrations was noted in the blood serum. I3C did not alter phospholipids, total, free, esterified cholesterol in the serum and the liver cholesterol. The results obtained <I>in vivo</I> and <I>in vivo</I> indicate that the effect of I3C is adverse for the majority of metabolic parameters which were investigated. The most important finding in this study is the effect of I3C on liver steatosis and that the observed lower lipogenesis at higher lipolysis in fat cells may be involved in the mechanism.

scholarly journals In vivo efficacy and metabolism of the antimalarial cycleanine and improved in vitro antiplasmodial activity of novel semisynthetic analogues

2020 ◽  
Author(s):  
Fidelia Ijeoma Uche ◽  
Xiaozhen Guo ◽  
Jude Okokon ◽  
Imran Ullah ◽  
Paul Horrocks ◽  
...  
Keyword(s):  
Metabolic Pathways ◽  
High Performance ◽  
Antimalarial Activity ◽  
Biological Activities ◽  
Antiplasmodial Activity ◽  
Survival Times ◽  
Antiproliferative Effects ◽  
Future Evaluation

Bisbenzylisoquinoline (BBIQ) alkaloids are a diverse group of natural products that demonstrate a range of biological activities. In this study, the in vitro antiplasmodial activity of three BBIQ alkaloids (cycleanine (1), isochondodendrine (2) and 2′-norcocsuline (3)) isolated from the Triclisia subcordata Oliv. medicinal plant traditionally used for the treatment of malaria in Nigeria are studied alongside two semi-synthetic analogues (4 and 5) of cycleanine. The antiproliferative effects against a chloroquine-resistant Plasmodium falciparum strain were determined using a SYBR Green 1 fluorescence assay. The in vivo antimalarial activity of cycleanine (1) is then investigated in suppressive, prophylactic and curative murine malaria models after infection with a chloroquine-sensitive Plasmodium berghei strain. BBIQ alkaloids (1–5) exerted in vitro antiplasmodial activities with IC50 at low micromolar concentrations with the two semi-synthetic cycleanine analogues showing an improved potency and selectivity than cycleanine. At oral doses of 25 and 50mg/kg body weight of infected mice, cycleanine suppressed the levels of parasitaemia, and increased mean survival times significantly compared to the control groups. The metabolites and metabolic pathways of cycleanine (1) were also studied using high performance liquid chromatography electrospray ionization tandem mass spectrometry. Twelve novel metabolites were detected in rats after intragastic administration of cycleanine. The metabolic pathways of cycleanine were demonstrated to involve hydroxylation, dehydrogenation, and demethylation. Overall, these in vitro and in vivo results provide a basis for the future evaluation of cycleanine and its analogues as leads for further development.

scholarly journals Genomics Analysis of Metabolic Pathways of Human Stem Cell-Derived Microglia-Like Cells and the Integrated Cortical Spheroids

2019 ◽  
Vol 2019 ◽  
pp. 1-21 ◽  
Author(s):  
Julie Bejoy ◽  
Xuegang Yuan ◽  
Liqing Song ◽  
Thien Hua ◽  
Richard Jeske ◽  
...  
Keyword(s):  
Brain Tissue ◽  
Metabolic Pathways ◽  
Disease Modeling ◽  
Aerobic Glycolysis ◽  
Three Dimensional ◽  
Initiation Factor ◽  
Human Brain Tissue ◽  
P53 Signaling

Brain spheroids or organoids derived from human pluripotent stem cells (hiPSCs) are still not capable of completely recapitulating in vivo human brain tissue, and one of the limitations is lack of microglia. To add built-in immune function, coculture of the dorsal forebrain spheroids with isogenic microglia-like cells (D-MG) was performed in our study. The three-dimensional D-MG spheroids were analyzed for their transcriptome and compared with isogenic microglia-like cells (MG). Cortical spheroids containing microglia-like cells displayed different metabolic programming, which may affect the associated phenotype. The expression of genes related to glycolysis and hypoxia signaling was increased in cocultured D-MG spheroids, indicating the metabolic shift to aerobic glycolysis, which is in favor of M1 polarization of microglia-like cells. In addition, the metabolic pathways and the signaling pathways involved in cell proliferation, cell death, PIK3/AKT/mTOR signaling, eukaryotic initiation factor 2 pathway, and Wnt and Notch pathways were analyzed. The results demonstrate the activation of mTOR and p53 signaling, increased expression of Notch ligands, and the repression of NF-κB and canonical Wnt pathways, as well as the lower expression of cell cycle genes in the cocultured D-MG spheroids. This analysis indicates that physiological 3-D microenvironment may reshape the immunity of in vitro cortical spheroids and better recapitulate in vivo brain tissue function for disease modeling and drug screening.

