scholarly journals The Metabolomic-Gut-Clinical Axis of Mankai Plant-Derived Dietary Polyphenols

Nutrients ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1866
Author(s):  
Anat Yaskolka Yaskolka Meir ◽  
Kieran Tuohy ◽  
Martin von von Bergen ◽  
Rosa Krajmalnik-Brown ◽  
Uwe Heinig ◽  
...  
Keyword(s):  
Mediterranean Diet ◽  
Aquatic Plant ◽  
Environmental Stressors ◽  
Bacterial Gene ◽  
Dietary Polyphenols ◽  
Urolithin A ◽  
Trial Participants ◽  
Clinical Trial Methods

Background: Polyphenols are secondary metabolites produced by plants to defend themselves from environmental stressors. We explored the effect of Wolffia globosa ‘Mankai’, a novel cultivated strain of a polyphenol-rich aquatic plant, on the metabolomic-gut clinical axis in vitro, in-vivo and in a clinical trial. Methods: We used mass-spectrometry-based metabolomics methods from three laboratories to detect Mankai phenolic metabolites and examined predicted functional pathways in a Mankai artificial-gut bioreactor. Plasma and urine polyphenols were assessed among the 294 DIRECT-PLUS 18-month trial participants, comparing the effect of a polyphenol-rich green-Mediterranean diet (+1240 mg/polyphenols/day, provided by Mankai, green tea and walnuts) to a walnuts-enriched (+440 mg/polyphenols/day) Mediterranean diet and a healthy controlled diet. Results: Approximately 200 different phenolic compounds were specifically detected in the Mankai plant. The Mankai-supplemented bioreactor artificial gut displayed a significantly higher relative-abundance of 16S-rRNA bacterial gene sequences encoding for enzymes involved in phenolic compound degradation. In humans, several Mankai-related plasma and urine polyphenols were differentially elevated in the green Mediterranean group compared with the other groups (p < 0.05) after six and 18 months of intervention (e.g., urine hydroxy-phenyl-acetic-acid and urolithin-A; plasma Naringenin and 2,5-diOH-benzoic-acid). Specific polyphenols, such as urolithin-A and 4-ethylphenol, were directly involved with clinical weight-related changes. Conclusions: The Mankai new plant is rich in various unique potent polyphenols, potentially affecting the metabolomic-gut-clinical axis.

The Role of Polyphenols in the Modulation of Plasma Non-Enzymatic Antioxidant Capacity (NEAC)

2012 ◽  
Vol 82 (3) ◽  
pp. 228-232 ◽  
Author(s):  
Mauro Serafini ◽  
Giuseppa Morabito
Keyword(s):  
Antioxidant Capacity ◽  
Dietary Intervention ◽  
Ex Vivo ◽  
The Body ◽  
Dietary Polyphenols ◽  
Enzymatic Antioxidant ◽  
Endogenous Antioxidant

Dietary polyphenols have been shown to scavenge free radicals, modulating cellular redox transcription factors in different in vitro and ex vivo models. Dietary intervention studies have shown that consumption of plant foods modulates plasma Non-Enzymatic Antioxidant Capacity (NEAC), a biomarker of the endogenous antioxidant network, in human subjects. However, the identification of the molecules responsible for this effect are yet to be obtained and evidences of an antioxidant in vivo action of polyphenols are conflicting. There is a clear discrepancy between polyphenols (PP) concentration in body fluids and the extent of increase of plasma NEAC. The low degree of absorption and the extensive metabolism of PP within the body have raised questions about their contribution to the endogenous antioxidant network. This work will discuss the role of polyphenols from galenic preparation, food extracts, and selected dietary sources as modulators of plasma NEAC in humans.

scholarly journals Isolation and structural elucidation of dimeric epigallocatechin-3-gallate autoxidation products and their antioxidant capacity

2021 ◽  
Author(s):  
Julian Alfke ◽  
Uta Kampermann ◽  
Svetlana Kalinina ◽  
Melanie Esselen
Keyword(s):  
Antioxidant Capacity ◽  
Antioxidant Properties ◽  
Cd Spectroscopy ◽  
Trolox Equivalent Antioxidant Capacity ◽  
Published Data ◽  
Dietary Polyphenols ◽  
Cellular Effects ◽  
The Impact