Serum interspecies differences in metabolic pathways of bradykinin and [des-Arg9]BK: influence of enalaprilat

1996 ◽  
Vol 271 (4) ◽  
pp. H1340-H1347 ◽  
Author(s):  
A. Decarie ◽  
P. Raymond ◽  
N. Gervais ◽  
R. Couture ◽  
A. Adam
Keyword(s):  
Metabolic Pathways ◽  
Neutral Endopeptidase ◽  
Thrombin Inhibitor ◽  
Rat Serum ◽  
Highly Sensitive ◽  
Significant Difference ◽  
Hydrolysis Of

Among the different enzymes responsible for the metabolism of bradykinin (BK), three peptidases look relevant in vivo: kininase I (KI), which transforms BK into its active metabolite, [des-Arg9]BK; kininase II (KII); and neutral endopeptidase, which inactivate BK and [des-Arg9]BK. The in vitro incubation of BK and [des-Arg9]BK in the serum of four species with or without enalaprilat and the quantification of the immunoreactivity of both peptides at different time intervals allowed the measurement of the kinetic parameters characterizing their metabolic pathways. Highly sensitive chemiluminescent enzyme immunoassays were used to measure the residual concentrations of BK and [des-Arg9]BK. Half-life (t1/2) of BK showed significant difference among species: rats (10 +/- 1 s) = dogs (13 +/- 1 s) < rabbits (31 +/- 1 s) < humans (49 +/- 2 s). t1/2 values of [des-Arg9]BK were also species dependent: rats (96 +/- 6 s) < < rabbits (314 +/- 6 s) = dogs (323 +/- 11 s) = humans (325 +/- 12 s). Enalaprilat significantly prevented the rapid BK and [des-Arg9]BK degradation in all species except that of [des-Arg9]BK in rat serum. Relative amount of BK hydrolyzed by serum KII was given as follows: rabbits (93.7 +/- 14.8%) = rats (83.6 +/- 6.7%) = humans (76.0 +/- 7.5%) > dogs (50.0 +/- 3.9%). Its importance in the hydrolysis of [des-Arg9]BK was 5.2 +/- 0.5% in rats < < 33.9 +/- 1.5% in humans < 52.0 +/- 1.1% in rabbits < 65.1 +/- 3.4% in dogs. The participation of serum KI in the transformation of BK into [des-Arg9]BK was dogs (67.2 +/- 5.3%) > > humans (3.4 +/- 1.2%) = rabbits (1.8 +/- 0.2%) = rats (1.4 +/- 0.3%). Finally, no significant difference on t1/2 values for BK and [des-Arg9]BK could be demonstrated between serum and plasma treated with either sodium citrate or a thrombin inhibitor. These results revealed striking species differences in the serum metabolism of kinins that could address at least partially some of the controversial data related to the cardioprotective role of kinins.

Influence of stiripentol on cytochrome P450-mediated metabolic pathways in humans: In vitro and in vivo comparison and calculation of in vivo inhibition constants*

1997 ◽  
Vol 62 (5) ◽  
pp. 490-504 ◽  
Author(s):  
Agnès Tran ◽  
Elisabeth Rey ◽  
Gérard Pons ◽  
Marina Rousseau ◽  
Philippe d'Athis ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Metabolic Pathways ◽  
Inhibition Constants

scholarly journals Discovery of a novel stereospecific β-hydroxyacyl-CoA lyase/thioesterase shared by three metabolic pathways in Mycobacterium tuberculosis

2018 ◽  
Author(s):  
Hua Wang ◽  
Alexander A. Fedorov ◽  
Elena V. Fedorov ◽  
Deborah M. Hunt ◽  
Angela Rodgers ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Metabolic Pathways ◽  
Resistance Mechanism ◽  
Physiological Role ◽  
Vast Number ◽  
X Ray Crystallography ◽  
Leucine Catabolism ◽  
Orphan Enzyme

AbstractThe vast number of poorly characterised enzymes in Mycobacterium tuberculosis (Mtb) is one of the key barriers precluding a better understanding of the biology that underpins pathogenesis. Here, we investigated the Mtb orphan enzyme Rv2498c to delineate its physiological role. Our results from in vitro enzymatic assays, phylogenetic analysis, X-ray crystallography and in vivo Mtb experiments, de-orphan Rv2498c as a multi-functional β-hydroxyacyl-CoA lyase/thioesterase (β-HAClyase/thioesterase) that participates in three different metabolic pathways: L-leucine catabolism, itaconate dissimilation, and glyoxylate shunt. Moreover, the deletion of the rv2498c gene from the Mtb genome resulted in attenuation in the mouse model compared to infection with the parent strain. To the best of our knowledge, this is the first report of an (R)-3-hydroxyl-3-methylglutaryl-CoA for leucine catabolism and an itaconate-specific resistance mechanism in Mtb.

scholarly journals Multitargeted Effects of Vitexin and Isovitexin on Diabetes Mellitus and Its Complications

2021 ◽  
Vol 2021 ◽  
pp. 1-20
Author(s):  
Ibrahim Luru Abdulai ◽  
Samuel Kojo Kwofie ◽  
Winfred Seth Gbewonyo ◽  
Daniel Boison ◽  
Joshua Buer Puplampu ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Metabolic Pathways ◽  
Clinical Manifestations ◽  
In Vivo Studies ◽  
Technological Advancement ◽  
Application Research ◽  
One Stop ◽  
Product Chemistry

Background. Till date, there is no known antidote to cure diabetes mellitus despite the discovery and development of diverse pharmacotherapeutic agents many years ago. Technological advancement in natural product chemistry has led to the isolation of analogs of vitexin and isovitexin found in diverse bioresources. These compounds have been extensively studied to explore their pharmacological relevance in diabetes mellitus. Aim of the Study. The present review was to compile results from in vitro and in vivo studies performed with vitexin and isovitexin derivatives relating to diabetes mellitus and its complications. A systematic online literature query was executed to collect all relevant articles published up to March 2020. Results. In this piece, we have collected data and presented it in a one-stop document to support the multitargeted mechanistic actions of vitexin and isovitexin in controlling diabetes mellitus and its complications. Conclusion. Data collected hint that vitexin and isovitexin work by targeting diverse pathophysiological and metabolic pathways and molecular drug points involved in the clinical manifestations of diabetes mellitus. This is expected to provide a deeper understanding of its actions and also serve as a catapult for clinical trials and application research.

scholarly journals OCT4 induces embryonic pluripotency via STAT3 signaling and metabolic mechanisms

2021 ◽  
Vol 118 (3) ◽  
pp. e2008890118
Author(s):  
Giuliano G. Stirparo ◽  
Agata Kurowski ◽  
Ayaka Yanagida ◽  
Lawrence E. Bates ◽  
Stanley E. Strawbridge ◽  
...  
Keyword(s):  
Metabolic Pathways ◽  
Developmental Stages ◽  
Early Mouse Embryo ◽  
Stat3 Signaling ◽  
Quantitative Immunofluorescence ◽  
Early Mouse ◽  
Rate Limiting ◽  
Molecular Circuitry

OCT4 is a fundamental component of the molecular circuitry governing pluripotency in vivo and in vitro. To determine how OCT4 establishes and protects the pluripotent lineage in the embryo, we used comparative single-cell transcriptomics and quantitative immunofluorescence on control and OCT4 null blastocyst inner cell masses at two developmental stages. Surprisingly, activation of most pluripotency-associated transcription factors in the early mouse embryo occurs independently of OCT4, with the exception of the JAK/STAT signaling machinery. Concurrently, OCT4 null inner cell masses ectopically activate a subset of trophectoderm-associated genes. Inspection of metabolic pathways implicates the regulation of rate-limiting glycolytic enzymes by OCT4, consistent with a role in sustaining glycolysis. Furthermore, up-regulation of the lysosomal pathway was specifically detected in OCT4 null embryos. This finding implicates a requirement for OCT4 in the production of normal trophectoderm. Collectively, our findings uncover regulation of cellular metabolism and biophysical properties as mechanisms by which OCT4 instructs pluripotency.

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