AbstractDietary polyphenols like epigallocatechin-3-gallate (EGCG)—which represents the most abundant flavan-3-ol in green tea—are subject of several studies regarding their bioactivity and health-related properties. On many occasions, cell culture or in vitro experiments form the basis of published data. Although the stability of these compounds is observed to be low, many reported effects are directly related to the parent compounds whereas the impact of EGCG degradation and autoxidation products is not yet understood and merely studied. EGCG autoxidation products like its dimers theasinensin A and D, “P2” and oolongtheanin are yet to be characterized in the same extent as their parental polyphenol. However, to investigate the bioactivity of autoxidation products—which would minimize the discrepancy between in vitro and in vivo data—isolation and structure elucidation techniques are urgently needed. In this study, a new protocol to acquire the dimers theasinensin A and D as well as oolongtheanin is depicted, including a variety of spectroscopic and quadrupole time-of-flight high-resolution mass spectrometric (qTOF-HRMS) data to characterize and assign these isolates. Through nuclear magnetic resonance (NMR) spectroscopy, polarimetry, and especially circular dichroism (CD) spectroscopy after enzymatic hydrolysis the complementary atropisomeric stereochemistry of the isolated theasinensins is illuminated and elucidated. Lastly, a direct comparison between the isolated EGCG autoxidation products and the monomer itself is carried out regarding their antioxidant properties featuring Trolox equivalent antioxidant capacity (TEAC) values. These findings help to characterize these products regarding their cellular effects and—which is of special interest in the flavonoid group—their redox properties.

Plant polyphenols: free radical scavengers or chain-breaking antioxidants?

1995 ◽  
Vol 61 ◽  
pp. 103-116 ◽  
Author(s):  
Catherine Rice-Evans
Keyword(s):  
Biological Effects ◽  
Relative Effectiveness ◽  
Antioxidant Properties ◽  
Peroxyl Radicals ◽  
Free Radical Scavengers ◽  
Dietary Polyphenols ◽  
Chain Breaking ◽  
Lipid Peroxyl Radicals

There is increasing interest in the biological effects of tea- and wine-derived polyphenols and many studies in vitro and in vivo are demonstrating their antioxidant properties. Tea is a major source of dietary polyphenols and an even richer source of the flavanols, the catechins and catechin/gallate esters. Although there are limited studies on the bioavailability of the polyphenols, the absorption of flavanols in humans has been shown. The studies described in this chapter discuss the relative antioxidant potentials of the polyphenolic flavonoids in vitro against radicals generated in the aqueous phase in comparison with their relative effectiveness as antioxidants against propagating lipid peroxyl radicals, and how their activity influences that of α-tocopherol in low-density lipoproteins exposed to oxidative stress.

scholarly journals Interactions between CYP3A4 and Dietary Polyphenols

2015 ◽  
Vol 2015 ◽  
pp. 1-15 ◽  
Author(s):  
Loai Basheer ◽  
Zohar Kerem
Keyword(s):  
Critical Role ◽  
Negative Consequences ◽  
Cytochrome P450 Enzymes ◽  
Dietary Polyphenols ◽  
Complex Interactions ◽  
Human Cytochrome ◽  
Clinical Consequences

The human cytochrome P450 enzymes (P450s) catalyze oxidative reactions of a broad spectrum of substrates and play a critical role in the metabolism of xenobiotics, such as drugs and dietary compounds. CYP3A4 is known to be the main enzyme involved in the metabolism of drugs and most other xenobiotics. Dietary compounds, of which polyphenolics are the most studied, have been shown to interact with CYP3A4 and alter its expression and activity. Traditionally, the liver was considered the prime site of CYP3A-mediated first-pass metabolic extraction, butin vitroandin vivostudies now suggest that the small intestine can be of equal or even greater importance for the metabolism of polyphenolics and drugs. Recent studies have pointed to the role of gut microbiota in the metabolic fate of polyphenolics in human, suggesting their involvement in the complex interactions between dietary polyphenols and CYP3A4. Last but not least, all the above suggests that coadministration of drugs and foods that are rich in polyphenols is expected to stimulate undesirable clinical consequences. This review focuses on interactions between dietary polyphenols and CYP3A4 as they relate to structural considerations, food-drug interactions, and potential negative consequences of interactions between CYP3A4 and polyphenols.

scholarly journals Hair cortisol concentration differs across site and person: localization and consistency of responses to a brief pain stressor

2010 ◽  
pp. 979-983 ◽  
Author(s):  
CF Sharpley ◽  
KG Kauter ◽  
JR McFarlane
Keyword(s):  
Environmental Stressors ◽  
Hair Cortisol ◽  
Before And After ◽  
Animal Hair ◽  
Cortisol Responses ◽  
Collection Period ◽  
Few Data ◽  
Ice Water

Although in vitro studies have shown that cortisol concentrations in human and animal hair respond to environmental stressors, few data have been reported regarding the in vivo variability of hair cortisol to brief pain stressors. As an extension of a previous study, hair was collected and assayed for cortisol concentrations from each of three sites (elbow, mid-forearm, wrist) before and after participants immersed their hand in ice water for 1 min. Results showed that the “localization” boundary of hair cortisol responses previously reported was able to be reduced to only 250 mm between sites. Furthermore, all participants showed considerable variability in hair cortisol across the three sites at each collection period, although consistency across participants in overall responsivity of hair cortisol to the pain stressor was observed.

scholarly journals Introducing Gordonibacter urolithinfaciens into Gut Ecosystems to Study Its Role in Mediating the Metabolic Benefits of Dietary Polyphenols

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 1594-1594
Author(s):  
Ashley Toney ◽  
Yibo Xian ◽  
Jing Shao ◽  
Robert Schmaltz ◽  
Virginia Chaidez ◽  
...  
Keyword(s):  
Drinking Water ◽  
Ellagic Acid ◽  
Improve Insulin Sensitivity ◽  
Microbial Conversion ◽  
Dietary Polyphenols ◽  
Funding Sources ◽  
Host Metabolism

Abstract Objectives Dietary polyphenols such as ellagitannins undergo microbial conversion to yield urolithins, which improve insulin sensitivity. However, feeding ellagic acid-containing foods sometimes yields variable levels of metabolic improvements in humans, suggesting that some individuals may not harbor the specific microbes responsible for transforming ellagic acid (EA) into urolithins. One species of gut bacteria, Gordonibacter urolithinfaciens (G. uro), has been shown to convert EA into urolithins in vitro. However, the specific role of G. uro in mediating the metabolic benefits of EA-containing foods in vivo is unknown, in part, because of challenges associated with its engraftment in mouse models. This study aimed to determine whether G. uro could be introduced into an established microbiota as a single dose or daily probiotic to facilitate future studies regarding its role in improving host metabolism via conversion of EA to urolithins. Methods Germ-free (GF) C57BL/6 mice were either: (1) mono-associated with G. uro for 2 wks prior to introduction of one of three conventional mouse microbiotas naturally deficient for G. uro, (2) colonized with both G. uro and a conventional G. uro-deficient microbiota together, (3) colonized with a conventional G. uro-deficient microbiota for 2 wks and then given a single oral gavage of G. uro, or (4) colonized with a conventional G. uro-deficient microbiota for 2 wks and then administered G. uro fresh daily in drinking water. Results G. uro successfully monocolonized a previously GF mouse but was not detectable following introduction of a complex G. uro-deficient microbiota. G. uro also failed to persist when GF mice were first colonized with a conventional G. uro-deficient microbiota and then given a single gavage of G. uro. However, ex-GF mice colonized with a complex G. uro-deficient microbiota and given daily doses of G. uro in their drinking water were able to maintain this organism throughout the study. Conclusions Our studies demonstrate the challenges associated with introducing G. uro into a microbiota even when G. uro is provided prior to microbiota establishment and the microbiota is naturally devoid of G. uro. These results suggest that G. uro may need to be administered as a daily probiotic to provide health benefits to individuals unable to convert ellagic acid foods into beneficial urolithins. Funding Sources USDA NIFA.

Spatiotemporal control of the bacteria to express interferon-γ by focused ultrasound for tumor immunotherapy

2021 ◽  
Author(s):  
Yuhao Chen ◽  
Meng Du ◽  
Zhen Yuan ◽  
Fei Yan ◽  
Zhiyi Chen
Keyword(s):  
Focused Ultrasound ◽  
Tumor Therapy ◽  
Tumor Immunotherapy ◽  
Interferon Γ ◽  
Genetic Switch ◽  
Bacterial Gene ◽  
Bacterial Gene Expression ◽  
Ifn Γ

Abstract Bacteria-based tumor therapy has recently attracted wide attentions due to its unique capability in targeting tumors and preferentially colonizing the core area of the tumor. Various therapeutic genes were also harbored into these engineering bacteria to enhance their anti-tumor efficacy. However, it is difficult to spatiotemporally control the expression of these inserted genes in the tumor site. Here, we engineered an ultrasound-responsive bacterium (URB) which can induce the expression of exogenous genes in an ultrasound-controllable manner. Owing to the advantage of ultrasound in the tissue penetration, energy focusing into heating, an acoustic remote control of bacterial gene expression can be realized by designing a temperature-actuated genetic switch. Cytokine interferon-γ (IFN-γ), an important immune regulatory molecule that plays a significant role in tumor immunotherapy, was used to test the system. Our results showed a brief hyperthermia by focused ultrasound successfully induced the expression of IFN-γ gene, significantly improving anti-tumor efficacy of URB in vitro and in vivo. Our study provided a novel strategy for bacteria-mediated tumor immunotherapy.

Polyphenols: Anti-Platelet Nutraceutical?

2018 ◽  
Vol 24 (2) ◽  
pp. 146-157 ◽  
Author(s):  
Valeria Ludovici ◽  
Jens Barthelmes ◽  
Matthias P. Nagele ◽  
Andreas J. Flammer ◽  
Isabella Sudano
Keyword(s):  
Platelet Aggregation ◽  
Platelet Activation ◽  
Therapeutic Potential ◽  
Critical Role ◽  
Organ Damage ◽  
Low Grade ◽  
Protective Effects ◽  
Dietary Polyphenols

Background: Coronary artery disease (CAD) is a disease progressing over many years. Genetic factors, as well as the exposure to risk factors, are continuously leading to endothelial dysfunction, vascular alterations and, eventually, organ damage, major cardiovascular events and deaths. Oxidative stress, platelet hyperactivity and low-grade inflammation are important modulators in this context, contributing to plaque formation. Since platelet activation plays a critical role in the development and progression of atherothrombotic events, the inhibition of platelet hyperactivity may contribute to decreased atherothrombotic risk. The consumption of bioactive foods, and plant-derived polyphenols in particular, might impart anti-thrombotic and cardiovascular protective effects. Methods: Aim of this work is to focus on the potential of dietary derived polyphenols to reduce platelet hyperactivity or hypercoagulability in addition to discussing their possible complementary anti-platelet therapeutic potential. All the relevant publications on this topic were systematically reviewed. Results: Various studies demonstrated that polyphenol supplementation affects platelet aggregation and function in vitro and in vivo, mainly neutralizing free radicals, inhibiting platelet activation and related signal transduction pathways, blocking thromboxane A2 receptors and enhancing nitric oxide production. Experimental data concerning the effect of dietary polyphenols on platelet aggregation in vivo are poor, and results are often conflicting. Only flavanols clearly mirrored in vivo showed the efficacy in vitro in modulating platelet function. Conclusion: Dietary polyphenols, and above all flavanols contained in cocoa and berries, reduce platelet activation and aggregation via multiple pathways. However, more controlled interventional studies are required to establish which doses are required as well as what circulating concentrations are sufficient to induce functional antiplatelet effects.

scholarly journals Diet-Derived Polyphenol Metabolite Enterolactone Is a Tissue-Specific Estrogen Receptor Activator

Endocrinology ◽  
2007 ◽  
Vol 148 (10) ◽  
pp. 4875-4886 ◽  
Author(s):  
Pauliina Penttinen ◽  
Jan Jaehrling ◽  
Anastasios E. Damdimopoulos ◽  
José Inzunza ◽  
Josephine G. Lemmen ◽  
...  
Keyword(s):  
Gene Expression ◽  
Ligand Binding ◽  
Estrogenic Activity ◽  
Culture Conditions ◽  
Mouse Uterus ◽  
Tissue Specific ◽  
Dietary Polyphenols ◽  
Reporter Mice

Numerous dietary compounds can modify gene expression by binding to the members of the nuclear receptor superfamily of transcription factors. For example, dietary polyphenols, such as soy isoflavones genistein and daidzein, modulate the activity of the estrogen receptors (ERs)-α and ERβ. An additional class of dietary polyphenols that modulate cellular signaling pathways are lignans, compounds that are common constituents of Western diets. In this study, we show that a metabolite of dietary lignans, enterolactone, at physiological concentrations, activates ER-mediated transcription in vitro with preference for ERα. The effects of enterolactone are mediated by the ER ligand binding domain and are susceptible to antiestrogen treatment. Furthermore, the affinity of enterolactone toward ERα, measured by a novel ligand binding assay, is augmented in cell culture conditions. Moreover, our results demonstrate for the first time that enterolactone has estrogenic activity in vivo. In transgenic estrogen-sensitive reporter mice, enterolactone induces tissue-specific estrogen-responsive reporter gene expression as well as promotes uterine stromal edema and expression of estrogen-responsive endogenous genes (CyclinD1 and Ki67). Taken together, our data show that enterolactone is a selective ER agonist inducing ER-mediated transcription both in vitro in different cell lines and in vivo in the mouse uterus.

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